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Author and friend R.T. Kendall eulogizes the life of prophetic minister John Paul Jackson, who passed away in February from cancer. read more
Ministry Leadership
More articles in Ministry Leadership
- Why Conviction Matters in the Life of a Prophet
- Flood of Aberrant Doctrines Endangering True Faith
- How to Give a Church Prophetic Correction
- John Eckhardt: Understanding the Office of the Prophet
- Perry Stone: How to Judge a Prophetic Word
- Could Bonnke's Prophetic Declaration Spark a Great Awakening?
Here Is Perhaps the Greatest Failing of Godly Pastor-Husbands
If all pastors would learn to do this, personal scandals in the church might be a thing of the past.
Become The Leader God Intended You To Be!
For Christian leadership insights and inspiration follow Dr. Steve Greene's Blog, Greenelines.
Effective Leaders Confront Quickly
Don't let it build up for a blow-up.
9 Traits of 'Mean' Churches
What can we do to become a more unified body? How can churches demonstrate more positive ...
4 Ways People Are Fact-Checking Your Preaching
Have you noticed that fewer people are bringing their Bibles to church, but are using a smartphone ...
5 Reasons a Church or Organization Stops Growing
Is your church vigorously exploring this issue, or do you continue to maintain the status quo?
12 Earmarks of a True Apostolic Movement
There is a global apostolic movement that is shaking Christianity and expanding the church as never ...
7 Things the Church Can't Do for the Pastor
You may have the greatest church of your ministry career, but regardless of how wonderful the ...
20 Tips From a Church That is Exploding With Growth
This church in Alabama has got it going, and God's blessing it with tremendous growth and an ...
4 Types of Unconnected People and How to Connect With Them
Here's how to identify these people and how you can engage them.
Become The Leader God Intended You To Be!
For Christian leadership insights and inspiration follow Dr. Steve Greene's Blog, Greenelines.
7 Suggestions for Challenging a Controlling Leader
Authority should be respected, but there are times when it is appropriate to confront it. Jesus ...
6 Tips for Pastors Who Struggle With People-Pleasing Guilt
You know you can't be there for every member of your congregation every time. Here are some ...
3 Ways Pastors Should Respond to Criticism
Criticism is simply part of the job when it comes to pastoring. Here's how you can deal with it.
5 Characteristics of 'Country Club' Christians
Do you know of any in your congregation who simply treat church as a place to come and fellowship ...
10 Joy Stealers in Ministry and How to Get It Back
What are some joy stealers you have encountered in ministry? How did you get your joy back?
Great Leaders Don't Seek Perfection
You must count the costs in pursuit of excellence.
What Is Everyone Talking About?
Influential leaders ask more questions and make fewer statements.
Kingdom Economics: Equipped but Not Participating
Isn't one of our responsibilities as ministers to equip the saints where they are lacking and ...
7 Reasons Your Students Aren't Sharing Their Faith
These seven obstacles to your teens sharing their faith can be removed if you are willing to ...
Saddleback Church Commemorates 35 Years of Ministry and Growth
Started with seven people in Rick and Kay Warren's living room, here's how Saddleback has ...
How to Tap Into Unrealized Potential in the Kingdom
In this week's Kingdom Economics, James Russell reveals why saints have unlimited potential ...

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5:01 pm
Mon January 25, 2010
Police and City Talks Update
By KWGS News
Tulsa, OK – The City and the Public Safety Unions are attempting to work out agreements on wage concessions. Mayor Bartlett gave some insight into the city's latest police proposal.
The offer includes NO lay-offs. However, the plan does calls for a five-point-two percent pay cut that would be extended beyond this year.
If the deal is not acceptable to the Union and its rank and file, 155-officers have been told they will be laid-off on Friday.


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Super quick delivery as always Planet X rocks!!!
Does as it says
Service was OK I was notified how the build of the half-customised bike is progressing, shipment was well trackable and package arrived _almost_ undamaged. The goods inside were fine, though. No complaints about the service so far.
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Good for the size and price
Grear product
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Perfect as a throw in the bag backup light.
Good cheap light for the kids bike, and can be fitted to the front fork as opposed to the handlebars which is handy on my daughters bike.
Bought for the kids bikes. Perfect for what I needed them to do and very cheap.
Easy to fit and bright enough to help be seen
Cheap but does the job expected
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Great light, great price.
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Xmas present so cant really conment
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great little back up light, not strong enough for forrest riding, but there when batteries die in my main lights
Haven't used them for much but the service and quality of goods means Iwill use them more in future
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Not that bright but what was I expecting?
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one of the LED bulbs didn't work - will try a replacement
Flashy flashy and small
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Got it finished
grammypAugust 27, 2011
The baby shower is tomorrow at 1 and I finished the quilt about an hour ago. Not fancy, but I'm pleased. I quilted the darks so the lights will puff when washed. At least that is the plan. I'll try to get pictures after it is washed to see if it works.
I gotta get my camera checked out. The colors are really much nicer than in the pictures. Not sure why they are so yellow.


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Russian Christians Celebrate 1000th Birthday
By Editorial Staff
Published May 1, 1988
In the midst of the pomp and fanfare of the 1000th birthday of Christianity in Russia, the younger generation in the Soviet Union is apparently showing a growing interest in spiritual matters. "There has been a religious revival among young people," said Deputy Chief Father Vladimir of the Russian Orthodoxy's main monastic center.
Young Russians are increasingly interested in joining the clergy, according to Time magazine, and they are attending church in unprecedented numbers. For example, at a monastery that re-opened as a church after a period of government control, two-fifths of the congregation is in their 20's and 30's.
This growing interest in Christianity among the youth during the state-sanctioned celebration may stem from boredom, disillusionment, and cynicism – which the Soviet government is acknowleging as a problem.
Jon Utley, associate editor of The Times of Americas magazine and commentator on Voice of America, said that Soviet youth are a major government concern. Utley recently went on a tour sponsored by the World Media Association with 50 journalists, academic leaders, and activists.
"From talking to young people, we could well understand why Soviet youth are a major preoccupation of the government. There were almost no diversions. Our members (when alone) were often approached by youths for black market transactions."
Utley attended a press conference by the Foreign Ministry. During the briefing, Communist state officials distributed a release which stated: "Young people are uncompromising in their search for truth. One can't overlook the fact that many young people during the years of stagnation reconciled themselves to the hopelessness of attempts to attain truth and change …"
"(T)hey saw in society elements that were totally incompatible with what they knew about the nature of socialism. The example of some officials … was morally destructive." Specifics on these officials were not revealed.
Utley also attended a meeting in Leningrad with students of the Soviet American Friendship Society. "In one discussion about human rights, a student said that Russia should withdraw from Afghanistan and was promptly answered and dressed down for 10 minutes by an older member," he said in a report on his visit in Human Events.
Besides growing interest among youth, the official Russian Orthodox Church is becoming more vocal in the Soviet press and television on matters involving the country's moral and cultural climate. "Glasnost and religious freedom are intimately correlated," Vsevold Marinov told The Forerunner. Marinov is the director of the Soviet Bureau of Opinion based in Moscow. "Religious people have much more of a voice in the mass media which wasn't the case before."
Marinov is also a member of the Peace Committee, a delegation of Soviet citizens that recently visited the U.S. Pravda Cultural Editor Nikolai Potopov agreed, saying, "Religious people are more and more active in sharing their opinions with non-religious people on peace-related problems. Confiscated church buildings are being returned to churches."
To commemorate the birth of Christianity, the Soviet government gave permission to the United Bible Society in Stuttgart, West Germany, for the importation of 100,000 Ukranian language Bibles. But many church leaders both inside and outside the country say that Gorbachev's reconstructionist policies are cosmetic, and are calling for more radical changes to be made in Soviet dealings with the Church. Father Gleb Yakunin, an ex-prisoner who initiated the Russian Orthodox human rights movement in 1965, said, "The general atmosphere has changed a lot, but when it comes to actual church life, it's like it was 30 years ago."
Communist officials have said there may be signs of a new policy toward state control of churches. In the communist Central Committee Publication, an article stated, "The time has finally come to put an end to a suspicious and unfavorable attitude toward believers and their ideals of care for people, love and moral self-improvement. We should take into account the unprecedented historical fact that the church has managed to find its place in socialist society without detriment to its faith."
Yuri Smirnov, spokesman for the Council for Religious Affairs, told Time, "The church could be a help in changing people's attitudes toward work. There are too many divorces. There are many other social problems, like drug abuse. There are three to eight suicides among young people in Moscow every week. Why not use the power of the Church, since millions of people are under its influence?"
This is most definitely a far cry from the rhetoric of past Soviet regimes, which predicted total eradication of faith and Christianity by this date. As millions of nationals celebrate the arrival of the Christian gospel in the Soviet Union, and as young people return to the churches in record numbers, it will most likely open the doors for even more lively discussion in the Kremlin about the future of the USSR.
Forerunner - Home » The Forerunner Newspaper » Russia, Ukraine and former USSR
Your comments are welcome!
The Silent Scream (DVD) Eight Languages
"When the lives of the unborn are snuffed out, they often feel pain, pain that is long and agonizing." – President Ronald Reagan to National Religious Broadcasters Convention, January 1981
Ronald Reagan became convinced of this as a result of watching The Silent Scream – a movie he considered so powerful and convicting that he screened it at the White House.
The modern technology of real-time ultrasound now reveals the actual responses of a 12-week old fetus to being aborted. As the unborn child attempts to escape the abortionist's suction curette, her motions can be seen to become desperately agitated and her heart rate doubles. Her mouth opens – as if to scream – but no sound can come out. Her scream doesn't have to remain silent, however … not if you will become her voice. This newly re-mastered version features eight language tracks and two bonus videos.
"…a high technology "Uncle Tom's Cabin" arousing public opinion just as Harriet Beecher Stowe's 1852 antislavery novel ignited the abolitionist movement." – Sen. Gordon Humphrey, Time Magazine
Languages: English, Spanish, French, South Korean, Chinese, Russian, Portuguese, Japanese
Running Time: 28 minutes
$17.95 — ORDER NOW!(We accept all major credit cards and PayPal.)
Click here for more information
Dr. Francis Schaeffer - A Christian Manifesto (DVD)
That Swiss Hermit Strikes Again!
Dr. Schaeffer, who was one of the most influential Christian thinkers in the twentieth century, shows that secular humanism has displaced the Judeo-Christian consensus that once defined our nation's moral boundaries. Law, education, and medicine have all been reshaped for the worse as a consequence. America's dominant worldview changed, Schaeffer charges, when Christians weren't looking.
Schaeffer lists two reasons for evangelical indifference: a false concept of spirituality and fear. He calls on believers to stand against the tyranny and moral chaos that come when humanism reigns-and warns that believers may, at some point, be forced to make the hard choice between obeying God or Caesar. A Christian Manifesto is a thought-provoking and bracing Christian analysis of American culture and the obligation Christians have to engage the culture with the claims of Christ.
$19.95 — ORDER NOW!(We accept all major credit cards and PayPal.)
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Abortion Clinic 911 Calls (DVD)
Exposes the Dangers of Abortion to Women!
These shocking eyewitness accounts expose the dangers of abortion not only to unborn children, but to the health and lives women as well. An antidote to the smokescreens of the liberal media, these short clips show what really happens in and around abortion clinics.
Although the content is emotionally gut-wrenching, these videos have been used in church seminars and small groups to educate Christians on the abortion issue and to lead people toward a pro-life position. Contains 2 hours and 40 minutes of materials that can be shown separately.
Watch these pro-life videos on-line.
"These videos helped change my mind from pro-choice to pro-life. Your videos are what did it for me. I will be walking in next year's March For Life in San Francisco." — A. Jackson, California
"I was going to have an abortion until I saw your video. Praise Jesus!"
— M. Drew, YouTube Commenter
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Martin Luther: Digitally Remastered 1953 Classic (DVD)
"Here I stand … I can do no other!"
With these immortal words, an unknown German monk sparked a spiritual revolution that changed the world.
The dramatic classic film of Martin Luther's life was released in theaters worldwide in the 1950s and was nominated for two Oscars. A magnificent depiction of Luther and the forces at work in the surrounding society that resulted in his historic reform efforts, this film traces Luther's life from a guilt-burdened monk to his eventual break with the Roman Catholic Church.
Running time: 105 minutes
Special offer: Order 5 or more for $5 each.
Watch a clip from Martin Luther.
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Dr. Francis Schaeffer - How Should We Then Live? (DVD)
Special Two-Disc Set!
After 40 years of intense study and world-wide ministry, Dr. Francis Schaeffer completed his crowning work of scholarship – to present profound truths in simple film language. Dr. Schaeffer's brilliant analysis of the past and predictions for current trends have proven so uncannily accurate that this amazing series still feels contemporary almost three decades after its initial release. Ultimately, Schaeffer concludes that man's only hope is a return to God's Biblical absolute, the truth revealed in Christ through the Scriptures.
Available for the first time on DVD, this documentary spectacular also includes intimate in-depth conversations with Francis and Edith Schaeffer. With the on-disc study guide, this presentation forms a unique course of comprehensive study. While this series forms an innovative analysis of the past, this outstanding work is more than history. Each episode focuses on a significant era, yet speaks clearly to 21st-century man with answers for modern problems.
$49.95 — ORDER NOW!(We accept all major credit cards and PayPal.)


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Aerial photos show Minnesota 60 progress in Worthington
The following photos of Minnesota 60 construction were provided to the Daily Globe last week by the Worthington Composite Squadron of the Civil Air Patrol.
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- About the College
- Departments & Offices
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H1N1 Outbreak Puts College Experts in the News
With dozens of years of experience in research swine flu and avian flu, respectively, Dr. Mo Saif and Dr. Richards Slemons, both professors in the Department of Veterinary Preventive Medicine, were sought-after experts in explaining the recent outbreak of H1N1. Dr. Saif is also the director of the Food Animal Health Research Program at the Ohio Agriculture Research and Development Center in Wooster. Below is a summary of media coverage from late April to the middle of May, 2009.
Students Learn Shelter Medicine at the Capital Area Humane Society
By Kristine McComis
In a perfect world, all animals would live in safe, loving homes and over-population issues would vanish. However, as the veterinary students at The Ohio State University College of Veterinary Medicine know all too well, this perfect balance does not exist. A Shelter Medicine rotation has traditionally made up part of the veterinary curriculum, and last year Ohio State improved the program by establishing a surgical partnership with the Capital Area Humane Society in Columbus, one of the most respected animal shelters in the state of Ohio.
BIOS Newsletter: June 2009
Dr. Maxey Wellman is the recipient of the 2009 Dean's Award in Creative Teaching; Department of Veterinary Biosciences Spring 2009 Graduates; Announcements; Wellness News: June is National Dairy Month...
BIOS Newsletter: May 2009
Dr. Patrick Green Distinguished Recipient, Dr. Irvin Chen honored, Anaplasmosis Organism Tricks Cell...
BIOS Newsletter: March 2009
Dr. Ian Davis receives career award for influenza research; Outreach and Engagement efforts; Wellness news; Grants and publications; Staff profile...
BIOS Newsletter: January 2009
Drs. Hernandez and Boris-Lawrie's Review Role of Proto-Oncogene, Dr. Boyaka Selected as National Program Chair, Announcements, Appointments...
BIOS Newsletter: February 2009
Distinguished Alumna Dr. Judith Gwathmey visits OSU; Drs. Rikihisa and Green elected as American Academy of Microbiology Fellows; staff profile Archna Hazelbaker...
BIOS Newsletter: April 2009
Dr. Nong Inpanbutr awarded Battelle Endowment; New NIH Training Grant; Drs. Wittum & Premanandan International Outreach...
Safe Summer program returns
The Safe Summer program offers solutions for college students who are leaving for the summer and may have a pet they cannot take with them. In past years, many pets were abandoned in empty apartments, or released to the street. Safe Summer was created by the Shelter Medicine Club of The Ohio State University College of Veterinary Medicine and is run by students and volunteers. The service will be available from May 26 through June 19, 2009 with the goal of finding a safe home for any pets left behind.


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LAS VEGAS, Nev. – NFC technology this year is likely to make its way into a greater variety of consumer products, including televisions, DVD players, digital cameras, even an automatic vacuum cleaner, if demonstrations at last week's International Consumer Electronics Show in Las Vegas are any indication.
Samsung Electronics has introduced its much-anticipated Galaxy S III, which, as expected, will support NFC for mobile payment, along with an enhanced version of Google's Android Beam peer-to-peer pairing-and-sharing feature.
Taiwan-based device maker Acer has announced its second NFC-enabled smartphone, the Liquid Glow, which will run Android 4.0, Ice Cream Sandwich.
Google has unveiled its Galaxy Nexus, its much-anticipated follow-up to the Nexus S, which the Web giant is touting as supporting NFC-based content-sharing functionality called "Android Beam." The feature is part of the latest version of Google's Android operating system, Ice Cream Sandwich.
NFC Times Exclusive Insight – A U.S. district court judge has ruled that T-Mobile USA infringed an NFC patent held by Israel-based On Track Innovations.
NFC Times Exclusive Insight – Another major New Zealand bank has announced plans to launch NFC payments with host-card emulation, snubbing a joint venture set up to launch SIM-based NFC on the island nation.
NFC Times Exclusive Insight – Windows 10 for phones, set to be released later this year, will support host card emulation, or HCE, based NFC payments, Microsoft revealed at a recent Windows event in China.
NFC Times Exclusive Insight – Germany-based Giesecke & Devrient confirmed it is providing the host-card emulation technology for Commonwealth Bank's commercial HCE launch this month of Tap & Pay from the bank's Android-based mobile-banking app.
Identiv CEO Jason Hart sounded optimistic tones about the company's NFC tag business, particularly in "Internet of Things" applications or tags for consumer goods, during a conference call last week to discuss Identiv's fourth quarter and full year 2014 earnings, but investors responded with less optimism.
NFC Times Exclusive Insight – France-based Gemalto, which is keen to take the spotlight off its SIM business, projects EMV cards to represent perhaps the largest expected source of revenue growth in the coming year.
NFC Times Exclusive Insight – UPDATED: Mobile point-of-sale device supplier Square has acquired payment processing component vendor Kili Technology, the same vendor that purchased NFC accessory vendor DeviceFidelity in November, but Square does not plan to keep DeviceFidelity, a source connected with Square told NFC Times.
NFC Times Exclusive – NFC Times has learned new details about how Samsung intends to make money from its planned payments service, Samsung Pay; as well as the technology architecture the OEM will use and the identity of two unannounced banks, along with a new category of issuer that is planning to participate.
NFC Times Exclusive – The public relations debacle Gemalto faced following revelations last month that U.S. and UK spy agencies had stolen keys from its SIM cards is not the only problem the France-based vendor has had to deal with regarding SIMs.
NFC Times Exclusive – MasterCard Worldwide has named James Anderson group executive for platforms, a key position inside the payment network, which is seeking to secure its role in the ecosystem as mobile payments start to gather steam, NFC Times has learned.
NFC Times Exclusive Insight – One of Australia's largest banks, Commonwealth Bank, is launching NFC payments from its mobile-banking app using host-card emulation, having earlier tried embedded secure elements, contactless stickers and iPhone attachments.
NFC Times Exclusive Insight – Google's recently announced API for NFC payments applications, Android Pay, is expected to support apps using host card emulation, or HCE, but also likely will support storage of keys on hardware.


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- New Hampshire
- Last Record: Jan 13, 2013
- Joined: Jan 05, 2013
- —
"You can't be serious," he says, barely perceptible over the bass-frenzied synth contorting the movement of air, light, and bodies through the room.
"Somebody will see. They will, and-"
"That's the point." I grin through the fibrillating thrash and pulse, inhaling his sweat as it resonates in the distant magnetic longing of our atoms, drunk and seeking the warm comfort of skin or oblivion.
"--and they'll call the fucking cops and we'll be, like, required to register as sex offenders. Or at least get a few months in prison for criminal intent. Jesus Christ, you're insane." His eyes are unfocused, and he puts a hand on the bar stool to steady that earnest and transparent gaze which, once adored, now conjures nothing but a tired disgust.
"Social deviance is still well within the confines of the law. Now shut up and hold this," handing him a red solo cup of punch and removing the placebo, encased in its plastic and foil tamper proof packaging.
"It's harmless. There's our victim. Catch her eye." A mani/pedi tart, brunette, oblivious, and bobbing her head like a metronome. The pill, white and nondescript in his hand, as he elbows his way through the thick, heated sea of flesh, conversing in some unspoken rhythm only the muscles remember with fluency. He breaks the pill in half and she senses with the remains of a dormant intuition that peripheral movement as he smiles, reluctantly, in her direction. A flash of white dropped in the blush pink depths of punch, the liquid parting to swallow it whole.
"Care for a drink?" he says, extending his arm with the cup like an offering, a sacrament...
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Jan 13, 2013
Jan 05, 2013
Peddled by fatalists and the crown jewel of soothsayers, this intangible and sublimely binary concept is, like a depthless wellspring from which we eternally withdraw, or notch, in...
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Jan 05, 2013


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Cancer Therapy Vol 5, page 77 Cancer Therapy Vol 5, 77-88, 2007 The role of chemotherapy in the treatment of advanced non-small cell lung cancer elderly patients Review Article Antonio Rossi, Paolo Maione, Giuseppe Colantuoni, Carmine Ferrara, Alba De Vita, Ciro Guerriero, Dario Nicolella, Filomena del Gaizo, Cesare Gridelli* Division of Medical Oncology, "S.G. Moscati" Hospital, Avellino – Italy __________________________________________________________________________________ *Correspondence: Cesare Gridelli, M.D., Division of Medical Oncology, "S.G. Moscati" Hospital, Città Ospedaliera, Contrada Amoretta, 83100 Avellino, Italy; Tel: + 39 0825 203573; Fax: + 39 0825 203556; e-mail: email@example.com Key words: NSCLC, elderly patients, chemotherapy Abbreviations: Eastern Cooperative Oncology Group, (ECOG); Elderly Lung cancer Vinorelbine Italian Study, (ELVIS); comprehensive geriatric assessment, (CGA); median survival time, (MST); Multicenter Italian Lung cancer in the Elderly Study, (MILES); non-small-cell lung cancer, (NSCLC); overall response rates, (ORR); performance status, (PS); progression-free survival, (PFS); quality of life, (QoL); small-cell lung cancer, (SCLC); Southwest Oncology Group, (SWOG); time to progression, (TTP) Received: 27 December 2006; Revised: 19 January 2007 Accepted: 30 January 2007; electronically published: March 2007 Summary More than 50% of non-small-cell lung cancer (NSCLC) patients are diagnosed over the age of 65 and approximately one-third of all patients are over the age of 70. Elderly patients tolerate chemotherapy poorly compared to their younger counterpart because of the progressive reduction of organ function and comorbidities related to age. This is why these patients are often not considered eligible for aggressive platinum-based chemotherapy, the standard of care for advanced NSCLC. With the current evidence, in clinical practice, single- agent chemotherapy with a third-generation drug should be the recommended option for non-selected elderly patients with advanced NSCLC. Subset analyses suggest that the efficacy of platinum-based combination chemotherapy is similar in fit older and younger patients, with an acceptable increase in toxicity for elderly patients. However, feasibility of platinum-based chemotherapy remains an open issue and has to be proven in prospective randomised trials. High priority should be also given to the evaluation of the role of new targeted therapies. Moreover, a comprehensive geriatric assessment for individualized treatment choice in NSCLC elderly patients is mandatory. The Authors review the currently-available evidences for the treatment of elderly patients affected by advanced NSCLC reporting their own experiences in the field. I. Introduction (Fentiman et al, 1990). Moreover, many of these patients More than 50% of lung cancers, the leading causes of have pre-existing co-morbid conditions, which, cancer-related deaths in Europe and in other Western independent of cancer-related symptoms, may adversely countries, are diagnosed in patients aged over 65 and affect organ function and impact on functional status about 30% in patients aged over 70 (Jemal et al, 2006). In (Yancik et al, 2001). Further, co-morbidities often require the United States (US), approximately 13% of the patients treatment with multiple drugs, which may interfere with have small-cell lung cancer (SCLC) and, consequently, chemotherapy or its toxicity profile. Moreover, the more than 85% have non-small cell lung cancer (NSCLC) disparity between apparent decreased cancer (Govindan et al, 2006). Clearly, lung cancer in elderly aggressiveness in an individual patient and the high rate of patients is an increasingly common problem which the cancer mortality in older age groups may be because the practitioner of oncology must face. survival data are confounded by special problems common Since most patients with NSCLC have advanced to geriatric populations (comorbidity, 'poly-pharmacy', disease at diagnosis, chemotherapy is the mainstay of physician or family bias regarding diagnosis and treatment management. Elderly patients often present with medical of elderly, age-associated life stresses). These factors may and physiological characteristics that make the selection of increase death rates and counteract any primary influence their optimal treatment more challenging. Unfortunately, that aging might have to reduce tumour aggressiveness as a result, these patients are at risk of being under-treated (Ershler and Long, 1997). 77 Rossi et al: The role of chemotherapy in the treatment of advanced non-small cell lung cancer elderly patients In current practice, the elderly, often excluded from In order to further individualize treatment choice in participation in clinical trials, receive untested or elderly patients, it is important to practice not only the inadequate treatment, based on a long-held but completely patient's basic medical history and the standard cancer undocumented notion that cancers in older people are less staging, but also a comprehensive geriatric assessment aggressive (Rossi and Gridelli 2006). Lung cancer is no (CGA). The CGA includes assessment of comorbidity, exception to this observation; on the contrary, data show socio-economic issues, nutritional status, poly-pharmacy, that it can be considered the paradigm of elderly under- functional dependence, emotional and cognitive representation in clinical research (Hutchins et al, 1999; conditions, an estimate of life expectancy and recognition Lewis et al, 2003; Yee et al, 2003). To confirm these data, of frailty. All these various facets of the patient's health a recent survey analyzing trials for cancer drug registration and environment may interfere with therapy. CGA has conducted over seven years (from 1995 to 2002), showed been demonstrated to add substantial information with a great disparity between percentages of elderly patients in respect to the functional assessment of elderly cancer the general population and in those on clinical trials for patients (Repetto et al, 2002) allowing important lung cancer: 67% versus 35% (Talarico et al, 2004). prognostic discrimination even among patients Under-representation was particularly notable for patients characterized by a good performance status (PS). The older than 75 years. This phenomenon can significantly CGA may be too lengthy for a busy clinical practice. affect the generalizability of trial results that depend Therefore, a number of screening instruments have been largely upon whether subjects enrolled in clinical trials are developed to select those older patients who may benefit fully representative of the entire spectrum of patients from a full CGA. Of these, the evaluation proposed by the suffering from that disease. Cardiovascular Health Study, that allows the classification We must consider that it is very difficult to establish of elderly patients into three groups (fit, pre-frail, frail) a maximum age for chemotherapy in the elderly. Within according to five items (unintentional weight loss, self- epidemiological literature the age of 65 is usually reported exhaustion, weakness, walking speed and level of considered as a cut-point to select elderly population. On physical activity) (Fried et al, 2001) has gained particular the contrary, in clinical trials, the age of 70 is frequently prominence, because it is well correlated with mortality used as lower limit for patient selection while a cut-off age and risk of functional dependence. This classification has of 75 years is less common. Obviously, indirect been proposed as a standard language for the classification comparison of trials including or not patients aged 65 to of older individuals. Another simple screening instrument 70 may be biased. In clinical practice biological instead of is the Vulnerable Elderly Survey 13 (VES-13), which chronological age should be considered. Unfortunately, to includes 13 simple questions, the answers of which are date, laboratory tests and geriatric evaluation are scored; patients whose total score is four or higher may inadequate to define ageing; therefore, at present, benefit from a full CGA (Saliba et al, 2001). Also patients' chronological age should be used as a frame of reference self-reported quality of life (QoL) evaluation can add for clinical trials. A cut-off of 70 years of age seems to be significant prognostic information. When the prognostic the most appropriate. In fact, 70 years of age may be role of the baseline QoL, as measured by the EORTC C30 considered as the lower boundary of senescence, because global QoL score, was evaluated in elderly patients the incidence of age-related changes starts to increase after diagnosed with NSCLC, QoL score was a strong and the age of 70 years (Balducci, 2000). independent prognostic factor for survival in patients The evidence regarding the tolerability and efficacy undergoing first-line treatment for their NSCLC (Maione of anticancer treatments for elderly patients affected by et al, 2005). These results confirm also in elderly patients NSCLC comes from two different types of publications: the strong prognostic role of self-assessed QoL in patients prospective clinical trials specifically designed for the with advanced lung cancer (Ganz et al, 1991) and show elderly and, retrospective analyses conducted on the that a simple, self-reported questionnaire may add useful subgroup of elderly patients enrolled onto clinical trials information to baseline evaluation of the patient. that did not have an upper age limit. For the latter type of This report is focused on the currently-available studies, it is easy to argue that when a clinical trial is evidences for the treatment of elderly patients affected by designed to test the efficacy of a treatment intended for advanced NSCLC and the Authors report their own younger patients, only a selected proportion of elderly experiences in this setting. patients will be considered for enrolment, and so the results may not necessarily extend to the general non- II. Single-agent chemotherapy selected elderly population (Perrone et al, 2002). In fact, a The introduction into clinical practice of new, active recent report demonstrated that elderly specific trials are and well-tolerated drugs has stimulated clinical research. needed to define optimal cancer therapy in this subset of The first randomized phase III trial in advanced NSCLC patients. This was a pooled analysis of elderly patients elderly patients was the Elderly Lung cancer Vinorelbine who participated in elderly-specific trials (age > 65 years) Italian Study (ELVIS). In this trial, 161 chemotherapy- or in age-unspecified studies (age > 18 years). The median naïve patients (! 70) were randomized to receive age of elderly patients was greater in elderly-specific trials vinorelbine (30 mg/m2 on days 1 and 8, every 3 weeks) or and the toxicity reported in elderly patients was lower in best supportive care (ELVIS Group 1999). A significant elderly-specific trials than that reported in age-unspecified survival advantage with a better QoL was observed for studies (Jatoi et al, 2005). It means that elderly-specific vinorelbine compared with the control group (median trials are providing quality care in the elderly. survival time [MST]: 27 versus 21 weeks, P = 0.04). 78 Cancer Therapy Vol 5, page 79 Patients treated in the vinorelbine arm scored better than III. Non-platinum-based controls on many QoL subscales. The ELVIS trial represents a landmark regarding the feasibility and the polichemotherapy palliative role of chemotherapy in elderly advanced In order to improve the results obtained with single- NSCLC patients. agent chemotherapy, some non-platinum-based Gemcitabine is one of the most widely used drugs for combinations have been developed. The most studied non- the treatment of NSCLC. Several phase II trials platinum-based regimen is gemcitabine plus vinorelbine. specifically designed for elderly patients with advanced Two phase III trials have compared gemcitabine plus NSCLC have confirmed the role of gemcitabine in this vinorelbine combination with a single-agent therapy setting. In patients older than 70 years, gemcitabine (Frasci et al, 2000; Gridelli et al, 2003). A small study of yielded overall response rates (ORR) of 18% to 38% and gemcitabine 1200 mg/m2 plus vinorelbine 30 mg/m2 MST of 6.8 to 9 months (Ricci et al, 2000; Altavilla et al, versus vinorelbine 30 mg/m2 alone (n = 120 patients) 2000; Martoni et al, 2001; Gridelli et al, 2001). closed early when an interim analysis showed that the Gemcitabine was generally well tolerated, with only two of combination conferred a significant survival advantage these studies showing any grade 3 to 4 hematologic over the single agent (MST: 29 versus 18 weeks, p < 0.01) toxicities. and a better ORR (Frasci et al, 2000). However, the 18- The taxanes (paclitaxel and docetaxel) have week survival for single-agent vinorelbine in this study is demonstrated both activity and tolerability in the treatment markedly lower than the 28- to 38-week survival times of advanced NSCLC. A recent review of two phase II trials reported in six large randomised trials, including three of paclitaxel 210 mg/m2 every 3 weeks compared outcome studies dedicated entirely to elderly patients (Rossi et al, according to age (< 70 versus ! 70 years). This analysis 2005; Kudoh et al, 2006). The Multicenter Italian Lung cancer in the Elderly Study (MILES) trial, enrolling 700 showed no differences in ORR or MST between the age patients with NSCLC, is the largest phase III study of the groups but the most frequent toxicity, neutropenia, tended elderly published to date (Gridelli et al, 2003). Patients to occur more frequently in the older patient group (89.3% were randomised to receive single-agent chemotherapy versus 73.9% in younger patients) (Nakamura et al, 2000). with vinorelbine 30 mg/m2 or gemcitabine 1200 mg/m2 or In an effort to reduce toxicity, weekly regimens of single- combination therapy with vinorelbine 25 mg/m2 plus agent paclitaxel have been investigated in three phase II gemcitabine 1000 mg/m2, all treatments recycled every 3 studies resulting in ORR and MST ranging from 3% to weeks. Combination treatment had no advantage in terms 23% and from 6.8 to 10.3 months, respectively, with of ORR, time to progression (TTP), MST or QoL over reasonable toxicity profiles (Fidias et al, 2001; Garbo et al, single-agent therapy. Moreover, although toxicity was 2001; West et al, 2001). Regarding docetaxel, in a phase II considered acceptable in all groups, it was higher with the trial, weekly doses of docetaxel were well tolerated combination than with the single agents. The authors (Hainsworth et al, 2000). A phase II randomized trial of concluded that single-agent therapy with vinorelbine or the two different schedules of administration of docetaxel gemcitabine is preferable to the combination for treatment (weekly or every 3 weeks) in advanced NSCLC elderly of advanced NSCLC in elderly patients. patients or patients with PS 2 confirmed comparable Table 1 summarises the randomized phase III trials activity and lower hematologic toxicity for the weekly performed in advanced NSCLC elderly patients. schedule (Lilenbaum et al, 2004). Recently, a randomized phase III trial reported that docetaxel (60 mg/m" day 1 every 3 weeks) provided IV. Platinum-based chemotherapy significantly longer progression-free survival (PFS) (5.5 Cisplatin administration is associated with significant months versus 3.1 months; p < 0.001), a significantly haematological and non-haematological toxicity higher ORR (22.7% versus 9.9%; p = 0.019) a more (nephrotoxicity, ototoxicity, neurotoxicity) and the favourable 1-year survival rate (58.6% versus 36.7%) and evaluation of the risk versus benefit ratio should be significantly better disease-related symptom improvement particularly rigorous in elderly patients. In this patient than vinorelbine (25 mg/m" days 1 and 8, every 3 weeks) population, reduction of creatinine clearance and cisplatin in elderly patients with advanced NSCLC (Kudoh et al, renal excretion is expected to increase the potential for 2006). These trial, enrolling 182 patients, fails to detect a toxicity, and the presence of comorbidities and significant difference in MST, the primary objective of the compromised PS may preclude cisplatin administration in study, despite a longer median survival in favour of a significant proportion of elderly patients (Oshita et al, docetaxel-treated patients than vinorelbine-treated patients 1995). (14.3 versus 9.9 months, respectively; p = 0.065). Major Compared to cisplatin, carboplatin causes lower rates toxicity was grade 3-4 neutropenia in both arms, 82.9% in of emesis, nephrotoxicity and neurotoxicity, and it docetaxel and 69.3% in vinorelbine group (p = 0.031). represents an appealing alternative for platinum-based This is the first prospective, randomized phase III trial in chemotherapy, although safety remains a problem which a single-agent treatment results superior, in several especially in terms of hematological toxicity, particularly outcomes but the primary end-point, to another one in the if it is administered in combination with other myelotoxic treatment of advanced NSCLC elderly patients. Therefore, agents. Platinum-based chemotherapy for elderly patients further larger phase III trials needed to confirm these with advanced NSCLC has been evaluated both in results. retrospective and prospective trials. 79 Rossi et al: The role of chemotherapy in the treatment of advanced non-small cell lung cancer elderly patients Table 1. Results from phase III trials of advanced non-small-cell lung cancer in elderly patients. Author Regimen Age (years) No.pts RR (%) MST (months) ELVIS trial, 1999 Vinorelbine 76 20 6.5 vs ! 70 Best Supportive Care 78 NA 4.8 Frasci, 2000 Vinorelbine 60 15 4.2 vs Vinorelbine + Gemcitabine ! 70 60 22 6.7 Gridelli, 2003 Vinorelbine or 233 18 8.3 Gemcitabine 233 16 6.5 vs ! 70 Vinorelbine + Gemcitabine 232 21 6.9 Kudoh, 2006 Vinorelbine 91 9.9 9.9 vs > 70 Docetaxel 88 22.7 14.3 ELVIS = Elderly Lung cancer Vinorelbine Italian Study; RR = response rate; MST = median survival time; NA = not applicable. A. Retrospective analyses of platinum- vinorelbine, and the SWOG 9308 trial that compared based chemotherapy cisplatin plus vinorelbine with cisplatin alone (Nguyen et The issue of cisplatin- and carboplatin-based therapy al, 1999). The results showed no statistically significant for elderly patients with advanced NSCLC has been influence of age on MST (8.6 versus 6.9 months for < 70 addressed in some retrospective analyses of large versus ! 70 year old patients; p = 0.06), TTP (4.2 versus randomised trials without an upper age limit in the 3.9 months; p = 0.62) or toxicity. Moreover, these trials inclusion criteria (Nguyen et al, 1999; Kelly et al, 2001; seem to support the higher tolerability of carboplatin Langer et al, 2002, 2003; Rocha Lima et al, 2002; Hensing versus cisplatin, at least at a dose of 100 mg/m2: 46% of et al, 2003; Belani and Fossella 2005; Belani et al, 2005; elderly patients who received cisplatin and vinorelbine Lilenbaum et al, 2005). discontinued chemotherapy due to unacceptable toxicity, A retrospective analysis of Eastern Cooperative and this proportion was significantly higher than the Oncology Group (ECOG) 5592 compared the effects of discontinuation rate for toxicity in younger patients. In first-line cisplatin plus either etoposide or paclitaxel in 86 contrast, only 16% of elderly patients treated with patients aged ! 70 years with those in 488 younger carboplatin and paclitaxel stopped treatment for toxicity patients (Langer et al, 2002). There were no significant reasons, without a significant age-related trend (Nguyen et differences between the younger and older patients in any al, 1999). A third retrospective study of a trial of two of the efficacy measures, with only minimal differences in different schedules of carboplatin plus paclitaxel toxicity between the age groups (the elderly had worse confirmed these findings (Hensing et al, 2003). leukopenia and neuropsychiatric disorders). An additional Other elderly subset analyses have also been reported analysis of the small subset of patients aged > 75 revealed recently (Lilenbaum et al, 2005; Belani and Fossella no differences in outcomes compared with patients aged 2005). The Cancer and Leukemia Group B (CALGB) 70–75, and there was only a borderline increase in compared carboplatin plus paclitaxel with paclitaxel alone leukopenia in the older age group (p = 0.06). and found no differences in MST between patients aged < Langer et al, also analysed data from ECOG 1594 in 70 and those aged > 70. A secondary analysis of the study which four treatment combinations (cisplatin/paclitaxel, showed that the survival advantage for the platinum-based cisplatin/docetaxel, cisplatin/gemcitabine and doublet was also seen in the subgroup of elderly patients carboplatin/paclitaxel) were evaluated as first-line (8 versus 5.8 months), although this difference was not chemotherapy for NSCLC (Langer et al, 2003). No statistically significant, due to the limited number of significant differences were reported for RR (24.5% elderly enrolled (Lilenbaum et al, 2005). First-line versus 22.1%) or MST (8.3 versus 8.2 months) for the 227 docetaxel plus either cisplatin or carboplatin was patients (20%) aged ! 70 compared with those aged < 70. compared with vinorelbine plus cisplatin in the TAX 326 Only a marginally significant (p = 0.04) increase in grade trial. A subset analysis of 401 patients aged ! 65 was 4 toxicities was reported in the elderly population. A conducted (Belani and Fossella 2005) and showed that similar retrospective analysis was undertaken for the docetaxel plus cisplatin provided substantial increases in Southwest Oncology Group (SWOG) 9509 trial, which survival (1 year: 52% versus 41%; 2 year: 24% versus compared carboplatin plus paclitaxel with cisplatin plus 17%) compared with vinorelbine plus cisplatin. Both docetaxel regimens were well tolerated in the elderly 80 Cancer Therapy Vol 5, page 81 subgroup, although the lowest incidence of toxicity Table 2 summarizes retrospective data analyses of occurred in the docetaxel plus carboplatin arm. elderly patients enrolled in phase III trials with platinum- Belani et al, reported retrospective analyses related to based chemotherapy. elderly patients randomized to receive carboplatin plus weekly paclitaxel versus carboplatin plus standard B. Prospective trials with platinum-based paclitaxel. For the elderly subgroup, the efficacy of the chemotherapy weekly regimen appeared to be higher in terms of RR, Prospective clinical trials of platinum-based TTP and MST with reduction in neuropathy as compared chemotherapy with inclusion criteria limited to the elderly to the standard regimen of paclitaxel and carboplatin population are needed. Interest in reproducing cisplatin (Belani et al, 2005). efficacy in elderly patients led to several prospective phase Overall, these analyses show a similar outcome of II trials testing the combination of third-generation platinum-based therapy for elderly patients compared to cytotoxic agents with cisplatin in modified schedules or their younger counterparts, in terms of RR and MST, with attenuated doses to obtain an active and well-tolerated a small but significant increase in toxicity in the elderly treatment. These employed schemas are not the and no significant adverse effect on QoL. conventional ones (75-100 mg/m" on day 1, every 3 However, it must be noted that the aforementioned weeks) in fact, weekly regimens (Lippe et al, 2000; analyses suffer from selection bias. In fact, the percentage Mattioli et al, 2002; Berardi et al, 2003; Ohe et al, 2004), of elderly patients enrolled in these studies did not exceed fractionated doses (Buffoni et al, 2006), low doses (Feliu 20% of the actual study population. So, elderly patients et al, 2003) and 4 weeks recycled schedules (Perreira et al, enrolled in these sort of trials are not representative of the 2004), were used in order to improve chemotherapy whole elderly population but rather of a small subgroup tolerability. Four main phase II trials tested the thought by investigators to be eligible for aggressive combination of cisplatin and gemcitabine reporting a ORR treatments (Perrone et al, 2002). ranging between 32-44% with a MST of 9-10 months. Table 2. Retrospective data analyses of elderly patients enrolled in phase III trials with cisplatin- or carboplatin-based chemotherapy Author Treatment Age No.pts RR (%) MST P (months) Nguyen, 1999 CDDP+GEM > 70 53 15 7.7 n.s. < 70 207 29 9.4 Kelly, 2001 CBDCA+TAX > 70 117 n.r. 6.9 0.06 CDDP+VNR < 70 491 n.r. 8.6 Langer, 2002 CDDP+VP-16 > 70 86 23.3 8.5 n.s. CDDP+TAX < 70 488 21.5 9.1 Rocha Lima, 2002 CDDP+VBL > 70 31 16 5.7 n.s. < 70 222 31 8.0 Langer, 2003 CDDP+TAX CDDP+TXT > 70 227 25 8.3 n.s. CDDP+GEM < 70 912 22 8.2 CBDCA+TAX Hensing, 2003 CBDCA+TAX > 70 67 27 7.1 n.s. < 70 163 20 7.8 CDDP+TXT > 65 149 n.r. 12.6 n.s. all ages 408 32 11.3 Belani, 2005 CDDP+VNR > 65 134 n.r. 9.9 n.s. all ages 404 25 10.1 CBDCA+TXT > 65 118 n.r. 9.0 n.s. all ages 406 24 9.4 CBDCA+TAXw > 70 70 25.7 9.2 n.r. Belani, 2005 < 70 147 28.6 9.6 CBDCA+TAX > 70 63 19 7.7 n.r. < 70 151 19.2 11.4 Lilenbaum, 2005 CBDCA+TAX > 70 77 36 8.0 n.s. < 70 207 30 8.5 CDDP = cisplatin; CBDCA = carboplatin; TAX = paclitaxel; TXT = docetaxel; VNR = vinorelbine, GEM = gemcitabine; VBL = vinblastine; VP-16 = etoposide; RR = response rate; MST = median survival time; S = survival; w = weekly; n.r. = not reported; n.s. = not significant. 81 Rossi et al: The role of chemotherapy in the treatment of advanced non-small cell lung cancer elderly patients The treatment was well tolerated (Lippe et al, 2002; or more achieved similar benefit from this combination in Berardi et al, 2003; Feliu et al, 2003; Moscetti et al, 2005). terms of RR and MST with equally good tolerability of The cisplatin plus vinorelbine schedule has been tested in younger ones (Masters et al, 2005). three phase II trials reporting a ORR of 33-50% with a Variable results have been observed with attenuated MST of 7.4-11 months. This combination was safe, too doses or modified weekly schedules of carboplatin plus (Mattioli et al, 2002; Pereira et al, 2004; Buffoni et al, paclitaxel; RRs have ranged from 14% to 60.9% and 2006). Ohe et al, treated 33 patients aged > 75 years with MSTs from 7.1 to 13.6 months (Jatoi et al, 2003; Choi et weekly cisplatin plus docetaxel reporting a ORR of 52% al, 2003; Okamoto et al, 2003; Marsland et al, 2005; Inoue and a MST of 15.8 months with a modest toxicity (Ohe et et al, 2006; Pujol et al, 2006). al, 2004). Table 4 summarises the results of phase II trials with The results of phase II trials employing third third-generation carboplatin-based chemotherapy in generation cisplatin-based chemotherapy are reported in advanced NSCLC elderly patients employing attenuated Table 3. doses or weekly administration of carboplatin. Among the new generation carboplatin-based regimens, two phase II studies were performed adding V. Targeted therapies carboplatin to vinorelbine, but reported activity (14% and Gefitinib (ZD1839, Iressa) and erlotinib (OSI774, 27% RR) does not suggest any clinical improvement Tarceva), two orally available selective and reversible compared to single agent chemotherapy also in inhibitors of epidermal growth factor receptor (EGFR) consideration of a significant rate and degree of tyrosine kinase, have demonstrated activity as single-agent mielotoxicity (Colleoni et al, 1996; Santomaggio et al, therapy in heavily pretreated patients with NSCLC 1996). In contrast, the combination of low-dose (Gridelli et al, 2004). carboplatin (AUC 4) and gemcitabine produced a RR of Subset analysis of several studies that have included 37.5% and a MST of 9.0 months, with a favourable patients aged ! 70 years suggests that gefitinib is active toxicity profile (Maestu et al, 2003). Recently, the results and generally well tolerated in this population (Gridelli et of a subset analysis of carboplatin plus gemcitabine from a al, 2004). The combination of gefitinib with either randomized phase II study were reported. Patients aged 70 Table 3. Phase II trials of cisplatin-based chemotherapy with third-generation agents and modified schedules or attenuated doses of cisplatin Author Regimen CDDP dose Age (years) No. Pts RR (%) MST (months) Mattioli, 2002* CDDP + VNR 25 mg/m2, weekly > 65 36 36 11 Pereira, 2004 CDDP + VNR 60-90 mg/m" > 70 44 50 7.5 Buffoni, 2006 CDDP + VNR 30 mg/m", day 1 and 8 > 70 30 33 7.4 Lippe, 2002 CDDP + GEM 35 mg/m2, weekly ! 65 29 48 10 Berardi, 2003 CDDP + GEM 35 mg/m2, weekly ! 70 48 31.8 9 Feliu, 2003 CDDP + GEM 50 mg/m2 ! 70 46 35 10.2 Moscetti, 2005 CDDP + GEM 75 mg/m", day 2 > 65 46 45.6 15 Ohe, 2004 CDDP + TXT 25 mg/m2, weekly ! 75 33 52 15.8 *including 3 unfit patients; CDDP = cisplatin; VNR = vinorelbine; GEM = gemcitabine; TXT = docetaxel; RR = response rate; MST = median survival time; S = survival Table 4. Phase II trials of modified administration of carboplatin-based chemotherapy with third-generation agents Author Regimen Age (years) No. RR (%) MST (months) Colleoni, 1996 Carboplatin + vinorelbine ! 70 22 14 n.r. Santomaggio, 1996 Carboplatin + vinorelbine ! 60 44 27 6.5 Maestu, 2003 Carboplatin + gemcitabine ! 65 88 37.5 9.0 Masters, 2005° Carboplatin + gemcitabine > 70 32 43.3 10.2 Jatoi, 2003 Carboplatin + paclitaxel > 65 49 14 1-year S 31% Choi, 2003* Carboplatin + paclitaxel ! 65 35 40 8.6 Okamoto, 2005 Carboplatin + paclitaxel ! 70 25 28 12.3 Carboplatin ! paclitaxel 61 22.4 8.2 Marsland, 2005* ! 70 Carboplatin + paclitaxel 60 60.9 9.2 Inoue, 2006 Carboplatin + paclitaxel ! 70 42 45 14 Pujol, 2006 Carboplatin + paclitaxel > 70 51 43 13.6 °Retrospective analysis from a phase II study; *Including unfit patients; RR = response rate; MST = median survival time; n.r. = not reported; S = survival 82 Cancer Therapy Vol 5, page 83 vinorelbine or gemcitabine was investigated in a VI. Octogenarians prospective study of 60 patients aged ! 70 years with In general, little data exist regarding the outcome of advanced NSCLC. Gefitinib combined with gemcitabine chemotherapy in NSCLC patients aged 80 or more, a showed low activity, but was generally well tolerated. In rapidly expanding, potentially vulnerable population contrast, toxicity was unacceptable in the vinorelbine arm cohort. In an age-specific subanalysis of trial ECOG 1594, in which 18 of 25 patients (72%) had grade 3/4 investigators observed only 9 patients more than 80 years neutropenia, and there were 3 treatment-related deaths of age (less than 1% of all enrolees). It is notable that only with no ORR reported (Scagliotti et al, 2004). Very 1 of these 9 patients was able to complete four cycles of recently, erlotinib has been tested prospectively in a phase chemotherapy. Efficacy in this group was very poor: 0% II study in patients aged more than 70 years with ORR; PFS of 2.2 months, and MST of only 4.2 months. previously untreated advanced NSCLC. Preliminary These patients fared worse than patients aged 70-79 when results on 80 patients, suggest that erlotinib is well treated with platinum-based combinations with time to tolerated with encouraging activity (ORR of 10.9%) as progression and survival roughly half that observed in the first-line treatment of advanced NSCLC of elderly much larger cohort of patients 70-79 years of age (Langer patients. Adverse events were generally mild, although all et al, 2003). responding patients developed a rash (which in 2 cases A combined analysis of two separate trials performed was severe) (Jackman et al, 2005). in elderly patients provides additional information Recently, we concluded the accrual in a randomized (Hesketh et al, 2005). One study compared weekly phase II study, named CALC-1 (Cetuximab in Advanced docetaxel to every 3-week docetaxel, and enrolled 26 Lung Cancer), in which cetuximab (IMC-C225), a human- patients aged 80 or older. The second trial, tested mouse chimeric anti-EGFR monoclonal antibody, is sequential vinorelbine-docetaxel and included 23 patients administered in combination with gemcitabine or over age 80. Tolerance to treatment was similar between gemcitabine followed by cetuximab in advanced NSCLC patients aged 70-79 and those over 80 years. For patients patients unsuitable for combination chemotherapy. with performance status 0-1, median survival was actually The humanized monoclonal antibody bevacizumab, shorter in the octogenarian group compared to patients directed against vascular endothelial growth factor aged 70-79 (7 versus 11 months). For PS 2 patients, (VEGF), is the first and, currently, the only pure anti- survival was equally poor in both groups (4 versus 5 angiogenic agent licensed for use in combination with months). Clearly, more studies in this age group need to be fluorouracil-based chemotherapy for first-line treatment of conducted. patients with metastatic colorectal cancer in the US and Europe (Gridelli et al, 2006). The clinical development of bevacizumab combined with chemotherapy in the VII. Second-line chemotherapy treatment of advanced NSCLC has produced exciting Very recently, evidences regarding the feasibility of a results (Johnson et al, 2004; Sandler et al, 2006). These second-line chemotherapy in advanced NSCLC elderly studies represent the first evidence of superior efficacy of patients are emerging. A retrospective analysis of a targeted therapy combined with chemotherapy over randomized phase III trial of pemetrexed versus docetaxel chemotherapy alone in the treatment of NSCLC. Despite in the second-line treatment of advanced NSCLC showed squamous histology was excluded, because of risk of that elderly benefit of treatment as their younger grade 5 hemoptysis reported in the phase II randomized counterparts. study (Johnson et al, 2004), in the following phase III trial, The reported results for elderly patients are as there were 15 treatment-related deaths in bevacizumab follows: 47 patients enrolled in the pemetrexed arm and 39 group, including 5 from pulmonary haemorrhage (Sandler in the docetaxel group; TTP was 4.6 and 2.9 months, MST et al, 2006). No data about bevacizumab and elderly was 9.5 and 7.7 months, 12-months survival was 20.4% patients have been reported, but the toxicity profile of and 23.1%, 24-months survival was 6.1% and 10.6%, bevacizumab, does not appear particularly suitable to the respectively. A smaller number of patients, 40 in the elderly population, often characterised by cardiovascular pemetrexed group and 36 in the docetaxel arm, were comorbidities. In fact, a recent analysis from 1,745 evaluable for ORR which was 5% and 5.6% with a stable patients included in 5 different clinical trials, with disease of 60% and 41.7%, respectively. Overall, 40 different tumours, showed that 7.1% of patients older than patients in the pemetrexed group and 37 in the docetaxel 65 years and treated with bevacizumab suffered arm were evaluable for grade 3-4 toxicity reported thromboembolic complications, and that it went up to neutropenia in 12.5% and 29.7%, neutropenia febrile in 17.9% in those with a previous history of atherosclerosis 2.5% and 18.9%, anemia in 0% and 2.7%, muscle (Skillings et al, 2005). Moreover, bevacizumab is to be weakness in 5% and 0%, respectively (Weiss et al, 2006). administered intravenously and in combination with The authors concluded that for elderly patients with chemotherapy, thus not being associated with the advanced NSCLC and good PS, second-line cytotoxic advantages of oral single agent targeted therapies. In fact therapy is appropriate, with pemetrexed producing a more oral adiministration and the possibility of some targeted favorable toxicity profile compared to docetaxel. These agents to be administered without chemotherapy are results may appear very attractive, but we strongly suggest factors encouraging their use in elderly patients. to be careful in overemphasizing them, as they derived from a retrospective analysis which could be influenced by selection bias like that reported in the first-line setting. 83 Rossi et al: The role of chemotherapy in the treatment of advanced non-small cell lung cancer elderly patients In addition, a phase II trial reported good activity and of age. This group is a particularly attractive target for toxicity profile for a modified schedule of docetaxel (37.5 studies using molecular targeted and other potentially less mg/m2 on days 1 and 8 every 3 weeks) (Tibaldi et al, toxic oral single agents. 2006). While we are still working hard to define the best first-line treatment to be generalized for this growing VIII. Conclusions population, we are going into another minefield, such as NSCLC remains a major problem in the US, western second-line therapy. It may be very dangerous without a civilization, and developing countries. Unfortunately, correct and pragmatic strategy. In our opinion, only approximately 90% of all NSCLC patients will eventually second-line prospective studies, specifically addressed to die from their disease. SEER data in the U.S. suggest that elderly patients with advanced NSCLC, are welcome. 69 is the median age at diagnosis (Havlik et al, 1994). Moreover, in order to better define elderly patients With the aging of the population one may expect that the enrolled in clinical trials, every patient should receive a prevalence of lung cancer among the elderly will increase. complete functional assessment at baseline allowing a The use of chemotherapy in the elderly NSCLC clearer interpretation of trial results. population is complicated by a number of age-related issues. The reduced organ function and higher prevalence of comorbid disorders associated with the increasing of References age affect treatment decisions. This, together with the lack Altavilla G, Adamo V, Buemi B, Marabello G, Maisano R, Lupo G, Bene A, Bellocco G (2000) Gemcitabine as single agent of a clear definition of elderly, contributes to low numbers in the treatment of elderly patients with advanced non small of elderly participants being included in clinical trials. The cell lung cancer. Anticancer Res 20, 3675-3678. place of platinum-based treatment for elderly patients with Balducci L (2000) Geriatric oncology: challenges for the new NSCLC has traditionally been seen as questionable century. Eur J Cancer 36, 1741-1754. because of the perceived higher risk of toxicity. However, Belani CP, Fossella F (2005) Elderly subgroup analysis of a several retrospective subset analyses of platinum-based randomized phase III study of docetaxel plus platinum chemotherapy trials have demonstrated no or minimal combinations versus vinorelbine plus cisplatin for first-line differences between elderly patients who met the stringent treatment of advanced nonsmall cell lung carcinoma (TAX eligibility criteria of the clinical trials and younger patients 326). Cancer 104, 2766-2774. Belani C, Ramalingam S, Perry MC, LaRocca R, Rinaldi D, treated with platinum-based therapies. The results of Gable P, Tester W (2005) Phase III randomized trial subset analyses, however, should be interpreted with care comparing weekly vs. standard schedules of paclitaxel (P) due to the potential risk of selection bias. plus carboplatin (C) for advanced non-small cell lung cancer A new generation of clinical trials specifically (NSCLC): Analyses of elderly patients. Lung Cancer 49 designed for the elderly population are needed and should (suppl 2), S32 (abstr O-088). include the development and validation of new measures Berardi R, Porfiri E, Scartozzi M, Lippe P, Silva RR, Nacciarriti and tools to define 'biological' versus 'chronological' age. D, Menichetti ET, Tummarelo D, Carle F, Piga A, Cellerino Moreover, several treatment options should be evaluated R (2003) Elderly patients with advanced non-small cell lung such as non-platinum-based combination chemotherapy; cancer. A phase II study with weekly cisplatin and gemcitabine. Oncology 65, 198-203. platinum-based combination chemotherapy; new biologic Buffoni L, Dongiovanni D, Barone C, Fissore C, Ottaviani D, agents (Rossi et al, 2005). Dongiovanni V, Grillo R, Salvadori A, Birocco N, Schena With the evidence currently available from large M, Bertetto O (2006) Fractionated dose of cisplatin (CDDP) randomised trials, single-agent chemotherapy with a third- and vinorelbine (VNB) chemotherapy for elderly patients generation agent, can be considered a recommended with advanced non-small cell lung cancer: Phase II trial. option for elderly advanced NSCLC patients (Pfister et al, Lung Cancer 54, 353-357. 2004; Gridelli et al, 2005). However, which single-agent? Choi IS, Kim BS, Park SR, Lee SY, Kim DY, Kim JH, Lee SH, Several factors should be considered by the clinician when Kim TY, Heo DS, Bang YJ, Kim NK (2003) Efficacy of choosing the drug to be administered. This choice should modified regimen with attenuated doses of paclitaxel plus carboplatin combination chemotherapy in elderly and/or take into account the expected toxicity profile of the agent, weak patients with advanced non-small cell lung cancer. pharmacokinetics, organ function and co-morbidities. Lung Cancer 39, 99-101. Platinum-based chemotherapy may represent a valid Colleoni M, Vicario G, Pancheri F, Sgarbossa G, Nelli P, option for fit elderly patients with adequate organ Manente P (1996) Weekly carboplatin and vinorelbine in function. Obviously, a proper selection of these patients is elderly patients with non-small-cell lung cancer (NSCLC). mandatory and further experimental evidence on this topic Proc 6th International Congress on Anti-Cancer appears essential. Randomized phase III trials with Treatment. Paris, France p. 194 (abstract 562). adequate power to address the main questions regarding Elderly Lung Cancer Vinorelbine Italian Study Group (1999) the efficacy and tolerability of platinum-based Effects of vinorelbine on quality of life and survival of elderly patients with advanced non-small-cell lung cancer. J chemotherapy in advanced NSCLC elderly patients are Natl Cancer Inst 91, 66-72. needed, especially in selected elderly good PS patients Ershler WB, Long DL (1997) Aging and cancer: issues of basic (Rossi et al, 2005). and clinical science. J Natl Cancer Inst 89, 1489-1497. The lack of data on octogenarians remains Feliu J, Martin G, Madronal C, Rodriguez-Jaraiz A, Castro J, troublesome. Based on retrospective analyses, clinicians Rodriguez A, Checa T, Bolano M, Casado E, Gonzales- should exercise caution when applying the existing data Baron M (2003) Combination of low-dose cisplatin and for patients aged 70 to 79 years to the those over 80 years gemcitabine for treatment of elderly patients with advanced 84 Cancer Therapy Vol 5, page 85 non-small cell lung cancer. Cancer Chemother Pharmacol Institute SEER. Collaborative study on comorbidity and early 52,247-252. diagnosis of cancer in the elderly. Cancer 74 (suppl 7), Fidias P, Supko JG, Martins R, Boral A, Carey R, Grosbard M, 2101-2106. Shapiro G, Ostler P, Lucca J, Johnson BE, Skarin A, Lynch Hensing TA, Peterman AH, Schell MJ, Lee JH, Socinski MA TS (2001) A phase II study of weekly paclitaxel in elderly (2003) The impact of age on toxicity, response rate, quality patients with advanced non-small cell lung cancer. Clin of life, survival in patients with advanced, stage IIIB or IV Cancer Res 7, 3942-3949. nonsmall cell lung carcinoma treated with carboplatin and Frasci G, Lorusso V, Panza N, Comella P, Nicolella G, Bianco paclitaxel. Cancer 98, 779-88. A, De Cataldis G, Iannelli A, Bilancia D, Belli M, Massidda Hesketh PJ, Lilenbaum R, Chansky K, Dowlati A, Graham P, B, Piantedosi F, Comella G, De Lena M (2000) Gemcitabine Crowley J, Gandara DR (2005) Chemotherapy in patients ! plus vinorelbine versus vinorelbine alone in elderly patients 80 with advanced non-small cell lung cancer: combined with advanced non-small cell lung cancer. J Clin Oncol 18, results from SWOG 0027 and LUN 6. J Clin Oncol 23, 657s 2529-2536. (abstr 7147). Fried LP, Tangen CM, Walston J, Newman AB, Hirsch C, Hutchins LF, Unger JM, Crowley JJ, Coltman CA Jr, Albain KS Gottdiener J, Seeman T, Tracy R, Kop WJ, Burke G, (1999) Underrepresentation of patients 65 years of age or McBurnie MA (2001) Frailty in older adults: evidence for a older in cancer-treatment trials. N Engl J Med 341, 2061- phenotype. J Gerontol A Biol Sci Med Sci 56, M146-M156. 2067. Ganz PA, Lee JJ, Siau J (1991) Quality of life assessment. An Inoue A, Usui K, Ishimoto O, Matsubara N, Tanaka M, Kanbe independent prognostic variable for survival in lung cancer. M, Gomi K, Koinumaru S, Saijo Y, Nukiwa T (2006) A Cancer 67, 3131-3135. phase II study of weekly paclitaxel combined with Garbo L, Marsland T, Garfield D, Khan M, Asmar L (2001) A carboplatin for elderly patients with advanced non-small cell phase II study of weekly paclitaxel (Taxol) in stage IIIB, IV, lung cancer. 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Outdoor Living
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Comment: OpenWRT (Score 1) 238
Just as a heads up, I measured 18Mbps (that is 1.8MB/s) with my OpenWRT TP-link WDR4300 (with AR9344 @ 560MHz) . I don't think off-the-shelf routers have any openVPN support, so no HW encryption engines.
If you need higher speeds, forget off-the-self routers (at least for the VPN end-points).


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Thank you for making the dog park awesome :-) I love having a place where the pups can run free for
Thank you for making the dog park awesome :-) I love having a place where the pups can run free for a bit!
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Thank you for making the dog park awesome :-) I love having a place where the pups can run free for a bit!
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Grand Estates of Prosper offers luxurious 1, 2 and 3 bedroom apartments homes for rent with lake views and scenic jogging trails. Convenient location to HWY 380, HWY 75, Dallas Tollway, HWY 121, HWY 5, Preston Road and more! Our apartment community offers various amenities to fit your needs. Grand Estates of Prosper has resort-style swimming pool, scenic views, internet cafe w/ WiFi, and much more! Look to make Grand Estates of Prosper your next apartment home!
From the Dallas North Tollway, exit Hwy 380 and go right. Turn left on Coit and we're on the left.From US-75 exit Hwy. 380 and go west (left) on Hwy. 380 approx. 9 miles. Turn right on Coit and we're on the left.
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