Randomised, phase III trial of epoetin-β to treat chemotherapy-induced anaemia according to the EU regulation. Combined radiotherapy and chemotherapy with dibromodulcitol and CCNU in the postoperative treatment of malignant gliomas. Preoperative chemoradiotherapy versus preoperative radiotherapy in rectal cancer patients: assessment of acute toxicity and treatment compliance. Report of the 22921 randomised trial conducted by the EORTC Radiotherapy Group. Effects of counseling for late stage cancer patients. Feasibility of non-cisplatin-based induction chemotherapy and concurrent chemoradiotherapy in advanced head and neck cancer. A three-arm phase III randomised trial assessing, in patients with extensive-disease small-cell lung cancer, accelerated chemotherapy with support of haematological growth factor or oral antibiotics. Initial versus delayed accelerated hyperfractionated radiation therapy and concurrent chemotherapy in limited small-cell lung cancer: a randomized study. Effects of group CBT on the survival time of patients with metastatic breast cancer. Randomised comparison of combination chemotherapy plus supportive care with supportive care alone in patients with metastatic colorectal cancer. General condition of asymptomatic patients with advanced colorectal cancer receiving palliative chemotherapy. A longitudinal study. An intergroup phase III comparison of standard radiation therapy and two schedules of concurrent chemoradiotherapy in patients with unresectable squamous cell head and neck cancer. Improving the quality of life during chemotherapy for advanced breast cancer. A comparison of intermittent and continuous treatment strategies. Modified therapy with 5-fluorouracil, doxorubicin, and methotrexate in advanced gastric cancer. Adjuvant therapy in large bowel adenocarcinoma: long-term results of a Southwest Oncology Group Study. Role of elective brain irradiation during combined chemoradiotherapy for limited disease non-small cell lung cancer. Effects of prophylactic chemotherapy for persistent trophoblastic disease in patients with complete hydatidiform mole. Quality of life and survival in patients with advanced non-small cell lung cancer receiving supportive care plus chemotherapy with carboplatin and etoposide or supportive care only. A multicentre randomised phase III trial. Joint Lung Cancer Study Group. Phase III study of combined chemohormonal therapy in metastatic prostate cancer (ECOG 3882): an Eastern Cooperative Oncology Group study. Randomized comparison between chemotherapy plus best supportive care with best supportive care in advanced gastric cancer. Randomized trial of 3 different regimens of combination chemotherapy in patients receiving simultaneously a hormonal treatment for advanced breast cancer. Simultaneous radiochemotherapy versus radiotherapy alone in advanced head and neck cancer: a randomized multicenter study. Improving informed consent to chemotherapy: a randomized controlled trial of written information versus an interactive multimedia CD-ROM. Dietary counseling improves patient outcomes: a prospective, randomized, controlled trial in colorectal cancer patients undergoing radiotherapy. Supportive-expressive group therapy for women with metastatic breast cancer: survival and psychosocial outcome from a randomized controlled trial. Effect of a cognitive behavioral intervention on reducing symptom severity during chemotherapy. Sequential adjuvant chemotherapy and radiotherapy in endometrial cancer--results from two randomised studies. Chemotherapy can prolong survival in patients with advanced non-small-cell lung cancer--report of a Canadian multicenter randomized trial.
Erythropoietin-stimulating agents (ESAs) effectively decrease the transfusion requirements of patients with chemotherapy-induced anaemia (CIA). Recent studies indicate that ESAs increase mortality and accelerate tumour progression. The studies also identify a 1.6-fold increased risk of venous thromboembolism. The ESA labelling was thus revised in Europe and the United States in 2008. This is the first randomised, phase III trial evaluating the efficacy and safety of epoetin-β (EPO), an ESA, dosed in accordance with the revised labelling, which specifies that ESAs should be administered to CIA patients with a haemoglobin level of ≤ 10 g dl⁻¹ and that a sustained haemoglobin level of > 12 g dl⁻¹ should be avoided.
                A total of 186 CIA patients (8.0 g dl⁻¹ ≤ haemoglobin ≤ 10.0 g dl⁻¹) with lung or gynaecological cancer were randomised to receive EPO 36,000 IU or placebo weekly for 12 weeks.Results:The proportion of patients receiving transfusions or with haemoglobin < 8.0 g dl⁻¹ between week 5 and the end of the treatment period as the primary end point was significantly lower in the EPO group (n=89) than in the placebo group (n=92; 10.0% vs 56.4%, P < 0.001). The proportion receiving transfusions was significantly lower in the EPO group (4.5% vs 19.6%, P=0.002). Changes in quality of life were not different. No significant differences in adverse events - for example, the incidence of thromboembolic events was 1.1% for each group - or the 1-year overall survival were observed between groups.
                Weekly EPO administered according to the revised labelling approved by the European Medicines Agency is effective and well tolerated for CIA treatment. Further investigations are needed on the effect of ESAs on mortality. Within 4 weeks after definitive surgery, 91 patients with supratentorial glioblastomas and malignant astrocytomas were randomized to one of three treatment arms: Group 1 received radiotherapy alone; Group 2 received dibromodulcitol (DBD) during radiotherapy, and treatment was then continued with DBD; and Group 3 received DBD during radiotherapy, followed by combination chemotherapy of CCNU and DBD. No severe myelotoxicity occurred, but combined treatment with CCNU and DBD occasionally caused a transient myelosuppression. Statistical analysis of 84 evaluable patients showed a significantly longer survival period in those who received chemotherapy during and after irradiation. Median survival times in the three groups were 40, 57, and 60 weeks, respectively; the corresponding p value for Groups 2 and 3 was 0.025 and 0.0015. The ratio of patients surviving over 18 and 24 months was highest in Group 3. This study suggests that the administration of DBD during irradiation might have been the main factor in improving survival times. The European Organisation for Research and Treatment of Cancer (EORTC) 22921 four-arm randomised trial questioned the value of preoperative chemoradiation (XRT-CT) versus preoperative radiation (XRT) and the value of additional postoperative chemotherapy (CT) versus none in T3-T4 M0 resectable rectal cancer patients. We report on the preoperative toxicity, treatment compliance and early deaths (all deaths up to 30 days after surgery) of the two treatment modalities in patients who were entered into trial before January 2001. In the XRT Group (group A), patients received 45 Gy, 25 fractions over 5 weeks. In the XRT-CT Group (group B), two 5-day courses of CT were added to the first and fifth weeks of XRT. For each CT course: 5-fluorouracil (5-FU) 350 mg/m2/day and Leucovorin (LV) 20 mg/m2/day were given. 398 and 400 patients started treatment in groups A and B, respectively. Grade 2+acute diarrhoea occurred in 17.3 and 34.3% of patients in groups A and B, respectively (P<0.005). The other side-effects remained unchanged or were only marginally increased. The compliance with RT was 98.5 and 95.5% in groups A and B, respectively. In group B, 78.7 and 71.1% of the patients received 95-105% of the planned CT doses at the first and second courses, respectively. 6 patients died preoperatively, 2 from toxicity in group B. 8 patients (1%) died within the 30 days after surgery in both groups. At the doses recommended in the protocol, the addition of 5-FU-LV to preoperative XRT slightly increased the amount of acute toxicity. However, the compliance with the radiation protocol or the feasibility of surgery did not decrease. Much has been written about working with the dying. Few, if any, controlled studies have examined the application of principles set forth. The authors evaluate the effectiveness of working with dying cancer patients by assessing changes in quality of life, physical functioning, and survival. One-hundred twenty men with end-stage cancer were randomly assigned to experimental or control groups; the 62 experimental group patients were seen regularly by a counselor. Patients were assessed before random assignment and at one, three, six, nine, and 12 months on quality of live and functional status. Experimental group patients improved significantly more than the control group on quality of life within three months. Functional status and survival did not differ between groups. A subsample of lung cancer patients provided cross-validation of findings. Although survival was not expected to differ, it was predicted that functioning would be enhanced if quality of life improved. One interpretation is that little can be done to alter physical function and survival when intervention occurs late in the progression of a fatal disease. This in no way reduces the value of improving overall quality of life, since enhancing the quality of survival for end-stage cancer patients is a high priority medical goal. The purpose of the present study was to determine the safety and efficacy of induction chemotherapy followed by concomitant chemoradiotherapy. Thirty-eight patients were randomised to receive induction chemotherapy, consisting of cyclophosphamide and methotrexate followed by concomitant 5-fluorouracil and irradiation (study group) or irradiation alone (control group). There were non-significant differences in the initial tumor clearance rates in the two groups. Median disease-free survival (in complete responders) was 17 months (6-60+) vs 11 months (5-60+) (p = 0.407) and overall survival 11 months (1-60+) vs 14 months (2-60+) (p = 0.428) in the study and control groups respectively. Acute morbidity and deaths during intervention were higher in the study group (p = 0.007). This study suggests that induction along with concomitant chemoradiotherapy is too toxic for routine use and also fails to provide a survival benefit. The European Lung Cancer Working Party (ELCWP) designed a 3-arm phase III randomised trial to determine the role of accelerated chemotherapy in extensive-disease (ED) small-cell lung cancer (SCLC). Eligible patients were randomised between the 3 following arms: (A) Standard chemotherapy with 6 courses of EVI (epirubicin 60 mg m(-2), vindesine 3 mg m(-2), ifosfamide 5 g m(-2); all drugs given on day 1 repeated every three weeks. (B) Accelerated chemotherapy with EVI administered every 2 weeks and GM-CSF support. (C) Accelerated chemotherapy with EVI and oral antibiotics (cotrimoxazole). Primary endpoint was survival. 233 eligible patients were randomised. Chemotherapy could be significantly accelerated in arm B with increased absolute dose-intensity. Best response rates, in the population of evaluable patients, were, respectively for arm A, B and C, 59%, 76% and 70%. The response rate was significantly higher in arm B in comparison to arm A (P = 0.04). There was, however, no survival difference with respective median duration and 2-year rate of 286 days and 5% for arm A, 264 days and 6% for arm B and 264 days and 6% for arm C. Severe thrombopenia occurred more frequently in arm B but without an increased rate of bleeding. Non-severe infections were more frequent in arm B and severe infections were less frequent in arm C. Our trial failed to demonstrate, in ED-SCLC, a survival benefit of chemotherapy acceleration by using GM-CSF support. To perform a randomized study of the optimal timing of thoracic radiation (RT) as accelerated hyperfractionated radiation therapy (ACC HFX RT) in combination with concurrent chemotherapy (CHT) in limited-stage small-cell lung cancer (SCLC).
                Between 1988 and 1992, 107 patients were enrolled and 103 were assessable. All patients received ACC HFX RT with 1.5 Gy twice daily to 54 Gy plus concurrent daily carboplatin/etoposide (C/E) (30 mg each) and four sequential cycles of cisplatin/etoposide (PE) (30 mg/m2 and 120 mg/m2, respectively, on days 1 to 3). Group I patients (n = 52) received concurrent chemoradiation at weeks 1 to 4, and group II (n = 51) at weeks 6 to 9. Patients who showed a complete response (CR) or partial response (PR) underwent prophylactic cranial irradiation (PCI) at weeks 16 to 17.
                The median survival time was 34 months in group I and 26 months in group II, and the Kaplan-Meier 5-year survival rates were 30% and 15%, respectively. The difference was almost significant on univariate analysis (P = .052) and was significant on multivariate analysis (P = .027). Group I patients had a significantly higher local control rate than group II patients, but there was no difference between the two groups in distant metastasis rate. There was no difference in the incidence of acute or late grade 3 to 4 toxicity.
                Initial administration of thoracic ACC HFX RT with concurrent C/E seems to produce better local control and survival rates than delayed administration. We have recently reported the psychological outcome of a group Cognitive Behaviour Therapy (CBT) intervention with patients who had metastatic breast cancer. The data of 92 patients who were retained at the first follow-up assessment revealed short-term improvements on measures of mood and self-esteem amongst therapy participants. These changes were not sustained at the 3- and 6-month follow-up assessments. This report describes a survival analysis of 121 patients who entered the study, at 5 years after its commencement. The analysis, based on the Cox Proportional Hazards Regression model, revealed no survival advantage associated with the intervention. Only medical prognostic factors such as Eastern Cooperative Oncology Group (ECOG) performance status, visceral metastases and chemotherapy treatment significantly predicted patients' survival time. The findings of this study are compared with those of two earlier studies which also examined the survival effects of a group psychological intervention with metastatic breast cancer patients.
                Copyright 1999 John Wiley & Sons, Ltd. To compare the length of survival and quality of life in patients given combination chemotherapy in addition to supportive care and in patients given only supportive care.
                Randomised study.
                Gastrointestinal oncology departments.
                40 previously untreated patients with histologically confirmed, measurable colorectal cancer that was locally recurrent or metastatic.
                Patients were allocated randomly to receive chemotherapy or only supportive care in a ratio of 2:1 according to performance status, metastatic disease of the liver, and weight loss in the six months before entering the study. Chemotherapy consisted of four week cycles of intravenous leucovorin (200 mg/m2/day) followed by 5-fluorouracil (550 mg/m2/day) and cisplatin (20 mg/m2/day), each drug being given on the first four days of the cycle.
                Length of survival and quality of life score with an optimised functional living index-cancer scale.
                Overall survival was significantly longer for patients given chemotherapy (11.0 months) than for those receiving supportive care alone (5.0 months; p = 0.006). Despite common association of chemotherapy with mild to moderate gastrointestinal symptoms, there was no significant difference between the two groups in global or subgroup quality of life scores. In patients with abnormal scores before treatment, quality of life seemed better in the chemotherapy arm.
                In this sample of patients with disseminated colorectal cancer the chemotherapy regimen was an effective form of palliative treatment. A Nordic multicenter study in asymptomatic patients with advanced colorectal cancer compared initial chemotherapy with sequential methotrexate-5-FU with leucovorin rescue (MFL) for 6 months versus primary expectancy with chemotherapy only after the appearance of symptoms. The study (183 patients randomized between January 1985 and February 1990) showed that symptom-free survival, progression-free survival and survival respectively were about 6 months longer in the group of patients randomized to initial MFL. Whether these prolongations could be achieved without an impaired 'quality of life' was studied in an associated study. Between January 1985 and March 1987, 43 patients were randomized at one of the hospitals, 36 of which were interviewed with a questionnaire at randomization. Even if all these patients were considered, by the physician, to be 'free of symptoms from their disease', 16/36 (44%) had symptoms that could be referred to the disease. In spite of this, the patients were in a good general condition, and considerably better off than patients considered to have 'symptoms from the disease' who were interviewed with the same questionnaire when randomized in a parallel study of symptomatic patients. Patients randomized to initial chemotherapy and interviewed longitudinally maintained their good condition throughout treatment. Toxicity was mild, although the patients expressed more adverse effects than the physicians recorded. Since symptom-free survival, progression-free survival and survival were statistically significantly longer in the group of patients randomized to MFL also in this associated study, it is concluded that initial chemotherapy can prolong symptom-free survival and survival without reduced 'quality of life' during the treatment period. The Head and Neck Intergroup conducted a phase III randomized trial to test the benefit of adding chemotherapy to radiation in patients with unresectable squamous cell head and neck cancer.
                Eligible patients were randomly assigned between arm A (the control), single daily fractionated radiation (70 Gy at 2 Gy/d); arm B, identical radiation therapy with concurrent bolus cisplatin, given on days 1, 22, and 43; and arm C, a split course of single daily fractionated radiation and three cycles of concurrent infusional fluorouracil and bolus cisplatin chemotherapy, 30 Gy given with the first cycle and 30 to 40 Gy given with the third cycle. Surgical resection was encouraged if possible after the second chemotherapy cycle on arm C and, if necessary, as salvage therapy on all three treatment arms. Survival data were compared between each experimental arm and the control arm using a one-sided log-rank test.
                Between 1992 and 1999, 295 patients were entered on this trial. This did not meet the accrual goal of 362 patients and resulted in premature study closure. Grade 3 or worse toxicity occurred in 52% of patients enrolled in arm A, compared with 89% enrolled in arm B (P <.0001) and 77% enrolled in arm C (P <.001). With a median follow-up of 41 months, the 3-year projected overall survival for patients enrolled in arm A is 23%, compared with 37% for arm B (P =.014) and 27% for arm C (P = not significant).
                The addition of concurrent high-dose, single-agent cisplatin to conventional single daily fractionated radiation significantly improves survival, although it also increases toxicity. The loss of efficacy resulting from split-course radiation was not offset by either multiagent chemotherapy or the possibility of midcourse surgery. Since chemotherapy for metastatic breast cancer is not curative, consideration of the quality of life is important in selecting a treatment regimen. We conducted a randomized trial comparing continuous chemotherapy, administered until disease progression was evident, with intermittent therapy, whereby treatment was stopped after three cycles and then repeated for three more cycles only when there was evidence of disease progression. Each approach was tested with doxorubicin combined with cyclophosphamide or with cyclophosphamide combined with methotrexate, fluorouracil, and prednisone. Intermittent therapy resulted in a significantly worse response (P = 0.02 by Mann-Whitney test), a significantly shorter time to disease progression (relative risk based on proportional-hazards model, 1.8; 95 percent confidence interval, 1.4 to 2.4), and a trend toward shorter survival (relative risk, 1.3; confidence interval, 0.99 to 1.6). The quality of life was expressed as linear-analogue self-assessment scores for physical well-being, mood, pain, and appetite and as a quality-of-life index. It improved significantly during the first three cycles, when all patients received treatment. Thereafter, intermittent therapy was associated with worse scores for physical well-being (by 23 percent of scale; 95 percent confidence interval, 11 to 35 percent), mood (25 percent; 13 to 37 percent), and appetite (12 percent; 0 to 24 percent) and for the quality-of-life index as indicated by the patient (14 percent; 5 to 23 percent) and the physician (16 percent; 7 to 26 percent). Changes in the quality of life were independent prognostic factors in proportional-hazards models of subsequent survival. We conclude that, as tested, continuous chemotherapy is better than intermittent chemotherapy for advanced breast cancer. In an attempt to decrease the toxic effects of fluorouracil, doxorubicin, and methotrexate (FAMTX) by reducing the dose of methotrexate from 1500 mg/m2, according to the original regimen, to 1000 mg/m2, the authors designed the modified FAMTX treatment that was evaluated in a prospective Phase II-III randomized trial.
                Patients with advanced gastric cancer were randomized to receive modified FAMTX treatment or supportive measures only (control group). In the middle of the study, the randomization was interrupted because of strong evidence of benefit in terms of tumor reduction and projected survival in the treatment arm receiving chemotherapy. By the end of the study, 30 assessable patients had received chemotherapy and 10 had received supportive treatment.
                The overall response rate was 50% (15 patients); 12 patients (40%) had partial responses and 3 (10%) had complete responses (CR). One patient with extensive peritoneal carcinomatosis attained a CR pathologically documented by laparoscopic examination and peritoneal biopsy. The median overall survival time of the treated group was 9 months, whereas that of the control group was only 3 months (P = 0.001). The median overall survival time of the responders was 16 months, and their median remission duration was 8 months. The regimen was well tolerated, with a very acceptable toxicity profile. There was one toxic death resulting from neutropenia and sepsis in a patient who did not receive adequate leucovorin rescue.
                This regimen appears to prolong survival in patients with advanced gastric cancer, and the reduction of the methotrexate dose does not seem to compromise its efficacy. The Southwest Oncology Group (SWOG) colorectal adjuvant study 7510 went through two phases. From 1975 to 1977, 309 patients were randomized to chemotherapy alone or the same chemotherapy plus immunotherapy. From 1977 until 1980, 317 patients were randomized among the same two therapy programs and a control group. With a minimum follow-up in either phase of greater than 7 years, data are now mature. They show no difference in relapse-free survival (RFS) nor overall survival (OS) in either the two-way phase or in the three-way phase. There is no indication, except possibly in one very small subset, that the addition of immunotherapy to chemotherapy provides an improvement in OS or in RFS. Using data from patients accrued after randomization to the control group, we fail to find evidence that either chemotherapy alone or chemoimmunotherapy improves OS or RFS when contrasted to outcomes obtained by patients on the control arm. In fact, we have significant evidence, at the P = .016 level, that chemotherapy does not improve OS by at least 50%; we also have significant evidence, at the P = .011 level, that chemoimmunotherapy will not improve OS by at least 25%. No evidence of efficacy was demonstrated for either treatment regimen, even though enough therapy was given to result in significant toxicities. Acute toxicity was at least moderate, but not fatal, in 75% of patients. Recognizable delayed toxicity included rare cases of fatal renal failure and acute leukemia. We have studied the clinical impact of elective brain irradiation (EBI) in patients with locally advanced, non-small cell lung cancer (LA-NSC). All patients received combination chemotherapy (cyclophosphamide + doxorubicin (Adriamycin) + cisplatin = CAP) or CAP plus radiotherapy as the initial treatment for their active tumor or as an adjuvant therapy. Of 97 evaluable patients, 46 were randomized to receive EBI (3 000 rad in 10 fractions given over two weeks). The characteristics of both groups were comparable by sex, age, performance status, pretherapy weight loss, histologic cell type, clinical staging, and type of prior therapy. EBI significantly decreased the incidence of central nervous system (CNS) metastasis in the treated group compared to the control group (4% vs 27%, p = .002). CNS involvement occurred in the treated group after failure at other sites whereas 12 of 14 control patients had CNS metastases as the first site of relapse. EBI decreased the incidence of CNS metastasis in all prognostic categories. Using multivariate analysis, the beneficial effect was shown to be significant in females, patients with good performance status, weight loss less than 6%, squamous cell histology, state III disease or no prior therapy. EBI significantly increased CNS metastasis-free interval with a beneficial effect that was significant in males, patients with weight loss less than 6%, squamous cell histology or responders. Although no survival benefit was observed for the treated group because of the adverse effect from other relapses, EBI will become more important as better treatment programs are developed.(ABSTRACT TRUNCATED AT 250 WORDS) Seventy-one patients with complete hydatidiform mole were prospectively randomized into two groups: one group (39 patients) was treated with a single course of methotrexate and citrovorum factor rescue as chemoprophylaxis; the other group (32 patients) was not treated. After molar evacuation, four patients from the treated group (10.3%) and ten patients from the untreated group (31.3%) developed persistent trophoblastic disease. The time interval from evacuation of the mole to diagnosis of persistent trophoblastic disease was longer in the treated group than in the untreated group (9.5 +/- 2.4 weeks versus 5.1 +/- 1.6 weeks, P less than .05). Among high-risk patients, there was a lower incidence of persistent trophoblastic disease in the treated group than in the untreated group (14.3 versus 47.4%, P less than .05). Among low-risk patients there was no difference between the groups (5.6 versus 7.7%, P greater than .05). All 14 patients with persistent trophoblastic disease achieved complete remission with therapeutic chemotherapy. More courses of chemotherapy were required until complete remission in the treated group than in the untreated group (2.5 +/- 0.5 versus 1.4 +/- 0.5, P less than .005). These findings suggest that even though chemoprophylaxis reduces the incidence of persistent trophoblastic disease in patients at high risk, it increases tumor resistance and morbidity. Although prophylactic chemotherapy with methotrexate and citrovorum factor rescue may be helpful for high-risk patients who cannot be followed or whose compliance is in question, careful follow-up remains the most important way to identify patients who should receive chemotherapy. The aim of the present trial was to evaluate the effects of chemotherapy on the quality of life and survival of patients with advanced non-small cell lung cancer (NSCLC) (stage IIIB or IV). In a controlled multicentre trial, patients were randomised to receive supportive care only or supportive care plus chemotherapy. Chemotherapy consisted of intravenous (i.v.) carboplatin 300 mg/m2 on day 1 and etoposide 120 mg/m2 orally on days 1-5 every 4 weeks for a maximum of eight courses. Quality of life was measured at randomisation and prior to each treatment course and at corresponding 4-week intervals in the control arm, using the EORTC QLQ-C30 + LC13 questionnaire. 48 patients were randomised (supportive care 26, chemotherapy 22), being eligible for comparative analyses. Another 102 patients, 97 of which received chemotherapy, were subsequently included in the study on an individual treatment preference basis. Data from these patients were used for confirmative purposes. Patients in the chemotherapy group reported better overall physical functioning and symptom control compared with the supportive care group. Group differences were smaller within the psychosocial domain, although trends were seen in favour of the chemotherapy group. No significant differences were seen in favour of the supportive care group, except for hair loss. Median survival times were 29 weeks in the chemotherapy group versus 11 weeks in the supportive care group, and 1-year survival rates were 28% versus 8%. Quality of life and survival outcomes were similar in the randomised and non-randomised patients receiving chemotherapy. No treatment-related deaths occurred. In conclusion, treatment with carboplatin and etoposide can improve both the quality of life and the survival of patients with advanced NSCLC. This study, a phase III multicenter randomized trial opened by ECOG in April 1983 and closed in June 1986 was designed to evaluate whether a combination of doxorubicin and an intravenous formulation of diethylstilbestrol diphosphate (DES) was superior to doxorubicin alone in men with hormone refractory prostate cancer. All patients received doxorubicin at a dose of 50 mg/m2 iv every 3 wk either alone or with 1 g DES iv daily for 5 d followed by 1 g iv twice weekly for four cycles (12 wk). The 51 evaluable patients with visceral metastases displayed a significantly increased response rate (27% vs 63%) on the combined therapy arm (p = 0.04). However, the 111 evaluable patients with osseous disease exhibited no difference in response rate between either arm with a p-value of >0.99. Similarly, clinical response rates revealed no difference between the two arms. Cases of cardiac toxicity graded as severe, life threatening, or lethal in the combined therapy arm were 10 times more frequent in the combined-therapy arm than in the doxorubicin-alone group (6.75% compared to 0.7%). This difference was statistically significant (p = 0.0041). All of the cases of superficial and deep venous thrombosis occurred on the combined-therapy arm. There were no other significant differences in the numbers of grade 3 or 4 toxic events. The most common toxicity was hematologic. Failure-free survival duration did reach statistical significance in the combined-therapy group (p = 0.012), although the actual durations were short (2.6-3.2 mo). There was no difference in overall survival between the two groups. The extent to which chemotherapy may relieve tumour-related symptoms, improve quality of life and prolong survival in patients with gastric cancer is not known in spite of the extensive use of this treatment modality. The aim of this study was to estimate any gain in the quantity and quality of life produced by chemotherapy in these patients.
                Between January 1991 and February 1995, 61 patients with gastric cancer were randomized to either chemotherapy in addition to best supportive care or to best supportive care. Chemotherapy was allowed in the latter group if the supportive measures did not lead to palliation. Chemotherapy was the ELF-regimen consisting of 5-fluorouracil, leucovorin and etoposide, or, in elderly patients with poor performance, a 5-fluorouracil/leucovorin regimen (FLv). Quality of life was evaluated with the EORTC-QLQ-C30 instrument.
                More patients in the chemotherapy group (45%, 14/31) had an improved or prolonged high quality of life for a minimum period of 4 months compared to those in the best supportive care group (20%, 6/30, P < 0.05). A similar difference was seen in the treating physician's evaluation of whether the patient was subjectively improved or continued to do well for at least 4 months (17/31, 55% versus 6/30, 20%, P < 0.01). Overall survival was longer in the chemotherapy group (median 8 vs. 5 months) although the difference was not statistically significant (P = 0.12). After corrections for imbalances in pretreatment characteristics, chemotherapy treatment was, however, associated with a survival benefit (P = 0.003). Also, the quality-adjusted survival time and time to disease progression were longer for patients randomized to chemotherapy (median 5 vs. 2 months, P = 0.03).
                The results show that chemotherapy can add to both quantity and quality of life in advanced gastric cancer. The number of patients who benefit from treatment is, however, still rather limited. We report the results of a randomized trial carried out by the Swiss Group for Clinical Cancer Research (SAKK) and in which 230 patients with advanced breast cancer receiving concurrently a hormonal treatment (oophorectomy for pre- and tamoxifen for postmenopausal women) were randomly allocated to three different regimens of combination chemotherapy. The therapeutic results registered with the two more intensive combinations (LMP/FVP and LMFP/ADM) were similar with regard to response rates, time to progression and survival. The patients receiving the low-dose chemotherapy lmfp showed a statistically significant lower response rate (32%, P less than 0.001) and a shorter survival (P = 0.03) than the results observed in patients treated with the two other regimens. This difference was particularly pronounced, at least regarding survival, in the following subgroups: postmenopausal women, patients with a poor performance status, dominant visceral lesions, two sites of disease and a disease-free interval longer than 12 months. Patients with bony metastases as dominant lesion fared similarly with all three regimens of chemotherapy. This latter subset of advanced breast cancer patients should probably be spared too intensive cytotoxic treatment. This is, to our knowledge, the first report of a randomized trial showing an evident correlation between response rate and survival in various subgroups of patients with advanced breast cancer treated with different chemotherapeutic regimens. A prospective randomized multicenter trial was performed to evaluate the contribution of simultaneously administered chemotherapy (CT) and radiotherapy (RT) in previously untreated patients with unresectable stage III/IV head and neck cancer.
                Patients with locoregionally advanced head and neck cancer were treated either with RT alone (arm A) or simultaneous RT plus CT (RCT; arm B). RT was identical in both arms and administered in three courses with 13 fractions of 1.8 Gy each twice daily. During one course, from day 3 to 11, 23.4 Gy was delivered. In arm B, cisplatin (CDDP) 60 mg/m2, fluorouracil (5-FU) 350 mg/m2 by intravenous (i.v.) bolus, and leucovorin (LV) 50 mg/m2 by i.v. bolus were given on day 2, and 5-FU 350 mg/m2/24 hour by continuous infusion and LV 100 mg/m2/24 hours by continuous infusion were given from day 2 to 5. Treatment was repeated on days 22 and 44; a total RT dose of 70.2 Gy was administered. Treatment breaks were scheduled from days 12 to 21 and days 34 to 43.
                From 1989 to 1993, 298 patients were enrolled and 270 patients were assessable. Acute mucositis grade 3 or 4 was more frequent in arm B (38%) than in arm A (16%) (P < .001). Total treatment time was significantly longer in arm B than in arm A (P < .001) due to prolonged breaks. According to hematologic toxicity, scheduled drug doses were given in 74% of patients for the second course and 46% for the third course. The 3-year overall survival rate was 24% in arm A and 48% in arm B (P < .0003). The 3-year locoregional control rate was 17% in arm A and 36% in arm B (P < .004). Both arms showed similar distant failure patterns (arm A, 13 of 140; arm B, 12 of 130). Serious late side effects were not significantly different between treatment arms (arm A, 6.4%; arm B, 10%; not significant).
                Concomitant CT offered improved disease control and survival in advanced head and neck cancer patients. Due to increased acute toxicity, more supportive care is demanded when CT is given simultaneously. Increased total treatment time does not exert a negative impact on outcome in this combined modality regimen. This randomized controlled trial aimed to determine whether an interactive CD-ROM improved cancer patients' recall of chemotherapy treatment information over standard written information, and whether demographic, cognitive, and psychological factors better predicted recall than this format of delivery.
                One-hundred-and-one new patients about to commence chemotherapy were randomized to receive written information or a CD-ROM containing treatment information before giving informed consent. Patients' recall, concentration, short-term memory, reading comprehension, anxiety, depression, and coping styles were assessed with standardized measures pre-treatment. Seventy-seven patients completed tests for recall of treatment information before their second chemotherapy session.
                Intention-to-treat analyses indicated no significant differences between the written information and CD-ROM groups across recall questions about number of drugs received (p=.43), treatment length (p=.23), and treatment goal (p=.69). Binary logistic regressions indicated that for groups combined different variables predicted each of the recall questions.
                An interactive CD-ROM did not improve cancer patients' recall of treatment information enough to warrant changes in consent procedures.
                Different variables predicted recall of different treatment aspects highlighting the complex nature of attempting to improve patient recall. Attending to the effect of depression on patient knowledge and understanding appears paramount. To investigate the impact of dietary counseling or nutritional supplements on outcomes in cancer patients: nutritional, morbidity, and quality of life (QoL) during and 3 months after radiotherapy.
                A total of 111 colorectal cancer outpatients referred for radiotherapy, stratified by staging, were randomly assigned: group 1 (G1; n = 37), dietary counseling (regular foods); group 2 (G2; n = 37), protein supplements; and group 3 (G3; n = 37), ad libitum intake. Nutritional intake (diet history), status (Ottery's Subjective Global Assessment), and QoL (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire version 3.0) were evaluated at baseline, at the end, and 3 months after radiotherapy.
                At radiotherapy completion, energy intake increased in G1/G2 (P < or = .04), G1 more than G2 (P = .001), and decreased in G3 (P < .01). Protein intake increased in G1/G2 (P < or = .007), G1 less than G2 (not significant), and decreased in G3 (P < .01). At 3 months, G1 maintained nutritional intake and G2/G3 returned to baseline. After radiotherapy and at 3 months, rates of anorexia, nausea, vomiting, and diarrhea were higher in G3 (P < .05). At radiotherapy completion, in G1 all QoL function scores improved proportionally to adequate intake or nutritional status (P < .05); whereas in G2 only three of six function scores improved proportionally to protein intake (P = .04), and in G3 all scores worsened (P < .05). At 3 months, G1 patients maintained/improved function, symptoms, and single-item scores (P < .02); in G2, only few function and symptom scales improved (P < .05); in G3, QoL remained as poor as after radiotherapy. In G1/G2, respectively, improvement/deterioration of QoL correlated with better or poorer intake or nutritional status (P < .003).
                During radiotherapy, both interventions positively influenced outcomes; dietary counseling was of similar or higher benefit, whereas even 3 months after RT, it was the only method to sustain a significant impact on patient outcomes. Mixed reports exist about the impact of supportive-expressive group therapy (SEGT) on survival.
                From 485 women with advanced breast cancer recruited between 1996-2002, 227 (47%) consented and were randomized within an average 10 months of cancer recurrence in a 2:1 ratio to intervention with 1 year or more of weekly SEGT plus three classes of relaxation therapy (147 women) or to control receiving three classes of relaxation therapy (80 women). The primary outcome was survival; psychosocial well-being was appraised secondarily. Analysis was by intention-to-treat.
                SEGT did not prolong survival (median survival 24.0 months in SEGT and 18.3 in controls; univariate hazard ratio for death 0.92 [95% CI, 0.69-1.26]; multivariate hazard ratio, 1.06 [95% CI, 0.74-1.51]). Significant predictors of survival were treatment with chemotherapy and hormone therapy (p<0.001), visceral metastases (p<0.001) and advanced disease at first diagnosis (p<0.05). SEGT ameliorated and prevented new DSM-IV depressive disorders (p = 0.002), reduced hopeless-helplessness (p = 0.004), trauma symptoms (p = 0.04) and improved social functioning (p = 0.03).
                SEGT did not prolong survival. It improved quality of life, including treatment of and protection against depression.
                Copyright (c) 2007 John Wiley & Sons, Ltd. To describe a randomized trial of a cognitive behavioral intervention on reducing symptom severity among patients diagnosed with solid tumors and undergoing a first course of chemotherapy and to determine whether the intervention had an additive or interactive effect on symptom severity in the presence of supportive care medications.
                Patients (N = 237) were accrued from comprehensive and community cancer centers, interviewed, and randomly assigned to either the experimental intervention (n = 118) or conventional care (n = 119). A symptom severity index, based on summed severity scores across 15 symptoms, was the primary outcome. Each patient's site of cancer, stage at diagnosis, chemotherapy protocols, and use of supportive medications were learned from medical records.
                Groups were equivalent at baseline, and attrition by characteristics by group was not different. The proportion of patients not receiving chemotherapy at 10 and 20 weeks did not differ by group. At the 10- and 20-week observations, there was a significant interaction between the experimental group and baseline symptom severity. Patients in the experimental group who entered the trial with higher symptom severity reported significantly lower severity at 10 and 20 weeks. Controlling for chemotherapy treatment status at follow-up and supportive care medications did not alter the effect of the experimental intervention.
                Compared with conventional care alone, the experimental intervention was effective among patients who entered the trial with higher levels of symptom severity. Age, sex, site or stage of cancer, and supportive medications did not modify the effect of this cognitive behavioral intervention on symptom severity. Endometrial cancer patients with high grade tumours, deep myometrial invasion or advanced stage disease have a poor prognosis. Randomised studies have demonstrated the prevention of loco-regional relapses with radiotherapy (RT) with no effect on overall survival (OS). The possible additive effect of chemotherapy (CT) remains unclear. Two randomised clinical trials (NSGO-EC-9501/EORTC-55991 and MaNGO ILIADE-III) were undertaken to clarify if sequential combination of chemotherapy and radiotherapy improves progression-free survival (PFS) in high-risk endometrial cancer. The two studies were pooled.
                Patients (n=540; 534 evaluable) with operated endometrial cancer International Federation of Obstetrics and Gynaecology (FIGO) stage I-III with no residual tumour and prognostic factors implying high-risk were randomly allocated to adjuvant radiotherapy with or without sequential chemotherapy.
                In the NSGO/EORTC study, the combined modality treatment was associated with 36% reduction in the risk for relapse or death (hazard ratio (HR) 0.64, 95%confidence interval (CI) 0.41-0.99; P=0.04); two-sided tests were used. The result from the Gynaecologic Oncology group at the Mario Negri Institute (MaNGO)-study pointed in the same direction (HR 0.61), but was not significant. In the combined analysis, the estimate of risk for relapse or death was similar but with narrower confidence limits (HR 0.63, CI 0.44-0.89; P=0.009). Neither study showed significant differences in the overall survival. In the combined analysis, overall survival approached statistical significance (HR 0.69, CI 0.46-1.03; P=0.07) and cancer-specific survival (CSS) was significant (HR 0.55, CI 0.35-0.88; P=0.01).
                Addition of adjuvant chemotherapy to radiation improves progression-free survival in operated endometrial cancer patients with no residual tumour and a high-risk profile. A remaining question for future studies is if addition of radiotherapy to chemotherapy improves the results.
                Copyright 2010 Elsevier Ltd. All rights reserved. The survival benefit of combination chemotherapy to patients with advanced non-small-cell carcinoma of the lung (NSCLC) is controversial. To study this question, the National Cancer Institute of Canada (NCIC) Clinical Trials Group conducted a prospective randomized trial comparing best supportive care (BSC) to two chemotherapy regimens, vindesine and cisplatin (VP), and cyclophosphamide, doxorubicin, and cisplatin (CAP). Between February 1983 and January 1986, 23 centers across Canada entered 251 patients on study. Eighteen centers participated in the three-arm schema (150 patients); centers choosing not to participate in a study with a no-chemotherapy arm followed a two-arm schema comparing VP with CAP (101 additional patients). Altogether, 233 patients were eligible. Patients had measurable or evaluable disease, with either distant metastases (82.5%) or bulky limited disease considered inoperable or unsuitable for radical radiotherapy. The treatment groups were comparable in terms of age, sex, performance status, histology, disease extent, and weight loss. The overall response rates (complete response [CR] plus partial response [PR]) on the chemotherapy arms were CAP, 15.3%, and VP, 25.3% (P = .06). Patients on the three-arm portion of the trial had a median survival of 32.6 weeks when treated with VP, 24.7 weeks with CAP, and 17 weeks with BSC. The significance of the differences in survival, adjusted for prognostic factors, is as follows: chemotherapy v BSC, P = .02; VP v BSC, P = .01; and CAP v BSC, P = .05. Toxicity on the chemotherapy arms was significant, with leukopenia of severe or greater degree occurring in 37.8% (CAP) and 40.0% (VP), severe vomiting in 12.2% (CAP) and 23.3% (VP), and severe neurotoxicity in 15.6% (VP).
ESA treatment in cancer patients increased on study mortality and worsened overall survival. For patients undergoing chemotherapy the increase was less pronounced, but an adverse effect could not be excluded.