Multicenter, randomized comparative trial of fludarabine and the combination of cyclophosphamide-doxorubicin-prednisone in 92 patients with Waldenström macroglobulinemia in first relapse or with primary refractory disease. [Oral levofloxacin versus intravenous ceftriaxone and amoxicillin/clavulanic acid in the treatment of community-acquired pneumonia that requires hospitalization]. Randomized comparison of cyclophosphamide, doxorubicin and cisplatin (CAP) versus cyclophosphamide and doxorubicin (CA) for the treatment of advanced ovarian cancer (ADOVCA). A EORTC Gynecological Cancer Cooperative Group Study. Comparative study of levofloxacin in the treatment of children with community-acquired pneumonia. A randomized prospective comparison of oral levofloxacin plus intraperitoneal (IP) vancomycin and IP netromycin plus IP vancomycin as primary treatment of peritonitis complicating CAPD. Monotherapy with meropenem versus combination therapy with ceftazidime plus amikacin as empiric therapy for fever in granulocytopenic patients with cancer. The International Antimicrobial Therapy Cooperative Group of the European Organization for Research and Treatment of Cancer and the Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto Infection Program. Combination of cyclophosphamide, adriamycin and platinum (CAP) versus 5-fluorouracil, adriamycin and cyclophosphamide (FAC) as primary treatment in metastatic breast cancer: results of a prospective randomized study. Controlled multicenter study with quinapril, hydrochlorothiazide, and combination in patients with moderate to severe hypertension. A controlled trial of a critical pathway for treatment of community-acquired pneumonia. CAPITAL Study Investigators. Community-Acquired Pneumonia Intervention Trial Assessing Levofloxacin. Is monotherapy with cefazolin or ofloxacin an adequate treatment for peritonitis in CAPD patients? [Prophylaxis with fluoroquinolones in patients with neutropenia]. Evaluating treatment strategies in advanced Waldenström macroglobulinemia: use of quality-adjusted survival analysis. A randomized trial of cyclophosphamide, doxorubicin, and prednisone versus cyclophosphamide, 5-fluorouracil, and prednisone in patients with metastatic breast cancer. Intravenous immune globulin (10% caprylate-chromatography purified) for the treatment of chronic inflammatory demyelinating polyradiculoneuropathy (ICE study): a randomised placebo-controlled trial. Quinapril, hydrochlorothiazide, and combination in patients with moderate to severe hypertension. Intravenous cyclosporine versus intravenous corticosteroids as single therapy for severe attacks of ulcerative colitis. A phase III, multicenter, randomized, placebo-controlled clinical trial of topical aminocaproic acid (Caprogel) in the management of traumatic hyphema. Infection prophylaxis in neutropenic patients with acute leukaemia--a randomized, comparative study with ofloxacin, ciprofloxacin and co-trimoxazole/colistin. Trial of co-trimoxazole versus procaine penicillin G and benzathin penicillin + procaine penicillin G in the treatment of childhood pneumonia. Cyclophosphamide, adriamycin and platinum (CAP) combination chemotherapy, a new effective approach in the treatment of disseminated breast cancer. Preliminary report. Granulocyte colony-stimulating factor (G-CSF) with or without a quinolone in the prevention of infection in cancer patients. Interferon alfa and vinblastine versus medroxyprogesterone acetate in the treatment of metastatic renal cell carcinoma. Multicentre prospective randomised trial of fludarabine versus cyclophosphamide, doxorubicin, and prednisone (CAP) for treatment of advanced-stage chronic lymphocytic leukaemia. The French Cooperative Group on CLL.
Few reports are available on the treatment of patients with Waldenström macroglobulinemia (WM) and primary or secondary resistance to alkylating-agent-based regimens. From December 1993 through December 1997, 92 patients with WM resistant to first-line therapy (42) or with first relapse (50) after alkylating-agent therapy were randomly assigned to receive fludarabine (25 mg/m(2) of body-surface area on days 1-5) or cyclophosphamide, doxorubicin (Adriamycin), and prednisone (CAP; 750 mg/m(2) cyclophosphamide and 25 mg/m(2) doxorubicin on day 1 and 40 mg/m(2) prednisone on days 1-5). The first end point evaluated was the response rate after 6 treatment courses. Forty-five patients received CAP and 45 received fludarabine. Two patients died before the first course of chemotherapy. No statistical differences were observed between the 2 treatment arms with respect to hematologic toxicity or infections. Mucositis and alopecia occurred significantly more often in patients treated with CAP. Partial responses were obtained in 14 patients (30%) treated with fludarabine and 5 patients (11%) treated with CAP (P =.019). Responses were more durable in patients treated with fludarabine (19 months versus 3 months), and the event-free survival rate was significantly higher in this group (P <.01). Forty-four patients died, 22 in the fludarabine group and 22 in the CAP group. There was no statistical difference in the median overall survival time in the 2 study arms. Fludarabine was thus more active than CAP in salvage therapy of WM and should be tested as first-line therapy in a randomized comparison with alkylating agents. Levofloxacin, an antibiotic from the quinolone family, which is used with success in the ambulatory treatment of patients with community-acquired pneumonia, has been recently introduced to the pharmaceutical market. The purpose of this study was to compare the effectiveness and tolerance of oral (v.o.) levofloxacin (LVF) versus intravenous (i.v.) amoxicillin/clavulanate (AMX/CL) and ceftriaxone (CTX) in the treatment of the community-acquired pneumonia that require hospitalization (CAPH).
                In this prospective and randomized study 84 patients were included, 28 per group, from both sex with CAPH. The patients were assigned randomly to receive one of the next treatments: AMX/CL, 1.02 g i.v. every 8 h, CTX, 1 g i.v. every 12 h or LVF, 500 mg v.o. every 24 h. At the beginning clinical, biochemical and radiological characteristics were recorded from each case and at the 72 h the effect of treatment was evaluated using the evolution of the thermal curve and radiological images. The quantitative variables were analyzed with ANOVA, the qualitatives parameters with *2 test and Yates correction. The level of signification was * = 0.05.
                Age, sex, clinical presentation, biochemical measurements and radiological images in the 3 groups were similar and no adverse effects were recorded in any of them. Number of patients with favorable outcome in the groups AMX/CL, CTX and LVF was 25 (89%), 25 (89%) and 26 (93%); p = 0,870.
                Levofloxacin can be a simple, effective and safe therapeutic option for patients with CAPH. The possible advantage of adding cisplatin (P) to cyclophosphamide (C) + adriamycin (A) in the management of stages III and IV ovarian cancer of epithelial origin was tested in a trial in which 149 patients were randomized to receive, after initial surgery, either CAP (C = 600 mg/sqm, A = 45 mg/sqm, P = 50 mg/sqm) or CA (C = 600 mg/sqm, A = 45 mg/sqm) every 4 weeks for 6 to 12 cycles, at which time follow-up laparotomoy was to be performed in responding or clinically disease-free patients. Fifteen patients were not included in the final analysis and the remaining 134 patients were considered fully or partially evaluable and are used in analysis of response and survival. The complete and partial response rates were 45.6% in the CAP arm and 45.4% in the CA arm, but the CAP regimen is of special importance in patients with bulky disease. Median survival CAP = 24 m and CA = 24.2 m), time to progression and survival was found not significantly different when CAP and CA were compared. However, more patients in the CA regimen had no macroscopic disease left after surgery than in CAP regimen (11 versus 6) and more patients in the CAP arm dose reductions and schedule delays than in the CA arm (61.1% versus 38.2%). Levofloxacin has established efficacy and safety in the treatment of community-acquired pneumonia (CAP) in adults, and its use as an alternative therapy for children with CAP has been proposed.
                Assess the clinical efficacy and safety of levofloxacin compared with standard of care antibiotic therapy in the treatment of CAP in children aged 6 months to 16 years.
                In an open-label, multicenter, noninferiority trial, children with CAP were randomized 3:1 to receive levofloxacin or comparator antimicrobial therapy (0.5 to <5 years: amoxicillin/clavulanate or ceftriaxone; > or =5 years: clarithromycin or ceftriaxone with clarithromycin or erythromycin lactobinate) for 10 days. The primary outcome was cure rates at the test-of-cure visit (10-17 days after completing treatment) as determined by symptoms, physical examination, and chest radiography.
                Seven hundred and thirty-eight children were enrolled and 539 (405 levofloxacin-treated, 134 comparator-treated) were clinically evaluable at test-of-cure visit. Clinical cure rates were 94.3% (382 of 405) in levofloxacin-treated and 94.0% (126 of 134) in comparator-treated children. Cure rates were also similar for levofloxacin and comparator for each age group (<5 years, 92.2% versus 90.8%; > or =5 years, 96.5% versus 97.1%; respectively) and for children categorized as being at higher risk for severe disease. Mycoplasma pneumoniae was the most frequently identified cause of pneumonia (230 children). Levofloxacin was as well tolerated as comparators, with similar type and incidence of adverse events.
                Levofloxacin was as well tolerated and effective as standard-of-care antibiotics for the treatment of CAP in infants and children. To compare the therapeutic efficacy of daily oral levofloxacin plus intermittent intraperitoneal (IP) vancomycin (group 1) versus daily IP netromycin and intermittent IP vancomycin (group 2) in the primary treatment of peritonitis complicating continuous ambulatory peritoneal dialysis (CAPD).
                A randomized multicenter prospective open-label comparative clinical study.
                University and Hospital Authority hospitals in Hong Kong.
                All CAPD patients who developed bacterial or culture-negative peritonitis beyond 28 days of a previous episode and without evidence of septicemia, associated tunnel infection, or known sensitivity to trial medications were accepted into the clinical trial.
                A total of 101 patients entered the trial. The primary cure rate was 74.5% for group 1 and 73.6% for group 2. Baseline culture results appeared to influence the clinical outcome: the primary cure rate for culture-negative, gram-positive, and gram-negative episodes was 83.3%, 78.6%, and 42.9% for group 1 and 69.1%, 76.9%, and 71.3% for group 2, respectively. The primary cure rate also varied considerably among individual centers and was particularly noticeable in group 1. In the latter group, it correlated closely with in vitro levofloxacin resistance which in turn correlated closely with previous exposure to fluoroquinolones.
                Oral levofloxacin in combination with intermittent IP vancomycin has comparable efficacy to IP netromycin combined with intermittent IP vancomycin as primary treatment in CAPD peritonitis, but is simpler and more cost-effective to administer. It may be recommended as primary therapy in centers with relatively low exposure and, therefore, low background resistance to fluoroquinolones. Combinations of beta-lactams plus aminoglycosides have been standard therapy for suspected infections in granulocytopenic cancer patients, especially those with profound long-lasting granulocytopenia. With the advent of new broad-spectrum bactericidal antibiotics such as extended-spectrum cephalosporins or carbapenems, the need to combine beta-lactams with aminoglycosides became more controversial. The objective of this prospective randomized multicenter study was to compare the efficacy, safety, and tolerance of meropenem monotherapy with those of the combination of ceftazidime plus amikacin for the empirical treatment of fever in granulocytopenic cancer patients. Of 1,034 randomized patients, 958 were assessable in the intent-to-treat analysis for response to antibacterial therapy, including 483 in the meropenem group and 475 in the ceftazidime-plus-amikacin group. The median durations of neutropenia were 16 and 17 days, respectively. A successful outcome was reported in 270 of 483 (56%) patients treated with monotherapy compared with 245 of 475 (52%) patients treated with the combination group (P = 0.20). The success rates in the monotherapy group and the combination group were similar by type of infection (single gram-negative bacteremia, single gram-positive bacteremia, clinically documented infection, and possible infection). The occurrence of further infections assessed in patients for whom the allocated regimen was not modified did not differ between the two groups (12% in both groups). Mortality due to the presenting infection or further infection was relatively low (8 patients treated with the monotherapy compared with 13 patients treated with the combination). A total of 1,027 patients were evaluable for adverse events; the proportion of those who developed adverse effects was similar between the two groups (29% in both groups), and only 19 (4%) patients in the monotherapy group and 31 (6%) in the combination group experienced an adverse event related or probably related to the study drug. Allergic reactions were the only reason for stopping the protocol antibiotic(s) (3 and 5 patients, respectively). This study confirms that monotherapy with meropenem is as effective as the combination of ceftazidime plus amikacin for the empiric treatment of fever in persistently granulocytopenic cancer patients, and both regimens were well tolerated. Based on favorable results we reported earlier with the CAP regimen in breast cancer (CAP vs CMFVP), the present study compared the CAP with the FAC regimen, which is so far one of the most active adriamycin containing chemotherapy regimens in breast cancer. The aim of the study was to find the optimal first line treatment and possibly evaluate the role of cis platinum in breast cancer chemotherapy. The CAP schedule consisted of cyclophosphamide 200 mg/m2 i.v. days 1, 3 and 5, adriamycin 40 mg/m2 i.v. day 1, and platinum 30 mg/m2 i.v. day 1, 3 and 5. The FAC schedule included 5-FU 500 mg/m2 days 1 and 8, adriamycin 50 mg/m2 day 1, and cyclophosphamide 500 mg/m2 day 1. One hundred and twenty-six previously untreated patients received greater than 2 cycles and were evaluated. In the CAP arm 15 complete (26%) and 24 partial remissions were observed, resulting in a 67% overall response rate (39/58). The response in soft tissue and visceral organs was notable (78% - 22/28, 71% - 15/21) with an important complete response rate (32%). In the FAC arm there was an overall response in 41% (28/68) of patients, with 8 complete (12%) and 20 partial responses. The difference in overall response, complete response, and response in soft tissue and visceral organs, was statistically significant in favor of the CAP arm (P less than 0.005). Concerning bone metastases there was no difference between the two schedules in response rate, nor in the median remission duration (CAP 11, FAC 10 months). In spite of a somewhat longer median survival in the CAP group, the difference (13 months vs 9 months) was not statistically significant (P = 0.10). Toxicity was moderate and tolerable in both regimens with more pronounced myelosuppression and vomiting in the CAP group. Compared with the FAC schedule the platinum containing combination chemotherapy (CAP) showed higher antitumor activity with no reflection on remission duration and survival. In an 8-week, double-blind, randomized, active-controlled, multicenter study with three parallel treatment groups, we compared the efficacy and safety of once-daily 20 mg quinapril plus 12.5 mg hydrochlorothiazide (HCTZ) with each drug as monotherapy in patients with moderate to severe hypertension. Hypertensive out-patients with supine diastolic blood pressure (DBP) > or = 105 and < or = 120 mm Hg at the end of a 2- to 4-week placebo-baseline period were randomly assigned to one of the treatment groups. Of the 323 patients who were randomized to double-blind medication, 297 completed the study, but 6 patients were excluded for violations of protocol; therefore, statistical analysis was performed in 291 patients. Only 7 patients withdrew owing to lack of efficacy (2 receiving combination therapy). In all three treatment groups, clinically significant reductions in DBP were achieved. Combination therapy was statistically more effective than each component in both evaluable data and intent-to-treat analyses. The incidence of adverse events (AE) was 24% in the quinapril monotherapy group, 14% in the combination therapy group, and 11% in the HCTZ monotherapy group. Orthostatic hypotension with related symptoms was observed in 4 patients (2 receiving quinapril monotherapy, 1 receiving HCTZ monotherapy, and 1 receiving combination therapy). Once-daily quinapril plus HCTZ provided increased reduction of DBP as compared with the monotherapies and was well tolerated in patients with moderate to severe hypertension. Large variations exist among hospitals in the use of treatment resources for community-acquired pneumonia (CAP). Lack of a common approach to the diagnosis and treatment of CAP has been cited as an explanation for these variations.
                To determine if use of a critical pathway improves the efficiency of treatment for CAP without compromising the well-being of patients.
                Multicenter controlled clinical trial with cluster randomization and up to 6 weeks of follow-up.
                Nineteen teaching and community hospitals in Canada.
                A total of 1743 patients with CAP presenting to the emergency department at 1 of the participating institutions between January 1 and July 31, 1998.
                Hospitals were assigned to continue conventional management (n = 10) or implement the critical pathway (n = 9), which consisted of a clinical prediction rule to guide the admission decision, levofloxacin therapy, and practice guidelines.
                Effectiveness of the critical pathway, as measured by health-related quality of life on the Short-Form 36 Physical Component Summary (SF-36 PCS) scale at 6 weeks; and resource utilization, as measured by the number of bed days per patient managed (BDPM).
                Quality of life and the occurrence of complications, readmission, and mortality were not different for the 2 strategies; the 1-sided 95% confidence limit of the between-group difference in the SF-36 PCS change score was 2.4 points, which was within a predefined 3-point boundary for equivalence. Pathway use was associated with a 1.7-day reduction in BDPM (4.4 vs 6.1 days; P = .04) and an 18% decrease in the admission of low-risk patients (31% vs 49%; P = .01). Although inpatients at critical pathway hospitals had more severe disease, they required 1.7 fewer days of intravenous therapy (4.6 vs 6.3 days; P = .01) and were more likely to receive treatment with a single class of antibiotic (64% vs 27%; P<.001).
                In this study, implementation of a critical pathway reduced the use of institutional resources without causing adverse effects on the well-being of patients. This prospective randomized study is an evaluation of efficacy of cefazolin and ofloxacin in 23 end-stage renal disease (ESRD) patients treated with continuous ambulatory peritoneal dialysis (CAPD) who experienced 38 episodes of peritonitis (P). Cefazolin was administered intraperitoneally: 1000 mg as loading dose and 250 mg every exchange as maintenance dose for ten days. Ofloxacin was given orally: first 300 mg, followed by ten daily doses of 200 mg. Microbes most frequently isolated from peritoneal effluent were Staphylococci (coagulase-negative in 55.3%, aureus in 7.9%), Acinetobacter (in 5.3%), Klebsiella (in 5.5%), and Micrococcus (in 5.3%). Used as monotherapy, we found the efficacy of both cefazolin and ofloxacin inadequate for treatment of P in CAPD patients (cefazolin 65%, ofloxacin 67%) (NS). In order to evaluate whether the prophylactic use of fluoroquinolones diminishes the incidence of infections and/or mortality during neutropenia, we undertook a prospective, aleatory and controlled study in non-hospitalized adult patients with acute leukemia and chemotherapy-induced neutropenia including twenty five episodes of neutropenia including twenty five episodes of neutropenia which had occurred in 14 patients who were randomly selected either to receive or not quinolones (norfloxacin 800 mg daily or ciprofloxacin 1000 mg daily). Both groups were similar in terms of sex, age, underlying disease, chemotherapy for hematologic malignancy, duration and severity of neutropenia. The use of quinolones was associated with a delay in the fever onset during neutropenia (p = 0.0448), a decrease in the proportion of neutropenic febrile days (p = 0.0456), a decrease of infections caused by gram-negative bacilli (p = 0.037) and an increase of Streptococcus infections (p = 0.0857). There was no significant decrease in mortality, incidence of severe infections, proportion of neutropenic episodes without fever, empiric use of amphotericin B or fungal infections between both groups. The results of this study demonstrate that the prophylactic use of fluoroquinolones does not diminish the infectious morbidity and/or mortality in these patients. A randomized phase II multicenter clinical trial comparing the efficacy of fludarabine (FAMP) to that of the association of cyclophosphamide, doxorubicin and prednisone (CAP) in 92 patients with Waldenstrom's macroglobulinemia in first relapse or with primarily resistant disease, was conducted on the behalf of the 'Groupe Coopératif Macroglobulinémie'. The main analysis of this study failed to demonstrate a clear cut benefit of FAMP in terms of overall survival (OS), although a significant benefit in terms of time to disease progression and event-free survival (EFS) was noted. In this rare disorder, where few randomized trials have been conducted, we took advantage of this trial to assess treatment differences while integrating quality of life considerations. We thus performed a quality-adjusted survival analysis, using the quality-adjusted time without symptoms or toxicity (Q-TWiST) approach. Four health states differing in terms of quality of life (QoL) were defined, namely treatment-related toxicity, treatment free of toxicity, no treatment or symptoms, and relapse. The average time spent in these health states (TOX, CT, TWiST and REL, respectively) were then weighted by utility coefficients reflecting relative QoL value according to that of TWiST and summed up giving the so-called Q-TWiST. No difference was found between randomized groups in terms of mean CT. Mean TOX in the two groups were similarly close except when considering alopecia as a relevant toxic event. By contrast, mean TWiST was 5.9 months longer in the FAMP group than in the CAP group (P = 0.006). Unsurprisingly, given the absence of difference in OS but the difference in EFS in favor of the FAMP group, mean REL was increased by 6.8 months in the CAP group (P = 0.047). As a result, benefit of FAMP in terms of average Q-TWiST only relied on the value of the utility coefficient attributed to REL (U(REL)), with a significant benefit when UREL ranged from 0 to 0.28, ie in patients undergoing poor QoL after relapse, which is likely. Ninety-four patients were entered in a clinical trial assessing the clinical activity of cyclophosphamide, doxorubicin, and prednisone (CAP) versus a combination of cyclophosphamide. 5-Fluorouracil, and prednisone (CFP) in patients with advanced breast cancer. Objective response rates were comparable, 49% for CFP and 46% for CAP. There was no statistical difference between the duration of response of the two regimens or in time to progression. Most importantly, survival differences were not apparent. Both regimens were clinically tolerable and toxicities, for the most part, were comparable. Thus, no therapeutic advantage existed for either of these polychemotherapy regimens in patients with advanced breast cancer. Short-term studies suggest that intravenous immunoglobulin might reduce disability caused by chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) but long-term effects have not been shown. We aimed to establish whether 10% caprylate-chromatography purified immune globulin intravenous (IGIV-C) has short-term and long-term benefit in patients with CIDP.
                117 patients with CIDP who met specific neurophysiological inflammatory neuropathy cause and treatment (INCAT) criteria participated in a randomised, double-blind, placebo-controlled, response-conditional crossover trial. IGIV-C (Gamunex) or placebo was given every 3 weeks for up to 24 weeks in an initial treatment period, and patients who did not show an improvement in INCAT disability score of 1 point or more received the alternate treatment in a crossover period. The primary outcome was the percentage of patients who had maintained an improvement from baseline in adjusted INCAT disability score of 1 point or more through to week 24. Patients who showed an improvement and completed 24 weeks of treatment were eligible to be randomly re-assigned in a blinded 24-week extension phase. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00220740.
                During the first period, 32 of 59 (54%) patients treated with IGIV-C and 12 of 58 (21%) patients who received placebo had an improvement in adjusted INCAT disability score that was maintained through to week 24 (treatment difference 33.5%, 95% CI 15.4-51.7; p=0.0002). Improvements from baseline to endpoint were also recorded for grip strength in the dominant hand (treatment difference 10.9 kPa, 4.6-17.2; p=0.0008) and the non-dominant hand (8.6 kPa, 2.6-14.6; p=0.005). Results were similar during the crossover period. During the extension phase, participants who continued to receive IGIV-C had a longer time to relapse than did patients treated with placebo (p=0.011). The incidence of serious adverse events per infusion was 0.8% (9/1096) with IGIV-C versus 1.9% (11/575) with placebo. The most common adverse events with IGIV-C were headache, pyrexia, and hypertension.
                This study, the largest reported trial of any CIDP treatment, shows the short-term and long-term efficacy and safety of IGIV-C and supports use of IGIV-C as a therapy for CIDP. This 8-week, double-blind, multicentre study compared the efficacy and safety of the combination of quinapril and hydrochlorothiazide (HCTZ) with each drug as monotherapy. Outpatients with moderate to severe hypertension defined as supine diastolic blood pressure (DBP) > or = 105 mmHg and < or = 120 mmHg at the end of a 2 to 4-week placebo-baseline period were randomly assigned to one of the three treatments: once-daily 10 mg quinapril plus 12.5 mg HCTZ or monotherapy with these doses. After 4 weeks, the doses were to be doubled for the remaining 4 weeks. Three hundred and sixty-eight patients were randomized to double-blind medication; 346 completed the study. Seven patients withdrew due to lack of efficacy. Four patients withdrew due to side effects. In all three treatment groups, clinically significant reductions in DBP were achieved. Combination therapy was statistically more effective than each component taken as monotherapy. Adverse events were infrequent in all treatment groups. No patients experienced symptomatic hypotension or orthostatic hypotension. Cyclosporine has been effective in patients with steroid-refractory attacks of ulcerative colitis (UC). We investigated the effects of intravenous (IV) cyclosporine as single IV therapy (without glucocorticosteroids) for severe UC and compared these with the response to glucocorticosteroids.
                Patients with a severe attack of UC were randomized to treatment with IV cyclosporine, 4 mg x kg(-1) x day(-1), or with methylprednisolone, 40 mg/day, in a randomized, double-blind, controlled trial. After 8 days, patients who had a response received the same medication orally in combination with azathioprine. Patients were followed up clinically, endoscopically, and by scintigraphy. Renal function was assessed using urinary inulin clearances. Endpoints were clinical improvement, discharge from the hospital, and remission up to 12 months after intravenous therapy.
                Thirty patients were included. After 8 days, 8 of 15 patients (53%) who received methylprednisolone had a response to therapy vs. 9 of 14 (64%) receiving cyclosporine. In nonresponders, 3 of 7 methylprednisolone patients and 1 of 3 cyclosporine patients improved when both treatments were combined. No serious drug-related toxicity was observed with either treatment. At 12 months, 7 of 9 patients (78%) initially controlled with cyclosporine maintained their remission vs. 3 of 8 (37%) initially treated with methylprednisolone. No clinically significant decrease of renal function was observed.
                Cyclosporine monotherapy is an effective and safe alternative to glucocorticosteroids in patients with severe attacks of UC. To determine the safety and efficacy of topical aminocaproic acid (Caprogel) in the management of traumatic hyphema.
                Multicenter, randomized, double-masked, placebo-controlled clinical trial.
                A total of 51 patients participated in this trial (power = 36%, 2-tailed test).
                Patients presenting with traumatic hyphema were randomly assigned to 5-day treatment with topical aminocaproic acid or a placebo gel. Patients were monitored daily with ocular examination and vital sign testing for the 5 days of treatment and at 24 and 48 hours after treatment. General physical examination and laboratory testing were performed at baseline and day 5.
                The main efficacy variable was the rate of rebleeding. Secondary efficacy variables included time to hyphema clearance, intraocular pressure, time to secondary hemorrhage, and visual acuity. Safety variables included adverse events, vital signs, and laboratory measurements.
                Rebleeding occurred in 30% of the placebo group (8 of 27; 95% confidence interval [CI] = 14-50%), versus 8% of the treatment group (2 of 24; 95% CI = 1-27%), for an estimated continuity-corrected difference in percentage of patients with bleeding of 17% (95% CI = -3-38%). Secondary efficacy variables were similar in the groups, except that there was a trend towards more visual improvement in the topical aminocaproic acid group (54%) than in the placebo group (30%) at the last measurement (P = 0.08). Adverse events were similar.
                This study provides evidence that topical aminocaproic acid is safe and demonstrates trends towards reducing the rebleeding rate in the management of traumatic hyphema. However, because the study was terminated before complete enrollment, more definitive recommendations will require a larger trial. Preliminary results are presented of an ongoing, prospective, randomized, study comparing ofloxacin, ciprofloxacin and co-trimoxazole/colistin for the prevention of infection in patients with acute leukaemia. The results for 59 patients (median age 47 years, range 21-72) included 88 episodes of neutropenia, each associated with a course of cytotoxic therapy. The main factor measured was the time elapsed from the beginning of neutropenia (neutrophils less than 500/microliter) until the first infectious febrile episode. The median time for the period was 12 days (range 1-56) for the cotrimoxazole/colistin group, 15 days (range 1-38) for the ofloxacin group and 20 days (range 1-36) for the ciprofloxacin group (differences not significant). Microbiologically proven major infections occurred in 10/27 treatment courses with co-trimoxazole/colistin 7/31 courses with ofloxacin and 7/30 courses with ciprofloxacin (P not significant). These were mostly due to Gram-positive cocci. There were no Gram-negative infections in the quinolone groups compared with one major Pseudomonas aeruginosa infection in the co-trimoxazole/colistin group. No Pneumocystis carinii infections were encountered. Adverse reactions associated with co-trimoxazole/colistin required discontinuation of medication in 11/27 treatment courses because of compliance problems, skin reactions or gastrointestinal intolerance. There were significantly fewer discontinuations in the ofloxacin (n = 2) and in the ciprofloxacin groups (n = 3). Major side effects of the quinolones included persistent icterus in one patient receiving ofloxacin and psychiatric symptoms in one patient receiving ciprofloxacin. It is concluded from these data that there were no statistically significant differences between the three treatment groups in respect of the prevention of infection.(ABSTRACT TRUNCATED AT 250 WORDS) This study, which aimed to assess the results of three different regimens in the treatment of pneumonia, was carried out at the Pediatric Outpatient Department of Capa Children's Hospital in Istanbul on 151 patients aged between 4 months and 14 years. The first group (n = 46) received co-trimoxazole orally for 10 days and the second group (n = 63) procaine penicillin G in intramuscularly for 10 days. Benzathin penicillin G combined with procaine penicillin G was given to the third group (n = 42) as a single dose intramuscularly. While the best results were obtained with penicillin procaine G, no statistically significant difference was found between this regimen and co-trimoxazole therapy (chi 2 = 0.305023 P = 0.5). We suggest that co-trimoxazole is easy to administer and cost effective in the ambulatory treatment of pneumonia in children. The prospective controlled Phase III clinical trial tested the therapeutic value of the cis-platinum-adriamycin-cyclophosphamide combination (CAP), compared with the combination including cyclophosphamide, methotrexate, 5-fluorouracil, vincristine and prednisolone (CMFVP), in untreated metastatic breast cancer. One hundred and twenty-three patients (greater than 2 cycles) were evaluated: 61 on the CAP, and 62 on the CMFVP schedule. An objective response (CR + PR) to CAP combination chemotherapy was achieved in 72% of patients (43/61), with a high rate (36%) of complete remissions. In terms of metastatic site, the response rate appeared to be particularly high in soft tissue and visceral organ (lung, liver) metastases. In the CMFVP group, an objective response was noted in 26 of 62 patients (42%), with 16% complete remissions. The difference in overall therapeutic response - and in the complete remission rate as well - was statistically significant to the advantage of the CAP regimen (P less than 0.01). The duration of remissions was 6-28 + months (means = 14) for the CAP, and 4-15 + months (mean = 9) for the CMFVP schedule. Toxic side effects were more pronounced in the CAP group, particularly myelosuppression, with anemia prevailing. Side effects of CMFVP treatment were moderate. In 39 CMFVP previously treated cases, CAP was administered as second-line treatment, and an objective response was observed in 51% of cases (20/39). Results of this controlled trial showed the advantage of the CAP combination chemotherapy in the treatment of metastatic breast cancer. 59 patients who had earlier developed an infection following antineoplastic chemotherapy were randomised to receive either granulocyte colony-stimulating factor (G-CSF) alone or G-CSF+quinolone as prophylaxis during subsequent identical chemotherapy courses. 30 patients received 48 courses of G+CSF, while 29 patients received 44 courses of G-CSF+ofloxacin or ciprofloxacin. The overall infection rate was 23%. Patients with WHO grade IV leukopenia at the onset of prophylactic treatment developed infection in 61% of cases when on G-CSF, but only in 22% when on G-CSF+quinolone (P = 0.002). Patients with initial leukopenia of grade WHO III-I had only a 11% infection rate showing no significant difference between the treatment groups. The median duration of leukopenia < 1 x 10(9)/l was 4 days for patients receiving G-CSF alone and 3.5 days for those receiving additional quinolone. Patients developing infection had grade IV leukopenia for a median of 5 days. Both prophylactic treatments were well tolerated. We conclude that when prophylactic G-CSF is initiated at WHO grade IV leukopenia, addition of an oral quinolone reduces the risk of infection. Since the beginning of the 1980s, when gene technology provided sufficient amounts of cytokines, numerous Phase II studies in metastatic renal cell carcinoma were carried out mostly with interferon alfa (IFN-alpha) and interleukin-2 (IL-2). So far, no randomized prospective trials including untreated control groups have been reported. We present a prospective study comparing IFN-alpha and vinblastine (VBL) versus medroxyprogesterone acetate (MPA).
                Immunochemotherapy schedule consists of IFN-alpha 8 million U/day subcutaneously for 3 days per week and VBL 0.1 mg/kg body weight intravenously at 3-week intervals. MPA was administrated intramuscularly at a dosage of 500 mg/week. The response rates, toxicities, and actuarial overall survival were analyzed.
                The overall response rate in 41 patients receiving IFN-alpha and VBL treatment was 20.5% (95% confidence interval, 9% to 33%). Four patients reached a complete and 5 patients reached a partial remission. No remissions were observed in 35 patients of the control group. A statistically significant survival benefit for the IFN-alpha and VBL group could not be demonstrated. Excluding fever, mild to moderate toxicities were observed. About one third of patients refused the proposed schedule due to general malaise and fatigue.
                A survival benefit or a favorable outcome of patients with metastatic renal cell carcinoma, treated with IFN-alpha and VBL, could not be demonstrated. As judged from this analysis, IFN-alpha and VBL therapy does not sufficiently meet the requirements of a palliative treatment of renal cell carcinoma. Fludarabine seems to be a promising treatment for patients with advanced chronic lymphocytic leukaemia (CLL). We compared fludarabine therapy with the combination of cyclophosphamide, doxorubicin, and prednisone (CAP) for treatment of CLL in a randomised, multicentre prospective trial.
                Patients older than 18 years of age were entered into the study if they presented with previously untreated B-cell lineage CLL (B-CLL) of Binet stages B or C or relapsed B-CLL pretreated with chorambucil or similar non-anthracycline-containing regimens. Patients were randomly assigned to either fludarabine (25 mg/m2 per day on days 1-5) or CAP (cyclophosphamide 750 mg/m2 per day and doxorubicin 50 mg/m2 per day on day 1, and prednisone 40 mg/m2 per day on days 1-5), both given for six courses.
                Of 196 evaluable patients, 100 were previously untreated whereas 96 patients had received prior therapy. Remission rates were significantly higher after fludarabine than CAP, with overall response rates of 60% and 44%, respectively (p = 0.023). A higher response rate to fludarabine was observed in both untreated (71% vs 60%, p = 0.26) and pretreated (48% vs 27%, p = 0.036) cases, although the difference was statistically significant only in pretreated cases. In the latter group, remission duration and survival did not differ between treatment groups with a median remission duration of 324 days after fludarabine and 179 days after CAP (p = 0.22) and median survival times of 728 days and 731 days, respectively. In untreated cases, on the other hand, fludarabine induced significantly longer remissions than CAP with the median not yet reached after fludarabine and a median of 208 days after CAP (p < 0.001). This effect also translated into a tendency towards longer overall survival after fludarabine (p = 0.087). Treatment-associated side-effects consisted in both regimens of predominantly myelosuppression and in particular granulocytopenia. CAP-treated patients had a higher frequency and severity of nausea and vomiting (25% vs 5%, p < 0.001) and alopecia (65% vs 2%, p < 0.001).
                Fludarabine provided an effective and well-tolerated therapy for patients with advanced CLL, which compared favourably with CAP as one of the most effective standard regimens. In second-line therapy, fludarabine induced a significantly higher rate of complete and partial remissions, while in first-line therapy a significant prolongation of remission was obtained, which may translate into an improvement of overall survival.
No benefit of survival or clinical efficacy was shown with empirical atypical coverage in hospitalized patients with CAP. This conclusion relates mostly to the comparison of quinolone monotherapy to beta-lactams. Further trials, comparing beta-lactam monotherapy to the same combined with a macrolide, should be performed.