Liposomal cisplatin combined with paclitaxel versus cisplatin and paclitaxel in non-small-cell lung cancer: a randomized phase III multicenter trial.

BACKGROUND: Liposomal cisplatin is a new formulation developed to reduce the systemic toxicity of cisplatin while simultaneously improving the targeting of the drug to the primary tumor and to metastases by increasing circulation time in the body fluids and tissues. The primary objectives were to determine nephrotoxicity, gastrointestinal side-effects, peripheral neuropathy and hematological toxicity and secondary objectives were to determine the response rate, time to tumor progression (TTP) and survival. PATIENTS AND METHODS: Two hundred and thirty-six chemotherapy-naive patients with inoperable non-small-cell lung cancer were randomly allocated to receive either 200 mg/m² of liposomal cisplatin and 135 mg/m² paclitaxel (arm A) or 75 mg/m² cisplatin and 135 mg/m² paclitaxel (arm B), once every 2 weeks on an outpatient basis. Two hundred and twenty-nine patients were assessable for toxicity, response rate and survival. Nine treatment cycles were planned. RESULTS: Arm A patients showed statistically significant lower nephrotoxicity, grade 3 and 4 leucopenia, grade 2 and 3 neuropathy, nausea, vomiting and fatigue. There was no significant difference in median and overall survival and TTP between the two arms; median survival was 9 and 10 months in arms A and B, respectively, and TTP was 6.5 and 6 months in arms A and B, respectively. CONCLUSIONS: Liposomal cisplatin in combination with paclitaxel has been shown to be much less toxic than the original cisplatin combined with paclitaxel. Nephrotoxicity in particular was negligible after liposomal cisplatin administration. TTP and survival were similar in both treatment arms.

Biweekly administration of docetaxel and gemcitabine for elderly patients with advanced non-small cell lung cancer: a phase II study.

With 69 years being the median age at diagnosis in the United States, management of elderly patients with advanced non-small cell lung cancer (NSCLC) has become a common problem faced by the oncology practitioner. We evaluated a biweekly administration of the combination regimen using docetaxel (Sanofi Aventis, Athens) and gemcitabine (Eli Lilly, Athens) in a phase II study (objective response rate, median survival, median response duration and safety). A total of 198 cycles were administered to 38 patients with advanced NSCLC with a median age of 72 years (range 65-85 years). Patients received docetaxel 80 mg/m(2 )and gemcitabine 1000 mg/m (2 )on days 1 and 14 of a 28-day cycle. Twenty patients achieved a partial response (PR) (20/34, 58.8%), 4 patients had stable disease (SD) (4/34, 11.7%) and 10 (10/34, 29.4%) had progressive disease (PD). The median time to disease progression was 3 months (range 1-11 months) with a mean survival of 7 months (range 1-29 months). Hematological and non-hematological toxic effects were generally mild to moderate and manageable: grade 3 neurotoxicity and grade 3 allergy occurred in 5 patients (13.1%) and 1 patient (2.6%), respectively. Peripheral neuropathy, mostly grades 1 and 2, was reported in 29 patients (76.3%), which was seen more frequently in patients >70 years of age (P=0.048).We conclude that the biweekly administration of a docetaxel/gemcitabine combination with G-CSF support constitutes a tolerable and convenient regimen for the treatment of elderly patients with advanced NSCLC, with efficacy similar to that reported in other regimens. Hence, this two-drug combination appears promising and warrants further evaluation.

Alternate paclitaxel-gemcitabine and paclitaxel-vinorelbine biweekly administration in non-small cell lung cancer patients: a phase II study.

BACKGROUND: In the present study, 3 cytotoxic agents were combined as front-line chemotherapy in advanced non-small cell lung cancer (NSCLC) patients. All 3 drugs have been used in other 2-agent combinations and have been shown to be effective as first-line therapy. PATIENTS AND METHODS: Sixty-one (53 male, 8 female, median age 65 years old) out of 67 patients were evaluable for response and toxicity. Eighty percent of the patients were stage IIIB and IV and 20% were inoperable stage IIIA. In order to obviate toxicity as much as possible, paclitaxel 135 mg/m2 was combined with gemcitabine 1000 mg/m2 for the first cycle, and 2 weeks later with vinorelbine 25 mg/m2, for the second cycle; this alternate schedule was repeated every 2 weeks for 9 cycles. RESULTS: No complete responses were observed; there was a 37.7% partial response rate and stable disease in 31.1% of the patients. The median survival was 13 months and 1-year survival, 53%. Myelotoxicity involved grade 3 neutropenia in 3.3% of the patients and grade 4 in 1.6%. CONCLUSION: Adverse reactions were few in this alternate administration of paclitaxel-gemcitabine and paclitaxel-vinorelbine in NSCLC patients; in more than half of the patients there was long median and 1-year survival.

Second-line chemotherapy in small cell lung cancer in a modified administration of topotecan combined with paclitaxel: a phase II study.

PURPOSE: Our main objective was to investigate the response rate in pretreated patients with small cell lung cancer (SCLC) who received a weekly administration of topotecan and paclitaxel; our secondary objectives were to assess toxicity and survival. METHODS: Topotecan 1.75 mg/m2 was combined with paclitaxel 70 mg/m2; these cytotoxic agents were administered once every week (day 1) for 3 consecutive weeks (one cycle), and repeated every 28 days (three infusions per cycle) for a minimum of three cycles. RESULTS: Forty-five patients were enrolled, 41 of whom were evaluable for response and toxicity. The median number of cycles was two (range 1-6). Eleven/forty-one (26.83%) patients responded: one complete response and ten partial responses; the median duration of response was 4 months (range 2-8 months); the median overall survival was 7 months (95% CI: 4.2-9.8). Myelotoxicity was the most common adverse reaction (grade 3 neutropenia in 19.5% of the patients and grade 4 in 7.32%). Non-hematologic toxicities varied from 2.44% to 9.76%. No patient had to stop treatment due to toxicity. CONCLUSION: Topotecan combined with paclitaxel, given on day 1 on a weekly basis, produced a response rate of 26.83% in pretreated patients with SCLC. Myelotoxicity, particularly neutropenia, was the main adverse reaction, but in a minority of patients.

Front-line paclitaxel-vinorelbine versus paclitaxel-carboplatin in patients with advanced non-small-cell lung cancer: a randomized phase III trial.

PURPOSE: This randomized phase III trial of advanced or metastatic non-small-cell lung cancer (NSCLC) was designed to compare a standard treatment such as carboplatin (CRP)-paclitaxel (PCT) with a new combination, vinorelbine (VRL)-PCT-two agents acting in microtubules. PATIENTS AND METHODS: Three hundred and sixty patients (stage IIIa, IIIb and IV) were included and evaluated for response rate, survival and toxicity. Arm A patients were treated with the control combination of CRP 6 AUC and PCT 175 mg/m(2) repeated every 3 weeks for six cycles, and arm B with the investigational combination of VRL 25 mg/m(2) and PCT 135 mg/m(2) repeated every 2 weeks for nine cycles. The patients were well balanced with respect to gender, disease stage and performance status. Arm A received 849 cycles (mean 4.59 per patient) and arm B 951 cycles (mean 5.39 per patient). RESULTS: Complete and partial response rates were 45.95% and 42.86% for arms A and B, respectively. Median survival was 11 and 10 months, 1-year survival 42.7% and 37.85% and 2-year survival 10.12% and 19% for arms A and B, respectively. Toxicity was similar in all patients, except for neutropenia, which was significantly greater in arm B. CONCLUSIONS: PCT combined with VRL produces similar (non-significant) response rates, survival and toxicity (except for neutropenia, as noted above) to standard CRP-PCT treatment in untreated advanced-stage NSCLC.

Clarithromycin reduces the severity of bronchial hyperresponsiveness in patients with asthma.

A randomised double-blind placebo-controlled study was designed to evaluate the effects of a semisynthetic macrolide antibiotic, clarithromycin, on bronchial hyperresponsiveness to methacholine in patients with a diagnosis of asthma. Adult asthma patients undergoing treatment with budesonide 400 microg b.i.d. and salbutamol 200 microg p.r.n. less than twice weekly were studied. Arm A (16 males/six females, aged 48 +/- 16 yrs) received clarithromycin 250 mg b.i.d. for 8 weeks, arm B (eight males/12 females, aged 42 +/- 12 yrs) clarithromycin 250 mg t.id. and arm C (six males/15 females, aged 41 +/- 16 yrs) placebo dextrose tablets. Bronchial hyperresponsiveness was quantified by measurement of the provocative dose of methacholine causing a 20% fall in forced expiratory volume in one second (PD20). Median (interquartile range) PD20 in the three groups before and after treatment with clarithromycin were: arm A: 0.3 (0.1-1) and 1.3 (0.6-2) mg; arm B: 0.4 (0.1-0.9) and 2 (2-2) mg; and arm C: 0.4 (0.1-0.9) and 0.3 (0.1-0.6) mg, respectively. Serum free cortisol levels were determined and remained unchanged from baseline in the clarithromycin-treated patients. It is concluded that clarithromycin reduces the degree of bronchial hyperresponsiveness in patients with asthma.