Sequential administration of vinorelbine plus cisplatin and bevacizumab followed by docetaxel plus gemcitabine and bevacizumab compared to docetaxel plus cisplatin and bevacizumab regimen as first-line therapy for advanced or metastatic non-squamous non-small cell lung cancer: A multicenter randomized phase II trial of the Hellenic Oncology Research Group (HORG).

OBJECTIVES: To compare the activity and tolerance of the consecutive administration of four active chemotherapeutic agents in combination with bevacizumab to a bevacizumab- and platinum-based chemotherapy doublet as front-line treatment in patients with non-squamous NSCLC. PATIENTS AND METHODS: Patients with advanced/metastatic NSCLC, performance status of 0-2 and normal organ function were randomized to receive either 3 cycles every 3 weeks of cisplatin 80 mg/m(2) (day 1), oral vinorelbine 60 mg/m(2) (days 1 and 8) and bevacizumab 15 mg/kg (day 1) every 3 weeks (VCB regimen) followed by 3 cycles of docetaxel (75 mg/m(2), day 1), gemcitabine (1100 mg/m(2), days 1 and 8) and bevacizumab 15 mg/kg (day 1) (DGB regimen) (arm A) or 6 cycles of cisplatin 80 mg/m(2), docetaxel 75 mg/m(2) and bevacizumab 15 mg/kg on day 1 (DCB regimen; arm B) every 3 weeks. RESULTS: Thirty-eight and 39 patients were enrolled in arm A and B, respectively. The study did not meet its primary endpoint since, the ORR was 39.5% (95% CI: 23.9-55.0%; 1CR and 14 PR) and 46.2% (95% CI: 30.5-61.8%; 2 CR and 16 PR) in arm A and B, respectively (p=0.554). There was no significant difference in terms of response duration (7.4 versus 4.7 months in arm A and B, respectively; p=0.697), progression-free survival (5.8 versus 5.5 months, respectively; p=0.540) and overall survival (16.9 versus 10.9 months; p=0.390). No difference was recorded between the two arms regarding the toxicity profile. There were two drug-related deaths in arm B. CONCLUSION: Sequential therapy of VCB followed by DGB is a feasible and well-tolerated regimen but failed to show any superiority over the standard DCB regimen.

A phase I clinical trial of weekly oral topotecan for relapsed small cell lung cancer.

PURPOSE: To determine the dose-limiting toxicities (DLTs) and the maximum tolerated dose (MTD) of oral topotecan administered weekly in patients with relapsed small cell lung cancer (SCLC). PATIENTS AND METHODS: Patients were treated with oral topotecan on days 1, 8, and 15, every 28 days. The dose was escalated by 0.5 mg/m² increments from the starting dose of 3 mg/m² until the MTD was reached. DLTs were defined as grade 4 neutropenia, febrile neutropenia, grade 4 thrombocytopenia, non-hematologic toxicity ≥grade 3, any toxicity precluding the treatment on days 8 or 15 of the first cycle, or delay of the second cycle for more than 7 days. RESULTS: Eighteen patients were enrolled. Thirteen patients received oral topotecan as second-line and five as third- or further-line treatment. The DLT level was reached at 4.5 mg/m², and the MTD was determined to be 4 mg/m². DLTs consisted of grade 2/3 neutropenia and grade 2 thrombocytopenia precluding treatment on day 15 of the first cycle or on day 1 of the second cycle. The most frequent toxicities were grade 2-3 neutropenia (27.8 % of patients), grade 2-3 anemia (33.3 %), grade 2 thrombocytopenia (16.7 %), and grade 2-3 fatigue (44.4 %). The response rate was 11.1 %, the median progression-free survival 2.3 months, and the median overall survival 5.1 months. CONCLUSION: The recommended phase II dose of weekly oral topotecan in pretreated patients with SCLC is 4 mg/m² on days 1, 8, and 15 every 28 days.

Vinorelbine and cisplatin combination in pretreated patients with advanced non-small cell lung cancer pretreated with a taxane-based regimen: a multicenter phase II study.

PURPOSE: To assess the efficacy and tolerance of the vinorelbine/cisplatin combination in non-small cell lung cancer patients pre-treated with a taxane-based regimen. PATIENTS AND METHODS: Among the 32 enrolled patients, 28 (87.5%) had a PS (WHO) of 0-1 and 13 (40.6%) have previously received both platinum compounds and taxanes. Vinorelbine (25 mg/m2 on days 1 and 8) was given by a rapid i.v. infusion and cisplatin (80 mg/m2 on day 8) after appropriate hydration. The treatment was repeated every 3 weeks. RESULTS: A partial response was achieved in six patients (ORR=18.8%; 95% confidence interval: 5.23-32.27); 13 (44.8%) and 10 (34.5%) patients had stable and progressive disease, respectively (intention-to-treat analysis). Four partial responses were observed in patients who were previously treated with taxanes/platinum-containing regimens. The median time to tumor progression was 4.7 months (range, 1.3-15.4). After a median follow-up period of 6.3 months (range, 1.3-15.4) the median overall survival was 7.6 months and the 1-year survival rate 17.7%. Grade 3 and 4 granulocytopenia was observed in 11 (34.4%) patients and grade 4 thrombocytopenia in one (3.1%). Eleven (34.4%) patients presented grade 2 and 3 anemia. Febrile neutropenia occurred in one (3.1%) patient. Grade 3 and 4 nausea/vomiting was reported in one (9.3%) patient each and grade 2 fatigue in four (12.5%). CONCLUSIONS: The combination of vinorelbine and cisplatin is an active and well tolerated salvage regimen in NSCLC patients pre-treated with taxane-based chemotherapy.