Sequential therapy in advanced non-small-cell lung cancer with weekly paclitaxel followed by cisplatin—gemcitabine—vinorelbine. A phase II study

Summary Objectives: New effective therapies are needed to improve the outcome of patients with advanced non-small-cell lung cancer (NSCLC). The aim of this study was to assess the response rate and survival obtained with a sequential regimen of chemotherapy. Patients and methods: Patients with newly diagnosed stage IIIb—IV NSCLC were included. They all had measurable disease and a good performance status (0–2 in the Eastern Cooperative Oncology Group scale). Chemotherapy consisted of weekly paclitaxel 150 mg/m2 × 6, followed two weeks later by cisplatin 100 mg/m2 on day 1, gemcitabine 1000 mg/m2 on days 1 and 14, and vinorelbine 25 mg/m2 on days 1 and 14 (CGV). CGV was administered every 28 days for a maximum of six courses. Results: Fifty-two patients were included, 19 (37%) with stage IIIb and 33 (63%) with stage IV disease. After therapy with weekly paclitaxel, 29 partial responses were obtained (56%, 95% confidence interval (95% CI): 38%–67%), whereas 15 patients had stable disease (29%) and eight had a progression (15%). After CGV, there were four complete remissions (8%) and 24 partial responses (46%), for an overall response rate of 54% (95% CI: 37%–65%). Eight patients had stable disease (15%) and 16 had a progression (31%). No patient progressing after paclitaxel responded to CGV, whereas 5 out of 15 patients with stable disease reached a partial response with CGV (33%). On the contrary, 5 out of 29 patients with a partial response to paclitaxel progressed after CGV (17%). Median survival has not been reached after a median followup of 14 months. Median time to progression was nine months. Fifty-six percent of patients remain alive at one year. Two hundred eighty-nine courses of paclitaxel and 170 of CGV were given, with a median of 5.5 and 3.4 per patient, respectively (ranges 2–6 and 0–6. respectively). WHO grade 3–4 toxicities for paclitaxel were: neutropenia in two patients (4%) and peripheral neuropathy in five (10%). Two patients had allergic reactions requiring paclitaxel withdrawal, whereas four (8%) had hyperglycemia > 250 mg/ml. Grade 3–4 toxicities for CGV were: neutropenia in ten patients (20%), peripheral neuropathy in six (12%), anemia in four (8%), nausea/vomiting in five (10%). thrombocytopenia in two (4%), and fatigue in four (8%). Conclusion: Our results suggest that sequential chemotherapy with weekly paclitaxel followed by CGV is highly active in patients with advanced NSCLC and has an acceptable toxicity. This schedule deserve