Phase II trial of oral vinorelbine in combination with cisplatin followed by consolidation therapy with oral vinorelbine in advanced NSCLC

Background: Among the cytotoxic agents commonly combined with cisplatin in the treatment of advanced NSCLC, vinorelbine has led to significant outcome improvements. Adding more than four cycles of the combination regimen increase toxicities. The availability of an oral form of vinorelbine appeared as a particularly convenient way to provide a consolidation treatment to patients who have achieved an objective response or stable disease. Patients and methods: This multi-centre phase II open-label, non-comparative study was designed to evaluate the treatment with four cycles of the combination chemotherapy with oral vinorelbine at the dose of 60 mg/m(2) on day 1 and day 8 for the first cycle and then 80mg/m(2) plus cisplatin 80mg/m(2) on day 1 every 3 weeks followed for patients with objective response or stable disease by consolidation therapy with oral vinorelbine at 80 mg/ml weekly on patients with unresectable localised or metastatic non-small-cell lung cancer (NSCLC). The primary endpoint was tumor response. The secondary objectives were progression free-survival, overall survival and toxicity assessment. Visual analogue scales (VAS) fitted by the patients were also used to evaluate subjective changes under treatment, reflecting patients' clinical benefit. Results: Fifty-six patients enrolled into the study from April 2001 to April 2002 received the combination regimen. Twenty-five patients (43.9%) also received the subsequent consolidation treatment. Partial tumor responses were obtained in 13 patients (26.5%, 95% CI 15.0-41.1) of 49 evaluable patients. Stable disease was observed in 22 (44.9%) of patients. The median duration of response was 6 months (95% Cl 4.3-8.2). The median progression free-survival was 4.2 months (95% Cl 2.8-6). The median overall survival time was 10 months (95% Cl 7.4-14) and the 1 year survival was 42.6%. The main toxicities recorded were haematological. Grade 3 and 4 neutropenia were observed in 16 patients (29.1%). Nausea, vomiting and fatigue were the major non-haematological toxicities reported. Among the symptoms recorded by the patients on VAS scales (appetite, fatigue, pain, cough, dyspnea, haemoptysis), except anorexia, all symptoms were improved during the combination therapy and in the consolidation phase. Conclusion: This study confirms that the efficacy of the cisplatin/oral vinoretbine combination in NSCLC is comparable to cisplatin/I.V. vinorelbine. This study also suggests that consolidation therapy with vinorelbine alone may probably prolong the efficacy of the combination regimen. The convenience offered to patients by an oral form of vinorelbine is a definite asset for consolidation therapy. (c) 2004 Elsevier Ireland Ltd. All rights reserved.