Randomized Trial With Vinorelbine and Gemcitabine Versus Docetaxel and Gemcitabine in Patients With Non-Small Cell Lung Cancer

Vinorelbine and Gemcitabine Versus Docetaxel and Gemcitabine as First Line Treatment in Patients With Advanced or Metastatic Non Small Cell Lung Cancer (NSCLC). A Prospective , Multicenter, Randomized, Phase III Trial

The purpose of this study is to evaluate whether the gemcitabine/vinorelbine combination versus the gemcitabine/docetaxel combination as first line treatment, offers a survival advantage in patients with locally advanced/metastatic NSCLC.

Cisplatin-based chemotherapy represented the backbone of treatment of advanced NSCLC. However, several trials comparing platinum versus non-platinum based chemotherapy regimens failed to demonstrate a statistically significant difference in terms of time to tumor progression or survival. Newer agents such as gemcitabine, docetaxel and vinorelbine have shown significant activity in the treatment of NSCLC. Gemcitabine/vinorelbine combination as first line treatment has demonstrated a response rate (RR) of 18-43% and a median overall survival (OS) of 9.8-13 months. Similarly, the gemcitabine/docetaxel combination has shown a RR 32-35% and a median OS of 9-12 months. Given their proven efficacy, the combination of these two doublets, would be interesting.

Inclusion Criteria:

• Histologically or cytologically confirmed, unresectable locally advanced (stage IIIB with pleural effusion) and/or metastatic (stage IV) NSCLC
• No previous therapy for advanced/metastatic NSCLC is allowed
• Age > 18 years
• Bidimensionally measurable disease
• Performance status (WHO) 0-2
• Adequate liver (serum bilirubin < 1.5 times the upper normal limit (UNL); AST and ALT < 2.5 times the UNL in the absence of demonstrable liver metastases, or < 5 times the UNL in the presence of liver metastases); adequate renal function (serum creatinine < 1.5 times the UNL); and bone marrow (neutrophils ≥ 1.5x 109 /L, and platelets ≥ 100x 109 /L) function
• Previous radiotherapy, either in the adjuvant setting or for the treatment of metastatic disease is allowed provided that the measurable lesions are outside the radiation fields
• Life expectancy of more than 3 months
• Patient able to take oral medication
• At least 4 weeks since prior radiotherapy
• Written informed consent

Exclusion Criteria:

• Active infection
• History of significant cardiac disease (unstable angina, congestive heart failure, myocardial infarction within the previous 6 months, ventricular arrhythmias)
• Malnutrition (loss of ≥ 20% of the original body weight)
• Performance status: 3-4
• Sensor or motor neuropathy > grade I
• Second primary malignancy, except for non-melanoma skin cancer
• Psychiatric illness or social situation that would preclude study compliance
• Pregnant or lactating women
• Known, symptomatic central nervous system metastases