Vinorelbine Plus Cisplatin Versus Docetaxel Plus Gemcitabine in Advanced Non-Small-Cell Lung Cancer: A Phase III Randomized Trial

Abstract

PURPOSE To compare the activity and tolerability of docetaxel/gemcitabine (DG) and vinorelbine/cisplatin (VC) combinations in chemotherapy-naive non-small-cell lung cancer (NSCLC) patients. PATIENTS AND METHODS Patients with advanced NSCLC were randomly assigned to receive either DG (gemcitabine 1,000 mg/m(2) [days 1 and 8] plus docetaxel 100 mg/m(2) [day 8]) or VC (vinorelbine 30 mg/m(2) [days 1 and 8] plus cisplatin 80 mg/m(2) [day 8]) and prophylactic recombinant human granulocyte colony-stimulating factor (150 microg/m(2) subcutaneously [day 9 through 15]) every 3 weeks. Results A total of 413 randomly assigned patients were analyzed for response and toxicity (DG, n = 197; VC, n = 192). Median survival was 9.0 and 9.7 months (P = .965) for DG and VC arms, respectively; the corresponding 1-year survival rates were 34.3% and 40.8%, respectively. Overall response rate was 30% (95% CI, 23.9% to 36.3%) and 39.2% (95% CI, 32.5% to 45.9%; P = .053) for DG and VC, respectively. Toxicity was as follows (DG v VC): grade 2 to 4 anemia, 34% v 55% (P = .0001); grade 3 to 4 neutropenia, 16% v 37% (P = .0001); febrile neutropenia, 6% v 11% (P = .009); and grade 3 to 4 nausea and vomiting, 1% v 15% (P = .003). Nephrotoxicity occurred in 8% and ototoxicity in 2% of VC-treated patients. There were five and six treatment-related deaths in the DG and VC arms, respectively. Quality of life was improved in DG but not in VC patients. CONCLUSION Although the two regimens produced comparable overall survival, the DG regimen had a better toxicity profile. Therefore, DG could be used in the first-line setting of advanced NSCLC, especially for patients who cannot tolerate cisplatin.

Vinorelbine/carboplatin vs gemcitabine/carboplatin in advanced NSCLC shows similar efficacy, but different impact of toxicity

“…For vinorelbine/platinum combinations, recent phase III studies have yielded median survival data ranging from 6.5 to 11 months (Wozniak et al, 1998;Kelly et al, 2001;Scagliotti et al, 2002;Fossella et al, 2003;Gebbia et al, 2003;Georgoulias et al, 2005;Martoni et al, 2005;Tan et al, 2005;Plessen et al, 2006). In the gemcitabine/platinum metaanalysis (Le Chevalier et al, 2005), median survival in the gemcitabine group was 9 months, reflecting the mean value for a number of studies (Le Chevalier et al, 1994;Cardenal et al, 1999;Sandler et al, 2000;Scagliotti et al, 2002;Schiller et al, 2002;Alberola et al, 2003;Gebbia et al, 2003;Smit et al, 2003;Zatloukal et al, 2003;Martoni et al, 2005;Rudd et al, 2005;Sederholm et al, 2005).…”

A multicenter phase I trial of metronomic oral vinorelbine plus cisplatin in patients with NSCLC

“…The cisplatin/vinorelbine doublet is a well studied and active doublet in the treatment of NSCLC either in the adjuvant [27,28] or in the advanced disease setting [29][30][31]. On the other hand, this combination is very toxic with severe neutropenia occurring in more than 40%-80% of the patients [27,29,31].…”

Impact of Third-Generation Drugs on the Activity of First-Line Chemotherapy in Advanced Non-Small Cell Lung Cancer: A Meta-Analytical Approach

“…Reasons for exclusion were not stated in eight studies [30,31,40,42,43,48,57,64], whereas we were unable to assess if any exclusion criteria were applied in a trial published in Chinese only [46]. Response was assessed according to the World Health Organization standard criteria [72] in 19 trials [22,23,25,29,32,34,35,39,44,45,47,49,50,52,53,59,62,65,68], according to the Southwest Oncology Group guidelines [73] in two studies [21,24], and according to the Response Evaluation Criteria in Solid Tumors [74] in four trials [60,61,66,67].…”