Cisplatin-vindesine-mitomycin (MVP) vs cisplatin-ifosfamide-vinorelbine (PIN) vs carboplatin-vinorelbine (CaN) in patients with advanced non-small-cell lung cancer (NSCLC): a FONICAP randomized phase II study

Abstract

Summary In the present multicentre randomized phase 11 trial, the activity and toxicity of three platinum-based combination regimens for the treatment of advanced non-small-cell lung cancer (NSCLC) were evaluated. The three regimens were: MVP (mitomycin-C 6 mg m-2 on day 1, vindesine 3 mg m-2 on days 1 and 15, and cisplatin 80 mg m-2 on day 1 every 28 days), PIN (cisplatin 80 mg m-2 day 1, ifosfamide 3 g m-2 day 1 and vinorelbine 25 mg m-2 day 1 and 8 every 21 days) and CaN (carboplatin 350 mg m-2 day 1 and vinorelbine 25 mg m-2 days 1 and 8 every 28 days). A total of 140 chemotherapy-naive patients entered the study; 49 patients were treated with MVP, 48 with PIN and 43 with CaN. Sixty-seven per cent of the patients had stage IV disease. Response rates, calculated on an 'intention to treat' basis, were as follows: MVP, 14.3% (95% Cl 5.94-27.2%); PIN, 16.7% (95% Cl 7.4-30.2%); and CaN, 14% (95% Cl 5.3-27.9%). The overall median survivals were 256, 269 and 243 days for patients treated with MVP, PIN and CaN respectively. Myelosuppression was the most frequent toxicity: grade 3-4 leucopenia was observed in 14.3%, 25% and 18.6% of patients treated with MVP, PIN and CaN respectively. This multicentre phase 11 randomized trial shows that MVP, PIN and CaN can be administered on an outpatient basis with acceptable toxicities. Unfortunately, the three regimens showed an activity significantly lower than that reported in previous single-institution phase 11 trials.

A meta-analysis of randomized controlled trials comparing carboplatin-based to cisplatin-based chemotherapy in advanced non-small cell lung cancer

“…Six publications were excluded for following reasons: preliminary reports [31] in Jelic trial [15]; interim analysis [32] in Fossella's trial [20]; inappropriate randomization [33]; comparison of single platinum-based regimen to doublet regimen [34]; enrolling previously treated patients [35], and the protocol registering and newly verifying in December 2006 in PDQ database [36]. Thus, 18 trials involving 6906 patients with advanced NSCLC were ultimately analyzed [10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27].…”

“…Eighteen randomized trials meeting the inclusion criteria were identified, among them, five trials were phase II RCTs [11][12][13]21,27], the others were phase III RCTs. There was no placebo-controlled double-blinded trial.…”

“…Although many randomized controlled trials were performed to compare carboplatin-based to cisplatin-based chemotherapy, the results were inconsistent [10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27]. In 2004, Hotta et al performed a meta-analysis of eight randomized controlled trials, which indicated that cisplatin produced a higher response rate; however, the survival advantage was not significant.…”

Ifosfamide in Non-Small Cell Lung Cancer

“…At the University of Pisa, a regimen consisting of vinorelbine 25 mg/m 2 on days 1 and 8, ifosfamide 3 g/m 2 on day 1 and cisplatin 80 mg/m 2 on day 1, every 3 weeks, was administered to 76 patients. A noteworthy response rate of 51% was reported, with 1-year survival of 43% [27]; unfortunately a subsequent randomized phase II multicenter trial found, with the same combination, an overall response rate of 16.7% in 48 patients [28]. Souquet et al [29]conducted a randomized phase II trial with cisplatin 75 mg/m 2 on day 1, ifosfamide 3 g/m 2 on day 1 and increasing doses of vinorelbine in three groups of patients.…”

A 53-Year-Old Patient with Unilateral Pulmonary Infiltrates following a Single Dose of Mitomycin, Vindesine and Cisplatin Chemotherapy for Non-Small-Cell Lung Cancer

“…The clinical course of this patient with squamous cell lung cancer metastasizing to hilar and retroperitoneal lymph nodes and both kidneys was characterized by a rapid clinical deterioration with increasing dyspnea as well as unilateral pulmonary infiltrates less than 2 days after the administration of the first dose of mitomycin, vindesine and cisplatin according to established treatment guidelines [12][13][14][15].…”