Vinorelbine plus cisplatin versus cisplatin plus vindesine and mitomycin C in stage IIIB-IV non-small cell lung carcinoma: a prospective randomized study.
OBJECTIVE
To compare a regimen of vinorelbine and cisplatin (VC) to the combination of mitomycin, vindesine, and cisplatin (MVP) in patients with stage IIIB or stage IV non-small cell lung cancer (NSCLC). The main endpoits were analysis of objective response rates, toxicity, time to progression, and overall survival.


METHODS
247 eligible patients were randomized to receive (a) vinorelbine 25 mg/m(2) intravenous bolus on days 1 and 8 plus cisplatin 100 mg/m(2) on day 1 every 4 weeks, or (b) mitomycin c 8 mg/m(2) i.v. on day 1, vindesine 3 mg/m(2) i.v. on days 1, 8, 15 and 22, plus cisplatin 100 mg/m(2) on day 1 every 4 weeks. In subsequent cycles vindesine was given every other week. For both treatments a maximum of six cycles was planned. Patients with performance status 0-2 according to the ECOG scale were enrolled. Response and toxicity were evaluated according to the WHO criteria. Analysis of clinical efficacy was performed according to an intent-to-treat analysis.


RESULTS
No statistically significant differences in clinical efficacy were observed between the two chemotherapy regimens. The overall objective response rates were 39% (95% CL, 31-49%) in the VC arm and 42% (95% CL, 33-51%) in the MVP arm (P=0.13). Median time to progression was 4.2 and 4.5 months for the MVP arm and the VC arm, respectively. Median overall survival was 7 months in the VC arm and 8 months in the MVP one (log-rank test, P=0.898). These differences were not statistically significant. However, leukopenia and thrombocytopenia were significantly higher in the MVP arm than in the VC (P=0.0001; P=0.0002). Grade 3 alopecia was more frequent in the MVP arm than in the VC one (P<0.001), which was associated with higher rate of phlebitis (P=0.037).


CONCLUSIONS
Data achieved in this study suggest that the vinorelbine-cisplatin doublet is similar to the three-drug MVP regimen in term of overall response rate, time to progressive disease, and overall survival. However, hematological toxicity and alopecia are more frequent and severe in the MVP regimen which therefore appears to be less tolerable than the VC regimen. The combination of vinorelbine and cisplatin may be considered as a reference treatment for future studies on the treatment of advanced NSCLC.
Istituto Clinica Medica, University of Palermo, Palermo, Italy. vittorio.gebbia@tin.it
Vittorio
V
Gebbia
Domenico
D
Galetta
Fernando
F
Riccardi
Cesare
C
Gridelli
Ernesto
E
Durini
Nicolò
N
Borsellino
Nicolò
N
Gebbia
Matteo
M
Valdesi
Michele
M
Caruso
Roberto
R
Valenza
Giuseppe
G
Pezzella
Giuseppe
G
Colucci
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage / Q000627:therapeutic use*; D018450:Disease Progression; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016685:Mitomycin / Q000627:therapeutic use*; D009367:Neoplasm Staging; D011446:Prospective Studies; D015996:Survival Rate; D016896:Treatment Outcome; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D014751:Vindesine / Q000627:therapeutic use*; D000077235:Vinorelbine
D016685:Mitomycin; D014747:Vinblastine; D002945:Cisplatin; D000077235:Vinorelbine; D014751:Vindesine