Randomized study of maintenance vinorelbine in responders with advanced non-small-cell lung cancer.
BACKGROUND
Prolongation of chemotherapy duration, usually referred to as maintenance chemotherapy, has been considered as an approach to improve survival of patients with advanced non-small-cell lung cancer (NSCLC). If the maintenance regimen differs from the induction regimen, patients will receive not only higher total doses of chemotherapy but also earlier delivery of non-cross-resistant agents. We conducted a randomized trial to compare maintenance vinorelbine therapy with observation in previously untreated patients who responded to induction treatment with mitomycin-ifosfamide-cisplatin (MIC).


METHODS
Patients with stage IIIB NSCLC were treated with two monthly MIC cycles followed by radiotherapy; those with "wet" stage IIIB (pleural or pericardial involvement), with stage IIIB with supraclavicular node involvement, or stage IV (i.e., metastatic) NSCLC were treated with four monthly MIC cycles. Patients who responded to induction treatment were randomly assigned to receive intravenous vinorelbine at a dose of 25 mg x m(-2) x wk(-1) for 6 months or no further treatment. Survival comparisons used the log-rank test and the Cox regression adjusted for stage. All statistical tests were two-sided.


RESULTS
A total of 573 patients were registered, of whom 227 responded to induction treatment and 181 were randomly assigned (91 to maintenance vinorelbine and 90 to observation) between January 1994 and March 2000. One- and 2-year survival rates were 42.2% and 20.1% in the vinorelbine arm and 50.6% and 20.2% in the observation arm, respectively (log-rank P = .48). The hazard ratio of survival after adjustment on stage, in the vinorelbine arm relative to the observation arm, was 1.08 (95% confidence interval = 0.79 to 1.47; P = .65). There was also no difference between arms in progression-free survival (log-rank P = .32).


CONCLUSIONS
Maintenance vinorelbine did not improve survival of patients with advanced NSCLC who responded to induction MIC treatment. Nevertheless, other agents, including docetaxel and targeted agents, should be evaluated as maintenance agents before the concept is abandoned.
Westeel
Virginie
V
Chest Disease Department, Jean Minjoz University Hospital, Besançon, France.
Quoix
Elisabeth
E
Moro-Sibilot
Denis
D
Mercier
Mariette
M
Breton
Jean-Luc
JL
Debieuvre
Didier
D
Richard
Philippe
P
Haller
Mary-Anne
MA
Milleron
Bernard
B
Herman
Dominique
D
Level
Marie-Claude
MC
Lebas
François-Xavier
FX
Puyraveau
Marc
M
Depierre
Alain
A
D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016685:Mitomycin / Q000008:administration & dosage; D009367:Neoplasm Staging; D016017:Odds Ratio; D016016:Proportional Hazards Models; D012074:Remission Induction; D016019:Survival Analysis; D017211:Treatment Failure; D016896:Treatment Outcome; D014747:Vinblastine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D000077235:Vinorelbine
D000972:Antineoplastic Agents, Phytogenic; D016685:Mitomycin; D014747:Vinblastine; D002945:Cisplatin; D000077235:Vinorelbine; D007069:Ifosfamide