A four-drug combination chemotherapy with cisplatin, mitomycin, vindesine and 5 fluorouracile: a regimen associated with major toxicity in patients with advanced non-small cell lung cancer.
The purpose of this study was to determine the activity of a 4-drug combination chemotherapy: cisplatin, mitomycin C, vindesine and 5-fluorouracil (5-FU) in patients with advanced non-small cell lung cancer (NSCLC). Chemotherapy consisted of the administration of cisplatin (30 mg/m2 d 1-4), mitomycin C (10 mg/m2 d 1), vindesine (3 mg/m2 d 1) and 5-FU (1 g/m2 d 1-4 by continuous intravenous infusion). In patients older than 70 years, and in those who received prior irradiation or chemotherapy, cisplatin and 5-FU were omitted on day 4. Courses were repeated every 4 weeks and evaluation of response was performed after the first 2 courses. In case of response, treatment was continued until best response or untolerable toxicity. Among 182 eligible patients, 75% had received no prior therapy; 41% had locoregional disease and 59% metastatic disease; 41% lost more than 5% of their pretherapy body weight. A 34% objective response rate was observed in the 164 evaluable patients (31% in all the eligible patients) including 4 complete and 52 partial responses. Patients with locoregional disease had a significantly better response rate than those with metastases (44% vs 27%). The overall median survival was 26 weeks. Significant hematological toxicity was documented but the most serious adverse event was the occurrence of 18 (10%) cardiac or sudden deaths. These toxic deaths were significantly associated with a 5% loss of body weight prior to therapy. The addition of 5-FU to combination of cisplatin, mitomycin C and vindesine does not improve antitumoral effect but results in very significant cardiac toxicity.
Klastersky
J
J
Service de Médecine, Institut Jules Bordet, Brussels, Belgium.
Sculier
J P
JP
Ries
F
F
Dabouis
G
G
Libert
P
P
Schmerber
J
J
Thiriaux
J
J
Berchier
M C
MC
Bureau
G
G
Van Cutsem
O
O
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality; D002945:Cisplatin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D008937:Mitomycins / Q000008:administration & dosage; D011379:Prognosis; D016019:Survival Analysis; D014751:Vindesine / Q000008:administration & dosage
D008937:Mitomycins; D002945:Cisplatin; D014751:Vindesine; D005472:Fluorouracil