MITOMYCIN-C, VINBLASTINE, AND CARBOPLATIN REGIMEN IN PATIENTS WITH NONSMALL CELL LUNG-CANCER - A PHASE-II TRIAL

BACKGROUND. The mitomycin C, vinblastine, and cisplatin (MVP) combinat ion is one of the most frequently used in the palliative setting, but it produces considerable toxicity. Carboplatin and cisplatin have diff erent patterns of toxicity. The goal of this study was to evaluate a c ombination similar to MVP, using carboplatin instead of cisplatin to r ender it more feasible in an outpatient setting. METHODS. Inclusion cr iteria for this study included: inoperable patients or patients relaps ing after previous surgery, with nonsmall cell lung carcinoma (NSCLC), a performance status CPS) >50%, and no previous chemotherapy. The che motherapy regimen included carboplatin, 300 mg/m(2) on Day 1; mitomyci n, 8 mg/m(2) on Day 1; and vinblastine, 4 mg/m(2) on Days 1, 8, and 15 (on Day 15 vinblastine was delivered only in the first cycle) (MVC) e very 3 weeks for at least 3 cycles. RESULTS. From August 1991 until Au gust 1994, 70 patients entered the trial. All were evaluable for toxic ity and response. The median age was 62 years (range, 40-73 years). Th e male/female ratio was 60:10 (86%:14%); the ratio of Stage III to Sta ge IV disease was 26:44 (37%:63%); and the ratio of PS > 70 to less th an or equal to 70 was 49:21. A total of 296 cycles (median, 4 [range, 1-6 cycles] per patient) were delivered, 280 of 296 (95%) in an outpat ient setting with only 4 patients requiring hospitalization for treatm ent delivery. Overall response rate (RR) was 38.6% (95% confidence int erval [CI], 27-51%) (1 complete response, 1.5%; 26 partial responses, 37.1%). Median duration of response was 9.8 months (range, 2-27 months ). In Stage III patients the RR was 42% and in Stage IV patients it wa s 34%. Overall median survival was 9.5 months (95% CI, 6.8-15.3 months ). Survival at 1 year was 39% (standard error [SE] 3.6%) and was 11% a t 2 years (SE 3.6%). In Stage III patients median survival was 13 mont hs and the 1-year survival rate was 54% (SE 10%); Stage IV patients ha d a median survival of 7.4 months and a 1-year survival rate of 28% (S E 7%). Delivered dose intensity was: carboplatin, 71%; vinblastine, 60 %; and mitomycin C, 77% of the planned dose intensity. The back calcul ation of carboplatin area under the curve (AUC) with Calvert's formula and with the Cockcroft-Gault glomerular filtration rate estimation, s howed a median AUC value of 4 (range, 2-8). Using the more precise Cha telut formula, AUC was again 4 (range, 2-7). Hematologic toxicity was the major side effect; Grades 3 and 4 leukopenia were observed in 34% and 6% of patients, respectively, and Grades 3 and 4 thrombocytopenia in 25% and 4% of patients, respectively. Grade 2 infection occurred in 10% of patients, with only 1 case of sepsis; severe constipation and Grade 2 alopecia occurred in only 1 patient; and no case of higher tha n Grade 1 nephrotoxicity was observed. No pulmonary toxicity was obser ved. Compliance with treat ment was good with only one patient refusal after the first cycle. CONCLUSIONS. Chemotherapy for advanced NSCLS i s still controversial, because effectiveness in terms of RR and sympto m control must be weighed against treatment toxicity and costs. From o ur study it appears that MVC is easy to deliver in an outpatient setti ng, and has good patient compliance, low toxicity profile, and promisi ng RR and response duration. The substitution of carboplatin for cispl atin in regimens for advanced NSCLC should be considered. (C) 1996 Ame rican Cancer Society.