Randomized phase III trial of bleomycin, vindesine, mitomycin-C, and cisplatin (BEMP) versus cisplatin (P) in disseminated squamous-cell carcinoma ofthe uterine cervix: An EORTC Gynecological Cancer Cooperative Group study

Purpose: Three previous mitomycin-cisplatin-based chemotherapy trials condu cted within the EORTC Gynecological Cancer Cooperative Group (GCCG) in pati ents with disseminated squamous-cell carcinoma of the uterine cervix (SCCUC ) suggested that with such regimens a higher overall response rate and a hi gher complete response rate could be obtained compared to what might have b een expected from cisplatin alone. In that respect the combination of bleom ycin, vindesine (Eldesine(R)), mitomycin C and cisplatin (BEMP) was the mos t promising. In the present study BEMP has been compared with the best sing le agent, cisplatin (P) in the expectation that improved response rates mig ht translate into a better survival. Patients and methods: Eligible patients were those with SCCUC and dissemina ted measurable disease outside previously irradiated areas, aged less than or equal to 75 years, with a WHO performance status less than or equal to2 and adequate bone marrow, renal, hepatic and pulmonary function, who gave c onsent according to regulations followed in individual institutions. Patien ts were randomized to BEMP: E 3 mg/m(2) day 1, P 50 mg/m(2) day 1, B 15 mg (24-hour infusion) day 2-4 and M 8 mg/m(2) (at alternate cycles), or P 50 m g/m(2). The first four cycles were given every 3 weeks (induction phase). S ubsequent cycles were given every four weeks (maintenance phase), during wh ich B was deleted from BEMP (MEP). Patients failing on P could be treated w ith BEM. Of the 287 patients entered, 235 were eligible and 201 evaluable f or response. Results: BEMP induced a significantly higher response rate than P (42% vs. 25%, P = 0.006). There was no difference in complete response rate (11% vs. 7%). BEMP was significantly more toxic than P (+/-BEM), both with respect to hematologic and nonhematologic toxicities. After a median follow-up of 6 .1 years, survival curves were not significantly different. Median progress ion-free survival and overall survival were 5.3 and 10.1 months with BEMP a nd 4.5 and 9.3 months with P (+/-BEM), respectively. In a multivariate anal ysis of prognostic factors for survival, a lower age (P = 0.003), a lower p erformance status (P = 0.0001) and a short (<1 year) interval since diagnos is (P = 0.0152) were all associated with an increased risk of dying. For pr ogression-free survival, lower age, prior radiotherapy, locoregional involv ement and no prior surgery were associated with a high risk. Treatment with BEMP or P had no significant impact on survival, but for progression-free survival there was a trend in favor of BEMP (P = 0.0893). Adjusting for pro gnostic factors did not change the effect of treatment. Conclusions: Combination chemotherapy with BEMP produces more toxicity and more responses compared with cisplatin alone in patients with disseminated SCCUC, but this does not translate into a better survival. Therefore, in th e palliative setting single-agent cisplatin should remain the standard ther apy for these patients.