Bleomycin, methotrexate, and CCNU in locally advanced or recurrent, inoperable, squamous-cell carcinoma of the vulva: An EORTC Gynaecological Cancer Cooperative Group study

Objectives. To investigate tumor response rate and treatment toxicity of a modified combination chemotherapy consisting of bleomycin (B), methotrexate (M), and CCNU (C) for patients with locally advanced, squamous-cell carcin oma of the vulva (not amenable to resection by standard radical vulvectomy) or recurrent disease (after incomplete resection). Tumor resectability was reassessed in patients who had responded to chemotherapy. Methods. The regimen consisted of bleomycin 5 mg intramuscular (im) days 1- 5, CCNU 40 mg per os (po) days 5-7, and methotrexate 15 mg po days 1 and 4 during the first week. During weeks 2-6 the patient was administered bleomy cin 5 mg im days 1 and 4, and methotrexate 15 mg po on day 1 of the week. T his 6-week cycle was repeated at 49-day intervals. Results. Twenty-five eligible patients with a median age of 66 years (range , 39-82 years) were entered in this phase II trial. Twelve patients had pri mary locally advanced disease, 13 patients had a locoregional recurrence, a nd all received up to three BMC cycles. Two complete and twelve partial res ponses were observed (response rate, 56%; 95% confidence limits, 35-76%). T he BMC regimen was associated with major hematological side effects and mil d signs of bleomycin-related pulmonary toxicity. At a median follow-up of 8 months, 3 patients were alive, 18 had died due to malignant disease, 2 had died due to toxicity, and 2 had died due to intercurrent disease and unkno wn cause. The median progression-free survival was 4.8 months and the media n survival was 7.8 months. The 1-year survival was 32% (95% confidence limi ts, 13-51%). Conclusion. The present data confirm the therapeutic activity of the BMC re gimen in locoregionally advanced or recurrent squamous-cell carcinoma of th e vulva. Following neoadjuvant chemotherapy, the overall response rate was 56%. BMC is an outpatient treatment that may play a role in the palliative therapy of advanced or recurrent vulva cancer. (C) 2001 Academic Press.