Bleomycin, Methotrexate, and CCNU in Locally Advanced or Recurrent, Inoperable, Squamous-Cell Carcinoma of the Vulva: An EORTC Gynaecological Cancer Cooperative Group Study 1 H. C. Wagenaar, M.D.,* , ² N. Colombo, M.D.,‡ ,2 I. Vergote, M.D.,§ G. Hoctin-Boes, M.D., M.Sc.,² G. Zanetta, M.D., ¶ S. Pecorelli, M.D., A. J. Lacave, M.D.,** Q. van Hoesel, M.D.,²² A. Cervantes, M.D.,‡‡ G. Bolis, M.D.,§§ M. Namer, M.D., ¶¶ C. Lhomme ´, M.D., J. P. Guastalla, M.D.,*** M. A. Nooij, M.D.,²²² A. Poveda, M.D.,‡‡‡ V. Scotto di Palumbo, M.D.,§§§ and J. B. Vermorken, M.D. ¶¶¶ *Department of Gynaecology, Leiden University Medical Center, Leiden, The Netherlands; ² EORTC Data Center, Avenue E. Mounier 83-bte 11, 1200 Brussels, Belgium; ‡Division of Gynecology, European Institute of Oncology, Milan, Italy; §Department of Gynaecologic Oncology, University Hospital Leuven, Leuven, Belgium; ¶ Department of Gynaecology, Ospedale San Gerardo, Monza, Italy; Department of Gynaecology, Universita di Brescia, Brescia, Italy; **Department of Medical Oncology, Hospital General de Asturias, Oviedo, Spain; ²² Department of Medical Oncology, St. Radboud University Hospital, Nijmegen, The Netherlands; ‡‡Department of Medical Oncology, Hospital Clinico Universitario de Valencia, Valencia, Spain; §§Department of Oncology, Instituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy; ¶¶ Department of Oncology, Centre Antoine Lacassagne, Nice, France; Department of Gynaecology, Institut Gustave Roussy, Villejuif, France; ***Department of Oncology, Centre Le ´on Be ´rard, Lyon, France; ²²² Department of Clinical Oncology, Leiden University Medical Center, Leiden, The Netherlands; ‡‡‡Department of Oncology, Instituto Valenciano de Oncologia, Valencia, Spain; §§§Department of Gynaecology, Ospedale Generale Provinciale San Camillo de Lellis, Rieti, Italy; and ¶¶¶ Department of Oncology, University Hospital Antwerp, Edegem, Belgium Received March 1, 2001; published online April 24, 2001 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 carcinoma of the vulva (not ame- nable to resection by standard radical vulvectomy) or recurrent disease (after incomplete resection). Tumor resectability was reas- sessed in patients who had responded to chemotherapy. Methods. The regimen consisted of bleomycin 5 mg intramus- cular (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 bleomycin 5 mg im days 1 and 4, and methotrexate 15 mg po on day 1 of the week. This 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 primary locally advanced disease, 13 patients had a locoregional recurrence, and all received up to three BMC cycles. Two complete and twelve partial responses were observed (response rate, 56%; 95%confidence limits, 35–76%). The BMC regimen was associated with major hematological side effects and mild 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 unknown cause. The median progres- sion-free survival was 4.8 months and the median survival was 7.8 months. The 1-year survival was 32% (95% confidence limits, 13–51%). Conclusion. The present data confirm the therapeutic activity of the BMC regimen in locoregionally advanced or recurrent squa- mous-cell carcinoma of the vulva. Following neoadjuvant chemo- therapy, the overall response rate was 56%. BMC is an outpatient treatment that may play a role in the palliative therapy of ad- vanced or recurrent vulva cancer. © 2001 Academic Press Key Words: vulva; cancer; phase II trial; chemotherapy; bleo- mycin; methotrexate; CCNU. INTRODUCTION Squamous-cell carcinoma of the vulva is a relatively rare disease that accounts for 4 – 8% of gynecological cancers [1]. Although vulvar carcinoma is mainly detected at an early stage, a consistent number of patients present with advanced disease at the time of diagnosis [2, 3]. Tumors are classified according to the International Federation of Gynecology and Obstetrics (FIGO) for carcinoma of the vulva. The 5-year survival for stage III and IV disease as reported in the FIGO annual report is 43.8 and 8.3%, respectively [3]. A quarter of patients with squamous-cell carcinoma of the vulva will either have inoperable primary disease or develop local recurrence [4]. To reduce the need for radical surgery, including pelvic exenteration, combinations of chemo- or ra- diotherapy and surgery have been explored [5]. 1 This publication was supported by a grant from the Dutch Cancer Society (Amsterdam, The Netherlands). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the Dutch Cancer Society. 2 To whom correspondence should be addressed at Division of Gynecology, European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy. Fax: +39 2 57 48 92 11. E-mail: nicoletta.colombo@ieo.it. Gynecologic Oncology 81, 348 –354 (2001) doi:10.1006/gyno.2001.6180, available online at http://www.idealibrary.com on 348 0090-8258/01 $35.00 Copyright © 2001 by Academic Press All rights of reproduction in any form reserved.