title: Bleomycin, methotrexate, and CCNU in locally advanced or recurrent, inoperable, squamous-cell carcinoma of the vulva: an EORTC Gynaecological Cancer Cooperative Group Study. European Organization for Research and Treatment of Cancer.
abstract: OBJECTIVE
  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 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 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 progression-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%).
  
  
  CONCLUSIONS
  The present data confirm the therapeutic activity of the BMC regimen in locoregionally advanced or recurrent squamous-cell carcinoma of the 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.
authors.affiliation: Department of Gynaecology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: H C
authors.initials: HC
authors.lastname: Wagenaar
authors.forename: N
authors.initials: N
authors.lastname: Colombo
authors.forename: I
authors.initials: I
authors.lastname: Vergote
authors.forename: G
authors.initials: G
authors.lastname: Hoctin-Boes
authors.forename: G
authors.initials: G
authors.lastname: Zanetta
authors.forename: S
authors.initials: S
authors.lastname: Pecorelli
authors.forename: A J
authors.initials: AJ
authors.lastname: Lacave
authors.forename: Q
authors.initials: Q
authors.lastname: van Hoesel
authors.forename: A
authors.initials: A
authors.lastname: Cervantes
authors.forename: G
authors.initials: G
authors.lastname: Bolis
authors.forename: M
authors.initials: M
authors.lastname: Namer
authors.forename: C
authors.initials: C
authors.lastname: Lhommé
authors.forename: J P
authors.initials: JP
authors.lastname: Guastalla
authors.forename: M A
authors.initials: MA
authors.lastname: Nooij
authors.forename: A
authors.initials: A
authors.lastname: Poveda
authors.forename: V
authors.initials: V
authors.lastname: Scotto di Palumbo
authors.forename: J B
authors.initials: JB
authors.lastname: Vermorken
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001761:Bleomycin / Q000008:administration & dosage / Q000009:adverse effects; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000601:surgery; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008130:Lomustine / Q000008:administration & dosage / Q000009:adverse effects; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000601:surgery; D011446:Prospective Studies; D014846:Vulvar Neoplasms / Q000188:drug therapy* / Q000601:surgery
chemical_list: D000970:Antineoplastic Agents; D001761:Bleomycin; D008130:Lomustine; D008727:Methotrexate