title: Chemoimmunotherapy with bleomycin, vincristine, lomustine, dacarbazine (BOLD) plus interferon alpha for metastatic melanoma: a multicentre phase II study.
abstract: High response rates in patients with metastatic melanoma have been achieved with combination chemoimmunotherapy. A response rate of 62% in 45 patients has been reported for treatment with dacarbazine, bleomycin, vincristine, lomustine (BOLD) plus interferon alpha (IFN-alpha). We conducted a multicentre phase II study to confirm these results. Melanoma patients with distant metastases were treated as outpatients with dacarbazine 200 mg m(-2) on days 1-5, vincristine 1 mg m(-2) on days 1 and 4, bleomycin 15 mg on days 2 and 5 i.v. and lomustine 80 mg orally on day 1, repeated every 4 weeks. IFN-alpha-2b was initiated s.c. on day 8 at 3 MU daily for 6 weeks, and 6 MU t.i.w. thereafter. Forty-three patients entered the study. The median number of metastatic sites was three (range 1-5), and 81% of patients had visceral metastases. Nine patients had brain metastases, and seven patients were systemically pretreated. Among the 41 patients that were evaluable for response, the response rate was 27% (95% CI 14-3%), with one complete and ten partial remissions. The response rate in 25 previously untreated patients without brain metastases was 40% (95% CI 21-61%). Median duration of response was 6 (range 2-14+) months; median overall survival was 5 (1-26) months. The main toxicity was malaise/fatigue. We confirm that BOLD plus IFN-alpha has activity in metastatic melanoma. The lower response rate in our study compared with the previous report is probably related to patient selection, as in the previous study 46% of patients had stage III disease, whereas all our patients had stage IV disease, which is associated with a worse prognosis.
authors.affiliation: Department of Medical Oncology, University Hospital Nijmegen, The Netherlands.
authors.forename: C J
authors.initials: CJ
authors.lastname: Punt
authors.forename: C M
authors.initials: CM
authors.lastname: van Herpen
authors.forename: R L
authors.initials: RL
authors.lastname: Jansen
authors.forename: G
authors.initials: G
authors.lastname: Vreugdenhil
authors.forename: E W
authors.initials: EW
authors.lastname: Muller
authors.forename: P H
authors.initials: PH
authors.lastname: de Mulder
mesh_terms: D000008:Abdominal Neoplasms / Q000556:secondary / Q000628:therapy*; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001761:Bleomycin / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000556:secondary / Q000628:therapy*; D003606:Dacarbazine / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007167:Immunotherapy; D016898:Interferon-alpha / Q000009:adverse effects / Q000627:therapeutic use*; D008130:Lomustine / Q000627:therapeutic use; D008297:Male; D008545:Melanoma / Q000556:secondary / Q000628:therapy*; D008875:Middle Aged; D009367:Neoplasm Staging; D012878:Skin Neoplasms / Q000473:pathology / Q000628:therapy*; D016896:Treatment Outcome; D014750:Vincristine / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D016898:Interferon-alpha; D001761:Bleomycin; D014750:Vincristine; D008130:Lomustine; D003606:Dacarbazine