Randomized trial of dacarbazine versus bleomycin, vincristine, lomustine and dacarbazine (BOLD) chemotherapy combined with natural or recombinant interferon-alpha in patients with advanced melanoma.
This randomized phase II study was designed to compare the efficacy and tolerability of dacarbazine (DTIC) and bleomycin, vincristine, lomustine and DTIC (BOLD) combined with natural interferon-alpha (nIFN-alpha) or recombinant interferon-alpha2b (rIFN-alpha2b) in patients with advanced melanoma. The treatment arms were: A, DTIC plus nIFN-alpha; B, BOLD plus nIFN-alpha; C, DTIC plus rIFN-alpha2b; D, BOLD plus rIFN-alpha2b. One hundred and eight patients were randomized, of whom 106 were eligible to be analysed for efficacy. Overall, 56% of patients had abdominal visceral and/or bone involvement. The response rates were 8% (2/25) in arm A, 13% (4/31) in arm B, 12% (3/25) in arm C and 24% (6/25) in arm D. The differences were not statistically significant by the usual chi-squared test. However, when analysed using the Cochran-Armitage trend test, the one-sided P values were close to significant (0.085 and 0.033). All of the eight complete responses occurred in patients with soft tissue and/or lung metastases and the BOLD regimens produced six of them. There were no significant differences in survival (arm A, 11.1 months; arm B, 9.8 months; arm C, 9.1 months; arm D, 7.5 months; P=0.62). BOLD was more toxic than DTIC. With the present sample size, there were no statistically significant differences in efficacy between the arms, but there was a trend towards a higher response rate with BOLD plus rIFN-alpha2b. Patients with soft tissue or lung metastases may achieve more complete responses with BOLD regimens.
Vuoristo
Meri-Sisko
MS
Department of Oncology, University of Tampere and Tampere University Hospital, Tampere, Finland. meri-sisko.vuoristo@fimnet.fi
Hahka-Kemppinen
Marjo
M
Parvinen
Leena-Maija
LM
Pyrhönen
Seppo
S
Seppä
Hanna
H
Korpela
Merja
M
Kellokumpu-Lehtinen
Pirkko
P
D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D001761:Bleomycin / Q000008:administration & dosage / Q000627:therapeutic use; D003606:Dacarbazine / Q000008:administration & dosage / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007370:Interferon Type I / Q000627:therapeutic use*; D016898:Interferon-alpha / Q000627:therapeutic use*; D008130:Lomustine / Q000008:administration & dosage / Q000627:therapeutic use; D008297:Male; D008545:Melanoma / Q000188:drug therapy*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011994:Recombinant Proteins; D012878:Skin Neoplasms / Q000188:drug therapy*; D016019:Survival Analysis; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage / Q000627:therapeutic use
D000970:Antineoplastic Agents; D007370:Interferon Type I; D016898:Interferon-alpha; D011994:Recombinant Proteins; D001761:Bleomycin; D014750:Vincristine; D008130:Lomustine; D003606:Dacarbazine