Chemoimmunotherapy with bleomycin, vincristine, lomustine, dacarbazine (BOLD), and human leukocyte interferon for metastatic uveal melanoma

Abstract

BACKGROUNDA Phase II trial comprising patients with metastatic uveal melanoma (Stage IVB) was undertaken to determine the activity of bleomycin, vincristine, lomustine, and dacarbazine (BOLD) chemotherapy with human leukocyte interferon, as well as the progression‐free and overall survival of the patients according to the substage before treatment.METHODSTwenty‐two patients with histologically proven metastatic uveal melanoma received 15 mg of bleomycin (Days 2 and 5), 1 mg/m2 vincristine (Days 1 and 4), 200 mg/m2 dacarbazine (Days 1 to 5), and 80 mg lomustine (Day 1) every 4 weeks together with a leukocyte interferon preparation (3 × 106 IU daily for 6 weeks followed by 6 × 106 IU three times per week).RESULTSOf 20 evaluable patients, 3 (15%; 95% confidence interval [CI] 0–38) obtained a partial objective response in hepatic and extrahepatic sites and 11 (55%; 95% CI 32–77) showed stable disease after receiving more than two cycles. The median progression‐free survival was 4 months (95% CI 2–10) and the median overall survival was 12 months (95% CI 8–22). Eleven patients who had favorable pretreatment characteristics (Stage IVBa) survived a median of 17 months (95% CI 4–37) whereas 10 patients with less favorable characteristics (Stage IVBb) survived a median of 11 months (95% CI 1–23). Moderate toxicity occurred with this outpatient regimen.CONCLUSIONSThe BOLD/human leukocyte interferon regimen had modest activity against metastatic uveal melanoma in hepatic and extrahepatic sites. The median overall survival approached that reported for more aggressive intrahepatic therapy regimens. Substage differences can significantly impact study outcomes. Therefore, substage information should be reported to facilitate comparisons between studies. Cancer 2002;95:2366–72. © 2002 American Cancer Society.DOI 10.1002/cncr.10996

Management of Uveal Melanoma: A Consensus-Based Provincial Clinical Practice Guideline

“…Furthermore, most systemic therapies for metastatic uveal melanoma (largely modelled after therapies for cutaneous melanoma) have failed to demonstrate clinical efficacy in phase ii trials [65][66][67][68][69][70][71][72][73][74][75][76][77][78][79][80][81] . However, immunotherapies, including the anti-ctla4 antibody ipilimumab, have shown some success in retrospective and expanded-access studies [82][83][84][85][86][87] .…”

Uveal Melanoma: A Review of the Literature

“…Several chemotherapeutic and immunomodulatory agents have been examined in patients with uveal melanoma; however, response rates have been low (less than 5%), with median overall survival ranging from 6 to 14 months [126][127][128][129][130][131][132][133][134][135][136][137].…”

Combined Immunologic and Anti-Angiogenic Therapy Reduces Hepatic Micrometastases in a Murine Ocular Melanoma Model

“…32,33 However, a prospective study from Europe failed to show the effect of the combination of bleomycin, vincristine, lomustine, and dacarbazine (BOLD) and recombinant interferon alpha-2b treatment on metastatic uveal melanoma. 34 A series of experiments investigating the relationship between c-myc expression and interferon sensitivity in uveal melanoma seems to explain why interferon may fail to be effective against metastatic uveal melanoma in some instances.…”