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

BACKGROUND A 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. METHODS Twenty‐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). RESULTS Of 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. CONCLUSIONS The 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 Systemic dacarbazine‐based combination chemotherapy was administered with human leukocyte interferon to patients with metastatic uveal melanoma. This regimen gave a modest 15% objective response rate and a median overall survival of 17 and 11 months, respectively, among patients with a favorable and less favorable prognosis, respectively, based on pretreatment characteristics. It is useful to report survival according to prognostic categories to aid assessing lead time bias in nonrandomized trials of rare cancers.