Multicenter phase II study of chemoimmunotherapy in the treatment of metastatic melanoma

Abstract

Combining chemotherapy and immunotherapeutic agents such as interleukin-2 and interferon alpha-2b might improve treatment results in metastatic melanoma (MM) patients compared with chemotherapy alone. This prospective study evaluated the potential efficacy of a biochemotherapy regimen followed by maintenance biotherapy for the treatment of MM. Twenty-two patients with stage IV melanoma were treated for 5 consecutive days with cisplatin at 20 mg/m, vinblastine at 1.6 mg/m, and dacarbazine at 160 mg/m. Pegylated interferon alpha-2b at a dose of 50 microg every week, subcutaneous interleukin-2, 1.8 MIU, and oral 13-cis-retinoic acid (13-cis-RA) at 0.5 mg/kg were given 5 days/week for 3 weeks each month during the period of chemotherapy administration. Maintenance biotherapy was continued in patients who had a complete or partial response or disease stability (clinical benefit) after six courses of biochemotherapy. The primary endpoint was response; secondary endpoints were the evaluation of the immunologic parameters, toxicity, progression-free survival, and overall survival. Twelve patients (54.5%) achieved a response, and seven (31.8%) maintained stable disease for at least 6 months with maintenance biotherapy. The median progression-free survival and overall survival were 23.3 and 45.7 months, respectively. The most important toxicities from chemotherapy were grades 3 and 4 neutropenia and thrombocytopenia in 41 and 18% of patients, respectively, whereas grade 2 autoimmune reactions were observed in 21% of patients after maintenance biotherapy. A prolonged enhancement of immunologic function was observed in the 19 patients treated with maintenance therapy. A regimen of six cycles of biochemotherapy followed by maintenance immunotherapy is well tolerated, and shows significant activity in patients with MM.

Radiopharmaceutical Therapy of Patients with Metastasized Melanoma with the Melanin-Binding Benzamide 131I-BA52

“…Metastatic malignant melanoma remains an incurable disease in many patients, and the 5-y survival rate for stage IV melanoma is still 15%-20% (9). A few years ago, specific tumor geno-and phenotypes were identified that present higher response rates to various targeted treatments, such as the BRAF mutation V600E to treatment with the tyrosine kinase inhibitor vemurafenib, NY-ESO-1 expression and immunotreatment with Ipilimumab (BristolMyers Squibb), or c-kit mutation to Imatinib (Novartis).…”

Synchronous Metastatic Melanoma Presenting as Gingival and Facial Swelling: A Case Report and Review of the Literature

“…Surgery is believed to be the most effective treatment for melanoma, and an adjuvant multimodal therapy might be beneficial, especially in patients with metastasis 60 . A good clinical course has also been obtained by immunotherapy with interferon 61 . The 5‐year overall survival rate of patients with primary oral melanoma is 15%, with a median survival of 25 months 29 .…”

Chemocentric Chemoimmunotherapy: A New Concept in Melanoma Immunotherapy

“…Median progression-free survival was 2.5 months, and toxicities were primarily hematological, including one treatment-related bleeding complication leading to death. A smaller study of 22 metastatic melanoma patients receiving a regimen of CVD with PEG-IFN-2b, subcutaneous IL-2 and oral 13-cis-retinoic acid, with maintenance biotherapy for those with clinical response after six courses, www.intechopen.com provided 12 objective responses with seven maintenance-receiving patients having stable disease after six months (Recchia et al, 2008). Median progression-free and overall survivals were 23.3 and 45.7 months, respectively, with mostly hematological toxicities and 21% of patients exhibiting grade 2 autoimmune reactions.…”