Long-Term Survival in Metastatic Melanoma Patients Treated with Sequential Biochemotherapy: Report of a Phase II Study

Abstract

The overall survival for patients with metastatic melanoma is very poor, with a median survival of 8.5 months. In this Phase II trial, we assessed the efficacy, safety, and tolerability of a sequential biochemotherapy schedule, using dacarbazine as antiblastic agent and immunomodulant doses of interleukin-2 and interferon-alfa. Thirty-one eligible patients with metastatic melanoma received dacarbazine IV as antiblastic therapy and interluekin-2, plus interferon-alfa SC as sequential immunotherapy, for 6 months. Responding and nonprogressing patients were subsequently maintained on immunotherapy treatment for further 6 months. Twenty-nine patients had an adequate trial, and were assessable for both response and toxicities, with a median follow-up of 49 months. The overall response rate was 52 percent (3 CR and 12 PR), SD was 8 (27 percent) and PD were achieved in 6 patients (21 percent). The median survival duration of responders was 28 months, significantly longer (p < 0.001) than the 16 months of nonresponders. Therapy was well tolerated and produced a significant improvement in progressive-free survival. Further studies, thus, are recommended for larger groups of patients not only to confirm these results, but also to apply this biochemotherapy regimen as adjuvant postsurgical treatment in early stages of malignant melanoma.

Outcomes of melanoma in recipients of solid organ transplant

“…23,24 Many melanoma vaccines are designed to use dendritic cells to present antigen and initiate the T-cell response through both naïve and memory CD8 1 and CD4 1 T lymphocytes. Attempts to use interleukin 2 to stimulate an immune response have shown some promise, 25 and other studies have shown that patients with advanced cancer produce less T H 1 cytokines in response to stimulation than do healthy control subjects. 6 Immunosuppressive medications used in solid organ transplant recipients have a primary focus of inhibiting T-cell activation.…”

“…Cases of metastatic MM transmitted with the donated organs leading to high mortality in the recipients [20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36] have been reported. Penn 33 recorded data of 13 donors with MM who provided organs to 28 recipients.…”

Pharmacological targeting of guanosine monophosphate synthase suppresses melanoma cell invasion and tumorigenicity

“…Its ability to metastasize in combination with resistance to conventional anticancer chemotherapy makes melanoma extremely difficult to cure, and the median survival of patients with metastatic melanoma is 8.5 months. [1][2][3] A better understanding of the biology behind melanoma aggressiveness is imperative to facilitate the development of novel anti-melanoma strategies.…”