PURPOSE: The primary objective of this clinical study was to assess the feasibility of administering recombinant interleukin-2 and recombinant interferon alfa-2a before and after combination cytotoxic chemotherapy. After encouraging initial responses, the study was expanded to further evaluate the therapeutic potential, clarify the toxicities of this regimen, and explore any associated immunologic changes. PATIENTS AND METHODS: Eighty-four patients with metastatic melanoma, including patients with brain metastases, were treated on this 6-week protocol. Patients received combination cisplatin (25 mg/m2/d) and dacarbazine (220 mg/m2/d) on days 1 through 3 and 22 through 24 plus carmustine (150 mg/m2) on day 1. Interleukin 2 (13.5 million IU/m2/d) and interferon alfa (6 MU/m2/d) were administered on days 4 through 8 and 17 through 21. RESULTS: Among 83 patients assessable for response, 12 complete and 34 partial responses were documented (55% response rate). The median time to disease progression was 7 months, the median survival from study entry was 12.2 months, and the median survival from diagnosis of metastatic disease was 15.5 months. Although patients were hospitalized to receive treatment, intensive care unit support generally was not needed. Dose-limiting toxicities were related to elevations in serum bilirubin and serum creatinine levels. No patient developed a grade 4 clinical toxicity. Treatment produced a skin depigmentation, which was associated with prolonged survival. CONCLUSION: A plateau in both the survival and time to progression curves beyond 2 years (15% of the patients) and a greater than 10% disease-free survival beyond 4 years indicate that there may be a long-term benefit for some patients. The limited toxicity of this regimen should permit its use in most oncology settings. A randomized trial of chemoimmunotherapy versus chemotherapy should be performed to establish the value of chemoimmunotherapy for melanoma.
RCT Entities:
PURPOSE: The primary objective of this clinical study was to assess the feasibility of administering recombinant interleukin-2 and recombinant interferon alfa-2a before and after combination cytotoxic chemotherapy. After encouraging initial responses, the study was expanded to further evaluate the therapeutic potential, clarify the toxicities of this regimen, and explore any associated immunologic changes. PATIENTS AND METHODS: Eighty-four patients with metastatic melanoma, including patients with brain metastases, were treated on this 6-week protocol. Patients received combination cisplatin (25 mg/m2/d) and dacarbazine (220 mg/m2/d) on days 1 through 3 and 22 through 24 plus carmustine (150 mg/m2) on day 1. Interleukin 2 (13.5 million IU/m2/d) and interferon alfa (6 MU/m2/d) were administered on days 4 through 8 and 17 through 21. RESULTS: Among 83 patients assessable for response, 12 complete and 34 partial responses were documented (55% response rate). The median time to disease progression was 7 months, the median survival from study entry was 12.2 months, and the median survival from diagnosis of metastatic disease was 15.5 months. Although patients were hospitalized to receive treatment, intensive care unit support generally was not needed. Dose-limiting toxicities were related to elevations in serum bilirubin and serum creatinine levels. No patient developed a grade 4 clinical toxicity. Treatment produced a skin depigmentation, which was associated with prolonged survival. CONCLUSION: A plateau in both the survival and time to progression curves beyond 2 years (15% of the patients) and a greater than 10% disease-free survival beyond 4 years indicate that there may be a long-term benefit for some patients. The limited toxicity of this regimen should permit its use in most oncology settings. A randomized trial of chemoimmunotherapy versus chemotherapy should be performed to establish the value of chemoimmunotherapy for melanoma.
Authors: Kazuo Koyanagi; Steven J O'Day; Rene Gonzalez; Karl Lewis; William A Robinson; Thomas T Amatruda; He-Jing Wang; Robert M Elashoff; Hiroya Takeuchi; Naoyuki Umetani; Dave S B Hoon Journal: J Clin Oncol Date: 2005-11-01 Impact factor: 44.544
Authors: Simon Pacey; Martin Gore; David Chao; Udai Banerji; James Larkin; Sarah Sarker; Karen Owen; Yasmin Asad; Florence Raynaud; Mike Walton; Ian Judson; Paul Workman; Tim Eisen Journal: Invest New Drugs Date: 2010-08-05 Impact factor: 3.850
Authors: Kazuo Koyanagi; Takuji Mori; Steven J O'Day; Steve R Martinez; He-Jing Wang; Dave S B Hoon Journal: Cancer Res Date: 2006-06-15 Impact factor: 12.701
Authors: K Margolin; J Longmate; T W Synold; D R Gandara; J Weber; R Gonzalez; M J Johansen; R Newman; T Baratta; J H Doroshow Journal: Invest New Drugs Date: 2001 Impact factor: 3.850
Authors: Michael G Smylie; Ralph Wong; Catalin Mihalcioiu; Chris Lee; Jean-Francois Pouliot Journal: Invest New Drugs Date: 2006-09-07 Impact factor: 3.850
Authors: Michael B Atkins; Jessie Hsu; Sandra Lee; Gary I Cohen; Lawrence E Flaherty; Jeffrey A Sosman; Vernon K Sondak; John M Kirkwood Journal: J Clin Oncol Date: 2008-11-10 Impact factor: 44.544