ATLANTAResearchers at the Karmanos Cancer Institute/Wayne State University, Detroit, and the Cytokine Working Group report encouraging response rates and acceptable toxicity using an outpatient regimen for metastatic malignant melanoma. The phase II trial combined cisplatin(Drug information on cisplatin) (Platinol) and DTIC chemotherapy with interleukin-2 (IL-2) and interferon-alfa biotherapy.
Many past international trials combining various chemotherapy regimens with biotherapy required inpatient management due to toxicity, Lawrence E. Flaherty, MD, associate director, Karmanos Cancer Institute, said at the 35th Annual Meeting of the American Society of Clinical Oncology. In addition, unlike other outpatient trials that generally gave IL-2 subcutaneously, the Cytokine Working Group administered IL-2 intravenously in one arm of its study.
On days 1, 2, and 3, all patients were given intravenous DTIC (250 mg/m²/day) and cisplatin (25 mg/m²/d). On days 6, 8, 10, 13, and 15, all patients received subcutaneous interferon-alfa (5 MIU/m²), which was then repeated every 4 weeks. Patients were aso randomized to receive bolus intravenous IL-2 (18 MIU/m²/d) on days 6 through 10 and 13 through 15 or subcutaneous IL-2 (5 MIU/m²/d) in the same schedule.
Of the 43 patients in the IV arm evaluable for response, five (12%) had a complete remission, and 11 (25%) a partial remission, for a 37% response rate. Of 36 evaluable patients in the subcutaneous arm, one had a complete remission (3%), and five a partial remission (14%), for a 17% response rate. As of this interim report, Dr. Flaherty reported that the survival curves are comparable.
These outpatient regimens can be administered with an acceptable toxicity profile, he said. The incidence of gastrointestinal toxicity was slightly greater in the IV arm, as was neutropenia. However, Dr. Flaherty said, there were no hospital admissions in either arm for neutropenic fever with over 250 cycles delivered. Thirteen patients required re-hospitalization8 in the IV arm and 5 in the subcutaneous arm.
Toxicities (grade 3 or 4) for the IV arm (148 cycles) and the subcutaneous arm (114 cycles), respectively, were as follows: nausea/vomiting, 7% vs 3%; fatigue, 3% vs 2%; renal, 0% vs 2%; neutropenia, 21% vs 11%; and thrombocytopenia, 6% vs 7%. Dose reductions were needed in 6% of patients in both arms.
Dr. Flaherty noted that responses were more encouraging in the IV arm, especially among those patients with visceral involvement, making it the preferred regimen for future phase III trials.
The results are particularly relevant, he said, because this study, unlike most biochemotherapy trials in metastatic malignant melanoma, was conducted in a multi-institutional setting.