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 (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.