A southwest oncology group phase i study of the sequential combination of recombinant interferon-γ and recombinant interleukin-2 in patients with cancer

Thirty-seven patients with advanced malignancies were treated sequentially with recombinant interferon-γ (rIFN-γ) and recombinant interleukin-2 (rIL-2) in an outpatient dose escalation clinical trial. rIFN-γ (0.1 or 0.25 mg/m²/day) was administered by intramuscular injection, days 1–7 and rIL-2 (12, 18, or 24 x 10⁶IU/m²/day) was administered by a 15-min intravenous bolus, days 8–12. Common toxicities encountered included fever, chills, fatigue, neutropenia, and elevations of SGOT, bilirubin, or creatinine. Hypotension and cardiac and pulmonary toxicities were rare. With repeated cycles of therapy, nausea/vomiting and diarrhea associated with the administration of rIL-2 were seen in greater frequency. There were no treatment-related deaths, and no patient required intensive care unit admission for toxicity management. A complete response was observed in one of 11 patients with renal cancer and a partial response was observed in one of seven patients with malignant melanoma. Due to problems with drug supply, further dose escalation could not be continued, and maximum tolerated doses (MTD) were not determined by strict criteria. However, the combination of rIFN-γ, 0.25 mg/m²/day, and rIL-2, 24 x 10⁶IU/m²/day, appeared to be beyond the MTD, as three of six patients at this dose level could not complete one cycle of therapy due to toxicity, and for further study using this schedule, we recommend the doses: Rifn-γ, 0.1 mg/m²/day, and rIL-2, 24 x 10⁶IU/m²/day.