Phase I study of alpha 2-interferon plus doxorubicin in patients with solid tumors

Cytotoxic chemotherapy and interferon have shown synergistic antitumor activity in vitro. The purpose of this study was to determine the maximally tolerated dose of doxorubicin given every 3 weeks, in patients receiving recombinant alpha 2-interferon [10 X 10(6) IU/m2 s.c. three times per week (Monday, Wednesday, and Friday)] during the first 2 weeks of each cycle of doxorubicin. Fourteen patients received a total of 41 cycles. Hematological toxicity was dose limiting with granulocytopenia (total granulocyte count, less than 1000) occurring in 50% of patients treated with doxorubicin at 40 mg/m2 and in 25% of patients treated with doxorubicin at 30 mg/m2. Nonhematological toxicities included a flu-like syndrome, alopecia, nausea, vomiting, diarrhea, and transient mild increases in liver function tests. A partial response was seen in one patient with metastatic squamous cell carcinoma of the skin and in another patient with metastatic adenocarcinoma of the pancreas. Concomitant administration of recombinant alpha 2-interferon given on this schedule limits the amount of doxorubicin that can be administered. However, the responses noted in this study are encouraging enough to warrant additional studies of doxorubicin plus recombinant alpha 2-interferon.