In vitro and preclinical in vivo data have shown a synergistic antitumor activity between alpha-interferon and some antiproliferative agents. A phase I study of the concurrent administration of interferon-alpha 2 and mitoxantrone was initiated, to determine the maximum tolerated dose of mitoxantrone given i.v. every 3 weeks in escalating doses combined with a fixed dose of s.c. interferon alpha 2 (6 x 10(6) IU three times per week 3), in patients with advanced solid tumors resistant to conventional chemotherapy. At least three evaluable patients were entered in each dose level of mitoxantrone starting at 4 mg/m2, with no escalations allowed in the same patient. Twenty-seven patients received a total of 101 cycles and five dose-levels were explored (4-6-8-10-12 mg/m2 of mitoxantrone). The dose-limiting toxicities were leukopenia and granulocytopenia at 12 mg/m2 of mitoxantrone, at which dose hematological toxicity occurred in greater than 50% of cases, with one patient presenting grade 4 leuko-granulocytopenia. No severe thrombocytopenia occurred. In the majority of patients transient hepatic enzyme elevations and a flu-like syndrome due to interferon alpha 2 were observed in all dose-levels explored. These observations suggest that the hepatotoxic effects of interferon alpha 2 do not emphasize mitoxantrone side-effects if given simultaneously. When mitoxantrone is administered with 6 x 10(6) IU of interferon alpha 2, the recommended dose for future phase II studies is 10 mg/m2/weeks 3 with escalation up to 12 mg/m2 in selected patients if such a combination is well tolerated in terms of myelosuppression. Regarding therapeutic activity, four out of 25 (16%) cases evaluable for response achieved a partial response.(ABSTRACT TRUNCATED AT 250 WORDS)