Phase I study of escalating dose mitoxantrone in combination with α-2-interferon in patients with advanced solid tumors

Giampietro Gasparini, Sandro Dal Fior, Franco Pozza, Gino Antonio Panizzoni, Silvia Favretto, Daniel D. Von Hoff

Research output: Contribution to journalArticlepeer-review


In vitro and preclinical in vivo data have shown a synergistic antitumor activity between α-interferon and some antiproliferative agents. A phase I study of the concurrent administration of interferon-α 2 and mito-xantrone 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 α 2 (6 × 106 IU three times per week3), 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 > 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 a 2 were observed in all dose-levels explored. These observations suggest that the hepatotoxic effects of interferon a 2 do not emphasize mitoxantrone side-effects if given simultaneously. When mitoxantrone is administered with 6 × 106 IU of interferon α 2, the recommended dose for future phase II studies is 10 mg/m2/weeks3 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. In conclusion the concomitant administration of recombinant interferon α 2 and mitoxantrone allows the possibility to give a therapeutic dosage of both agents. Because the combination of the two agents was fairly well tolerated and antitumor activity was observed, phase II trials are warranted.

Original languageEnglish
Pages (from-to)245-252
Number of pages8
JournalInvestigational New Drugs
Issue number3
Publication statusPublished - Aug 1991


  • α-interferon
  • mitoxantrone
  • phase I trial

ASJC Scopus subject areas

  • Pharmacology
  • Molecular Medicine


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