GM-CSF, carboplatin, doxorubicin: a phase I study

Elizabeth A. Poplin, David S. Alberts, John J. Rinehart, Harriet O. Smith, James A. Neidhart, Evan M. Hersh

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Dose intensification has the potential to increase the response frequency of chemosensitive tumors to chemotherapy. G-CSF and GM-CSF offer the possibility of dose-intensifying chemotherapy without prohibitive myelosuppression. A phase I study was undertaken to identify the maximum tolerated dose (MTD) of carboplatin that could be administered with a fixed dose of doxorubicin, 60 mg/m2, administered every 28 days. Further escalation of the carboplatin dose was then attempted, with the concomitant addition of GM-CSF 10 mg/kg per day on days 1-21. We had 21 patients, 13 with prior therapy, who were eligible. In all, 60 courses of therapy were delivered, all with doxorubicin and with carboplatin doses of 250 mg/m2, 325 mg/m2 and 400 mg/m2. At carboplatin 400 mg/m2 and doxorubicin 60 mg/m2, thrombocytopenia was dose limiting. The addition of GM-CSF did not allow further escalation. Of the 6 patients treated with carboplatin 400 mg/m2, doxorubicin 60 mg/m2, and GM-CSF, grade 4 granulocytopenia and thrombocytopenia were seen in 4 and 5 patients, respectively. The severity of thrombocytopenia was related to the calculated carboplatin AUC and also to baseline platelet count and prior therapy. In addition, the interaction of GM-CSF and chemotherapy, especially carboplatin-based, may be more complex than originally anticipated.

Original languageEnglish (US)
Pages (from-to)340-346
Number of pages7
JournalCancer Chemotherapy and Pharmacology
Volume33
Issue number4
DOIs
StatePublished - Jul 1 1994

ASJC Scopus subject areas

  • Oncology
  • Toxicology
  • Pharmacology
  • Cancer Research
  • Pharmacology (medical)

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  • Cite this

    Poplin, E. A., Alberts, D. S., Rinehart, J. J., Smith, H. O., Neidhart, J. A., & Hersh, E. M. (1994). GM-CSF, carboplatin, doxorubicin: a phase I study. Cancer Chemotherapy and Pharmacology, 33(4), 340-346. https://doi.org/10.1007/BF00685910