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GM-CSF, carboplatin, doxorubicin: a phase I study
E A Poplin1, D S Alberts, J J Rinehart
1Wayne State University Medical Center, Detroit, MI 48201.
Cancer Chemotherapy and Pharmacology
|January 1, 1994
Summary
Dose-intensified chemotherapy with carboplatin and doxorubicin showed dose-limiting thrombocytopenia. Granulocyte-macrophage colony-stimulating factor (GM-CSF) did not prevent severe myelosuppression in this phase I study.
Area of Science:
- Oncology
- Pharmacology
- Clinical Trials
Background:
- Dose intensification of chemotherapy can improve response rates in chemosensitive tumors.
- Granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) may permit dose escalation by mitigating myelosuppression.
Purpose of the Study:
- To determine the maximum tolerated dose (MTD) of carboplatin combined with a fixed dose of doxorubicin.
- To evaluate the effect of adding GM-CSF to dose-escalated carboplatin and doxorubicin therapy.
Main Methods:
- A phase I clinical trial involving 21 eligible patients, 13 with prior therapy.
- Doxorubicin (60 mg/m2) was administered every 28 days with escalating doses of carboplatin (250, 325, and 400 mg/m2).
- GM-CSF (10 mg/kg/day on days 1-21) was added during carboplatin dose escalation.
Main Results:
- Thrombocytopenia was the dose-limiting toxicity at carboplatin 400 mg/m2 and doxorubicin 60 mg/m2.
- The addition of GM-CSF did not permit further dose escalation and was associated with grade 4 granulocytopenia and thrombocytopenia in 4 and 5 of 6 patients, respectively.
- Thrombocytopenia severity correlated with carboplatin AUC, baseline platelet count, and prior therapy.
Conclusions:
- Carboplatin at 400 mg/m2 combined with doxorubicin 60 mg/m2 is not tolerated without significant myelosuppression.
- GM-CSF did not mitigate severe thrombocytopenia and granulocytopenia at these doses, suggesting a complex interaction with carboplatin-based chemotherapy.