Related Experiment Videos
Sequence-dependent hematological toxicity associated with the 3-hour paclitaxel/cyclophosphamide doublet
M J Kennedy1, M L Zahurak, R C Donehower
1Johns Hopkins Oncology Center, Baltimore, Maryland 21287, USA. jkennedy@welchlink.welch.jhu.edu
Summary
This study found that severe myelosuppression limited the dose of paclitaxel and cyclophosphamide combination therapy for metastatic breast cancer. Hematologic toxicity was worse when paclitaxel was given before cyclophosphamide, regardless of administration time.
Area of Science:
- Oncology
- Pharmacology
- Clinical Trials
Background:
- Paclitaxel is effective for metastatic breast cancer.
- Combination chemotherapy can have complex, sequence-dependent effects.
- Previous studies noted sequence-dependent toxicity with 24-hour paclitaxel infusions.
Purpose of the Study:
- Determine maximum tolerated doses (MTD) of paclitaxel (3-h infusion) and cyclophosphamide.
- Assess if sequence-dependent toxicities persist with shorter paclitaxel infusion.
- Evaluate drug sequencing impact on toxicity and pharmacokinetics.
Main Methods:
- Fifteen women with metastatic breast cancer received escalating doses of paclitaxel and cyclophosphamide every 3 weeks.
- Granulocyte colony-stimulating factor (Filgrastim) was administered prophylactically.
- Drug administration sequence (paclitaxel first vs. cyclophosphamide first) was alternated.
Main Results:
- Severe myelosuppression was the dose-limiting toxicity, establishing the MTD at 200 mg/m² paclitaxel and 1600 mg/m² cyclophosphamide.
- Hematological toxicity was significantly more severe when paclitaxel preceded cyclophosphamide.
- No sequence-dependent pharmacokinetic differences were observed.
Conclusions:
- The MTD for this paclitaxel/cyclophosphamide regimen with G-CSF support was determined.
- Sequence-dependent hematological toxicity was observed even with a 3-hour paclitaxel infusion.
- Drug sequencing is a critical factor in developing combination therapies with paclitaxel and alkylating agents.