In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 18, No. 18 ( 2000-09-18), p. 3288-3294
Abstract:
PURPOSE: The sequence in which chemotherapeutic agents are administered can alter their pharmacokinetics, therapeutic effect, and toxicity. We evaluated the pharmacokinetics and pharmacodynamics of docetaxel and topotecan when coadministered on two different sequences of administration. PATIENTS AND METHODS: On cycle 1, docetaxel was administered as a 1-hour infusion at 60 mg/m 2 without filgrastim and at 60, 70, and 80 mg/m 2 with filgrastim on day 1, and topotecan was administered at 0.75 mg/m 2 as a 0.5-hour infusion on days 1 to 4. On cycle 2, topotecan was administered on days 1 to 4, and docetaxel was administered on day 4. Cycles were repeated every 21 days. Blood samples for high-performance liquid chromatography measurement of docetaxel (CL DOC ) and topotecan (CL TPT ) total clearance were obtained on day 1 of cycle 1 and day 4 of cycle 2. CL DOC and CL TPT were calculated using compartmental methods. RESULTS: Mean ± SD CL DOC in cycles 1 and 2 were 75.9 ± 79.6 L/h/m 2 and 29.2 ± 17.3 L/h/m 2 , respectively (P 〈 .046). Mean ± SD CL TPT in cycles 1 and 2 were 8.5 ± 4.4 L/h/m 2 and 9.3 ± 3.4 L/h/m 2 , respectively (P 〉 .05). Mean ± SD neutrophil nadir in cycles 1 and 2 were 4,857 ± 6,738/μL and 2,808 ± 4,518/μL, respectively (P = .02). CONCLUSION: Administration of topotecan on days 1 to 4 and docetaxel on day 4 resulted in an approximately 50% decrease in docetaxel clearance and was associated with increased neutropenia.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/JCO.2000.18.18.3288
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2000
detail.hit.zdb_id:
2005181-5
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