期刊
ONCOLOGIST
卷 19, 期 9, 页码 959-965出版社
ALPHAMED PRESS
DOI: 10.1634/theoncologist.2014-0132
关键词
Fluorouracil; Pharmacokinetic; Dosing; Colorectal; Community; Personalized
类别
资金
- Myriad Genetics, Inc.
Background. Pharmacokinetically guided (PK-guided) versus body surface area-based 5-fluorouracil (5-FU) dosing results in higher response rates and better tolerability. A paucity of data exists on PK-guided 5-FU dosing in the community setting. Patients and Methods. Seventy colorectal cancer patients, from one academic and five community cancer centers, received the mFOLFOX6 regimen (5-FU 2,400 mg/m(2) over 46 hours every 2 weeks) with or without bevacizumab at cycle 1. The 5-FU continuous-infusion dose was adjusted for cycles 2-4 using a PK-guided algorithm to achieve a literature-based target area under the concentration-time curve (AUC). The primary objective was to demonstrate that PK-guided 5-FU dosing improves the ability to achieve a target AUC within four cycles of therapy. The secondary objective was to demonstrate reduced incidence of 5-FU-related toxicities. Results. At cycles 1 and 4, 27.7% and 46.8% of patients achieved the target AUC (20-25 mg 3 hour/L), respectively (odds ratio [OR]: 2.20; p 5.046). Significantly more patients were within range at cycle 4 compared with a literature rate of 20% (p < .0001). Patients had significantly higher odds of not being underdosed at cycle 4 versus cycle 1 (OR: 2.29; p = .037). The odds of a patient being within range increased by 30% at each subsequent cycle (OR: 1.30; p = 5.03). Less grade 3/4 mucositis and diarrhea were observed compared with historical data(1.9% vs16% and 5.6% vs 12%, respectively); however, rates of grade 3/4 neutropenia were similar (33% vs 25%-50%). Conclusion. PK-guided 5-FU dosing resulted in significantly fewer underdosed patients and less gastrointestinal toxicity and allows for the application of personalized colorectal cancer therapy in the community setting.
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