Personalized Dosing via Pharmacokinetic Monitoring of 5-Fluorouracil Might Reduce Toxicity in Early- or Late-Stage Colorectal Cancer Patients Treated With Infusional 5-Fluorouracil-Based Chemotherapy Regimens

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• 作者：Christina Leah B. Kline¹ ; Angelique Schiccitano¹ ; Junjia Zhu² ; Cheryl Beachler¹ ; Hassan Sheikh¹ ; Harold A. Harvey¹ ; Heath B. Mackley¹ ; ³ ; Kevin McKenna⁴ ; Kevin Staveley-O'Carroll⁴ ; Lisa Poritz⁴ ; Evangelos Messaris⁴ ; David Stewart⁴ ; Jeffrey Sivik⁵ ; Wafik S. El-Deiry¹ ; ^{weldeiry@hmc.psu.edu" class="auth_mail}
• 关键词：Chemotherapy ; FOLFOX ; 5-FU ; OnDose ; Personalized cancer therapy
• 刊名：Clinical Colorectal Cancer
• 出版年：June 2014
• 年：2014
• 卷：13
• 期：2
• 页码：119-126
• 全文大小：496 K

文摘

Therapeutic plasma 5-fluorouracil (5-FU) levels are achieved in only 20% to 30% of patients with the current practice of administering 5-FU doses based on body surface area (BSA). Alternatively, 5-FU doses can be adjusted based on 5-FU pharmacokinetic (PK) monitoring. Although benefits of PK monitoring of 5-FU in metastatic colorectal cancer (CRC) have been reported, its utility among patients with early stage disease has not been reported.

Patients and Methods

We retrospectively examined the effect of 5-FU PK monitoring in 84 CRC patients (49 stage IV and 35 stage II/III) receiving mFOLFOX6 (modifiedFOLFOX6; modified 5-fluorouracil, leucovorin, oxaliplatin protocol) or mFOLFIRI (modified 5-fluorouracil, leucovorin, irinotecan protocol). Forty-six of the 84 patients received 5-FU doses based on BSA and 38 received doses that were adjusted with PK monitoring. 5-FU plasma levels were measured using a nanoparticle immunoassay method.

Results

5-fluorouracil PK monitoring significantly improved disease-free survival in stage II/III patients (P = .0429). There was also a trend towards improved progression-free survival among stage IV patients who had their 5-FU levels PK-monitored (P = .16). Moreover, 5-FU PK monitoring significantly reduced (P = .0437) and delayed (P = .0144) adverse effects in stage II/III patients. Toxicity occurred after the second 5-FU dose in the BSA group and after the sixth to seventh dose in the PK monitoring group. In stage IV patients, the onset of toxicities was also delayed with PK monitoring (P = .0605).

Conclusion

We provide evidence that PK monitoring of 5-FU is potentially beneficial for late stage and early stage CRC. These results contribute to the growing body of evidence regarding patient benefit when treatment decisions are based on the individual patient characteristics, in this case, a patients' 5-FU levels.