5-FU, Irinotecan, Nab-Paclitaxel in Gastrointestinal Cancers—Letter Osamu Maeda, Tomoya Shimokata, and Yuichi Ando

CLINICAL CANCER RESEARCH | LETTER TO THE EDITOR

In the safety and tolerability study of a novel FOLFIRABRAX 130 mg/m2 (2, 3). The irinotecan doses used in the FOLFIRABRAX regimen in patients with gastrointestinal cancers by Joshi and collea- regimen are clearly too low. It is of our opinion that the standard one- gues (1), the irinotecan doses were determined by UGT1A1 genotypes: size dose of biweekly irinotecan, regardless of UGT1A1 genotype, 180, 135, and 90 for wild-type (Ã1/Ã1), heterozygous (Ã1/Ã28), and should be tailored to at least 300 mg/m2 or more for wild-type and homozygous (Ã28/Ã28) patients, respectively. The authors reported heterozygous patients, and 120–150 mg/m2 would be appropriate for that this regimen with genotype-guided dosing of irinotecan was homozygous patients, which corresponds to a 1 or 2 dose level tolerable based on the result that dose-limiting toxicities occurred in reduction compared with that in the package insert of the drug. This 5 of 23 (22%) wild-type, 1 of 19 (5%) heterozygous, and 0 of 7 dosing is consistent with the finding of the previous pharmacokinetic homozygous patients. However, their conclusion truly concerns us study that the exposure to the active metabolite SN-38 is approxi- that the regimen is not strong enough for patients with any of the mately double in homozygous patients compared with patients with genotypes. According to the genotype-guided dose-finding studies of the other genotypes. The real benefit of genotype-guided dosing of irinotecan in analogous FOLFIRI regimens, the maximum-tolerated or irinotecan is not only to avoid unnecessary toxicity of irinotecan in recommended doses for wild-type and heterozygous patients homozygous patients by reducing the dose but also to enhance the were more than 300 mg/m2 and that for homozygous patients was therapeutic efficacy in wild-type and heterozygous patients by increas- ing the dose to the optimal one.

Disclosure of Potential Conflicts of Interest Department of Clinical Oncology and Chemotherapy, Nagoya University O. Maeda reports receiving speakers bureau honoraria from Yakult Honsha Co., Hospital, Nagoya, Japan. Ltd. and Taiho Pharmaceutical Co., Ltd. Y. Ando reports receiving commercial Corresponding Author: Osamu Maeda, Nagoya University Hospital, Nagoya research grants from Yakult Honsha, Mochida Pharmaceutical, Taiho Pharmaceu- 466-8560, Japan. Phone/Fax: 815-2744-1903; E-mail: tical, Daiichi Sankyo, and Nippon Kayaku, and reports receiving speakers bureau [email protected] honoraria from Yakult Honsha, Taiho Pharmaceutical, Daiichi Sankyo, and Sawai Pharmaceutical. No potential conflicts of interest were disclosed by the other author. Clin Cancer Res 2020;26:3889 doi: 10.1158/1078-0432.CCR-20-0156 Received January 20, 2020; revised April 4, 2020; accepted April 20, 2020; Ó2020 American Association for Cancer Research. published first July 15, 2020.

References 1. Joshi SS, Catenacci DVT, Karrison TG, Peterson JD, Zalupski MM, Sehdev A, et al. fluorouracil/leucovorin in patients with metastatic colorectal cancer. J Clin Oncol Clinical assessment of 5-fluorouracil/leucovorin, nab-paclitaxel, and irinotecan 2010;28:866–71. (FOLFIRABRAX) in untreated patients with gastrointestinal cancer using. 3. Marcuello E, Paez D, Pare L, Salazar J, Sebio A, del Rio E, et al. A genotype-directed Clin Cancer Res 2020;26:18–24. phase I-IV dose-finding study of irinotecan in combination with fluorouracil/ 2. Toffoli G, Cecchin E, Gasparini G, D'Andrea M, Azzarello G, Basso U, et al. leucovorin as first-line treatment in advanced colorectal cancer. Br J Cancer 2011; Genotype-driven phase I study of irinotecan administered in combination with 105:53–7.

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Osamu Maeda, Tomoya Shimokata and Yuichi Ando

Clin Cancer Res 2020;26:3889.

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