Influence of initial dose intensity on efficacy of FOLFIRINOX in patients with advanced pancreatic cancer
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Satoshi Kobayashi1, Makoto Ueno1, Katsuhiro Omae2, Hidekazu Kuramochi3, Masato Terao4, Nobumasa Mizuno5, Masato Ozaka6, Hideki Ueno7, Kazuhiro Uesugi8, Noritoshi Kobayashi9, Marina Kobayashi10, Akiko Todaka11 and Akira Fukutomi11
1Department of Gastroenterology, Hepatobiliary and Pancreatic Medical Oncology Division, Kanagawa Cancer Center, Yokohama, 241-0815, Japan
2Clinical Research Center, Clinical Research Promotion Unit, Shizuoka Cancer Center, Shuntogun, 411-8777, Japan
3Department of Medical Oncology, Tokyo Women’s Medical University Yachiyo Medical Center, Yachiyo, 276-8524, Japan
4Department of Medical Oncology, Fukuyama City Hospital, Fukuyama, 721-8511, Japan
5Department of Gastroenterology, Aichi Cancer Center Hospital, Nagoya, 464-8681, Japan
6Department of Gastroenterology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, 135-8550, Japan
7Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, 104-0045, Japan
8Department of Gastroenterology, National Hospital Organization Shikoku Cancer Center, Matsuyama, 791-0280, Japan
9Department of Oncology, Yokohama City University, Yokohama, 236-0004, Japan
10Clinical Trial Promotion Section, Shizuoka Industrial Foundation Pharma Valley Center, Shuntogun, 411-0934, Japan
11Department of Gastrointestinal Oncology, Shizuoka Cancer Center, Shuntogun, 411-8777, Japan
Satoshi Kobayashi, email: firstname.lastname@example.org
Keywords: irinotecan; fluorouracil; oxaliplatin; leucovorin; dose response relationship
Received: August 11, 2018 Accepted: January 17, 2019 Published: March 05, 2019
The combination of fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) is the standard of care for advanced pancreatic cancer, but causes hematological and gastrointestinal toxicities, leading to treatment delay and dose reduction; optimal modification based on toxicities is needed. Therefore, we evaluated the effect of initial relative dose intensity (RDI) on FOLFIRINOX efficacy by conducting a Japanese nationwide survey. We evaluated overall survival (OS) and progression-free survival (PFS) of patients administered two or more cycles of FOLFIRINOX, and determined RDIs for each drug within the first two cycles. RDI’s effect on efficacy was evaluated using a multivariate analysis with a Cox regression hazard model. Of 399 patients enrolled, 359 and 346 were evaluated for OS and PFS, respectively. Median RDI was 71.8%, 64.7%, 23.4%, and 76.9% for oxaliplatin, irinotecan, and bolus and continuous infusions of 5-FU, respectively. A high RDI for 5-FU bolus resulted in poor prognosis in terms of PFS (hazard ratio: 1.34; p = 0.022) and negatively correlated with objective response (coefficient: −0.70; p = 0.021), and a high RDI for CPT-11 positively correlated with objective response (coefficient: 1.02; p = 0.031). In conclusion, low and high RDIs for irinotecan and 5-FU bolus, respectively, resulted in poor FOLFIRINOX efficacy.
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