Safety and efficacy of S-IROX (S-1, irinotecan and oxaliplatin combination therapy) in patients with advanced pancreatic cancer: A multicenter phase 1b dose-escalation and dose-expansion clinical trial.


Journal

European journal of cancer (Oxford, England : 1990)
ISSN: 1879-0852
Titre abrégé: Eur J Cancer
Pays: England
ID NLM: 9005373

Informations de publication

Date de publication:
Oct 2022
Historique:
received: 06 03 2022
revised: 27 05 2022
accepted: 02 06 2022
pubmed: 16 8 2022
medline: 21 9 2022
entrez: 15 8 2022
Statut: ppublish

Résumé

This phase 1b trial evaluated the toxicity and efficacy of S-1, irinotecan, and oxaliplatin combination therapy (S-IROX) as first-line chemotherapy in patients with advanced pancreatic cancer (APC). Patients aged 20-75 years with APC and an Eastern Cooperative Oncology Group performance status of 0 or 1 were eligible to receive escalating doses of S-1 (60 or 80 mg m Approximately 47 patients were enrolled, of whom 45 were eligible for the analysis. The MTD was not determined, but the RD was determined to be dose level 1 based on a review of data from each level. Among the 45 patients, the ORR was 51.1% [95% confidence interval (CI), 35.8-66.3%]. The median progression-free survival and median overall survival was 6.9 months (95% CI, 5.1-8.8 months) and 15.8 months (95% CI, 9.8-20.8 months), respectively. Common adverse events included neutropenia, elevated liver enzyme levels, diarrhoea, and nausea. The S-IROX regimen showed promising efficacy with manageable toxicities in Japanese patients with APC. A randomised phase 2/3 trial comparing S-IROX, mFOLFIRINOX, and gemcitabine plus nab-paclitaxel is currently ongoing (jRCTs031190009).

Sections du résumé

BACKGROUND
This phase 1b trial evaluated the toxicity and efficacy of S-1, irinotecan, and oxaliplatin combination therapy (S-IROX) as first-line chemotherapy in patients with advanced pancreatic cancer (APC).
METHODS
Patients aged 20-75 years with APC and an Eastern Cooperative Oncology Group performance status of 0 or 1 were eligible to receive escalating doses of S-1 (60 or 80 mg m
RESULTS
Approximately 47 patients were enrolled, of whom 45 were eligible for the analysis. The MTD was not determined, but the RD was determined to be dose level 1 based on a review of data from each level. Among the 45 patients, the ORR was 51.1% [95% confidence interval (CI), 35.8-66.3%]. The median progression-free survival and median overall survival was 6.9 months (95% CI, 5.1-8.8 months) and 15.8 months (95% CI, 9.8-20.8 months), respectively. Common adverse events included neutropenia, elevated liver enzyme levels, diarrhoea, and nausea.
CONCLUSIONS
The S-IROX regimen showed promising efficacy with manageable toxicities in Japanese patients with APC. A randomised phase 2/3 trial comparing S-IROX, mFOLFIRINOX, and gemcitabine plus nab-paclitaxel is currently ongoing (jRCTs031190009).

Identifiants

pubmed: 35970035
pii: S0959-8049(22)00361-6
doi: 10.1016/j.ejca.2022.06.010
pii:
doi:

Substances chimiques

Organoplatinum Compounds 0
Oxaliplatin 04ZR38536J
Irinotecan 7673326042
Fluorouracil U3P01618RT
Camptothecin XT3Z54Z28A

Types de publication

Clinical Trial, Phase I Journal Article Multicenter Study Randomized Controlled Trial

Langues

eng

Sous-ensembles de citation

IM

Pagination

40-47

Informations de copyright

Copyright © 2022 Elsevier Ltd. All rights reserved.

Déclaration de conflit d'intérêts

Conflict of interest statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests. A.O. has received honoraria from Yakult and Taiho. N.O. has received honorarium from Taiho. F.M. has received research funding from Yakult, Taiho, and Daiichi Sankyo, honoraria from Yakult, Taiho, and Daiichi Sankyo. M.S. has received honorarium from Yakult. H.I. has received honorarium from Yakult. C.M. has received research funding from Yakult, Taiho, and Daiichi Sankyo, honoraria from Yakult and Taiho. M.O. has received honorarium from Yakult. M.I. has received research funding from Yakult, honoraria from Yakult and Taiho. J.F. has received research funding from Yakult, Taiho, and Daiichi Sankyo, honoraria from Yakult, Taiho, and Daiichi Sankyo. T.O. has received honoraria from Yakult, Taiho, and Daiichi Sankyo. All remaining authors have declared no conflicts of interest.

Auteurs

Akihiro Ohba (A)

Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, Japan.

Hideki Ueno (H)

Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, Japan. Electronic address: hiueno@ncc.go.jp.

Satoshi Shiba (S)

Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, Japan.

Naohiro Okano (N)

Department of Medical Oncology, Kyorin University Faculty of Medicine, Tokyo, Japan.

Takaaki Kobayashi (T)

Department of Medical Oncology, Kyorin University Faculty of Medicine, Tokyo, Japan.

Fumio Nagashima (F)

Department of Medical Oncology, Kyorin University Faculty of Medicine, Tokyo, Japan.

Naoki Sasahira (N)

Department of Gastroenterology, Cancer Institute Hospital, Tokyo, Japan.

Mitsuhito Sasaki (M)

Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Kashiwa, Japan.

Hiroshi Imaoka (H)

Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Kashiwa, Japan.

Yasunari Sakamoto (Y)

Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, Japan.

Shunsuke Kondo (S)

Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, Japan.

Chigusa Morizane (C)

Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, Japan.

Masato Ozaka (M)

Department of Gastroenterology, Cancer Institute Hospital, Tokyo, Japan.

Masafumi Ikeda (M)

Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, Kashiwa, Japan.

Junji Furuse (J)

Department of Medical Oncology, Kyorin University Faculty of Medicine, Tokyo, Japan.

Takuji Okusaka (T)

Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, Japan.

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Classifications MeSH