Open AccessA Phase I Trial of Oxaliplatin, Irinotecan, and S‐1 Combination Therapy ( OX‐IRIS ) as Chemotherapy for Unresectable Pancreatic Cancer ( HGCSG 1403)
Author(s) -
Kawamoto Yasuyuki,
Nakatsumi Hiroshi,
Harada Kazuaki,
Muranaka Tetsuhito,
Ishiguro Atsushi,
Kobayashi Yoshimitsu,
Hayashi Hideyuki,
Yuki Satoshi,
Sawada Kentaro,
Yagisawa Masataka,
Nakano Shintaro,
Sakamoto Naoya,
Komatsu Yoshito
Publication year - 2021
Publication title -
the oncologist
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.176
H-Index - 164
eISSN - 1549-490X
pISSN - 1083-7159
DOI - 10.1002/onco.13838
Subject(s) - medicine , irinotecan , oxaliplatin , gastroenterology , pancreatic cancer , gemcitabine , folfirinox , nausea , chemotherapy , oncology , cancer , colorectal cancer
Abstract Lessons Learned Because S‐1 is orally administered, OX‐IRIS does not necessitate the continuous infusion of 5‐FU and is more convenient. The recommended dose of OX‐IRIS was determined to be level −1 (oxaliplatin, 65 mg/m 2 ; irinotecan, 100 mg/m 2 ; S‐1, 80 mg/m 2 ), which has manageable safety and promising anticancer activities.Background OX‐IRIS is a new combination therapy of oxaliplatin, irinotecan, and S‐1 for unresectable pancreatic ductal adenocarcinoma (PDAC), which may be beneficial because S‐1 is administered orally and continuous infusion of 5‐fluorouracil (5‐FU) is not needed. Methods Patients who had not received prior therapy for unresectable PDAC were enrolled. Adenocarcinoma or adenosquamous histology was required. Oxaliplatin and irinotecan were administered on days 1 and 15; S‐1 was administered orally twice a day on days 1–14, followed by 14 days of rest (one cycle). Primary endpoints were dose‐limiting toxicity (DLT) and maximum tolerated dose (MTD). Secondary endpoints were safety, overall response rate (ORR), progression‐free survival (PFS), and overall survival (OS). Results In level 0 (oxaliplatin, 85 mg/m 2 ; irinotecan, 100 mg/m 2 ; S‐1, 80 mg/m 2 ), two of five patients experienced DLT. In level −1 (oxaliplatin, 65 mg/m 2 ; irinotecan, 100 mg/m 2 ; S‐1, 80 mg/m 2 ), DLT could not be evaluated in two of eight patients because one cycle was not completed; one of the remaining six patients experienced DLT. Anemia, thrombocytopenia, fatigue, nausea, anorexia, diarrhea, and peripheral sensory neuropathy were seen frequently in levels 0 and −1. ORR was 30% in levels 0 and −1. Median progression‐free survival and median overall survival were 4.1 months (95% confidence interval [CI], 0.0–8.9 months) and 13.7 months (95% CI, 4.8–22.6 months), respectively. Conclusion MTD of OX‐IRIS therapy was estimated to be level 0, and the recommended dose (RD) for future trial was level −1.