A multicenter, phase I/II trial of biweekly S-1, leucovorin, oxaliplatin and gemcitabine in metastatic pancreatic adenocarcinoma–TCOG T1211 study
Journal
European Journal of Cancer
Journal Volume
124
Pages
123-130
Date Issued
2020
Author(s)
Chiang N.-J.
Tsai K.K.
Hsiao C.-F.
Hsiao H.-H.
Shen W.-C.
Lin Y.-L.
Chen J.-S.
Shan Y.-S.
Chen L.-T.
Abstract
Background: This phase I/II study evaluated the feasibility and efficacy of S-1, leucovorin, oxaliplatin and gemcitabine (SLOG), a triplet regimen, for treating patients with metastatic pancreatic ductal adenocarcinoma (PDAC). Methods: Patients with chemo-naive, metastatic PDAC were eligible to receive fixed-rate infusion (10 mg/m2/min) of gemcitabine of 800 mg/m2 followed by 85 mg/m oxaliplatin of 85 mg/m2 on day 1 plus oral S-1 and leucovorin (20 mg/m2) twice daily from days 1 to 7 in a 2-week cycle. The dose of S-1 would be escalated from 20, 30, 35 to 40 mg/m2 in a 3 + 3 designed phase I part to determine the maximum tolerated dose (MTD) for phase II study, in which the primary end-point was objective response rate (ORR). The recommended dose of S-1 was from phase I. This trial is registered at ClinicalTrials.gov: NCT01415713. Results: Seventy-three patients were enrolled. In the phase I study (n = 19), the MTD of S-1 was 35 mg/m2 twice daily. Of 54 patients in phase II, the ORR was 40.7% (95% confidence interval [CI], 28%–55%). The median progression-free survival and overall survival were 7.6 (95% CI, 5.6–11.0) and 11.4 (95% CI, 8.1–16.3) months, respectively. The most common grade III/IV adverse event was neutropenia (40.7%). Twenty-four percent of patients had SLOG treatment for more than 1 year. The mean relative dose intensities of gemcitabine, oxaliplatin, and S-1 were 92%, 92% and 89%, respectively. Conclusion: Biweekly SLOG is a feasible regimen with promising activity and safety profiles. A randomised study comparing SLOG versus modified folinic acid, fluorouracil, irinotecan, and oxaliplatin (FOLFIRINOX) in advanced PDAC is ongoing (ClinicalTrials.gov: NCT03443492). ? 2019 Elsevier Ltd
SDGs
Other Subjects
alanine aminotransferase; aspartate aminotransferase; CA 19-9 antigen; cisplatin; erlotinib; fluorouracil; folinic acid; gamma glutamyltransferase; gemcitabine; gimeracil plus oteracil potassium plus tegafur; irinotecan; oxaliplatin; paclitaxel; antineoplastic agent; deoxycytidine; folinic acid; gemcitabine; oteracil; oxaliplatin; S 1 (combination); tegafur; adult; aged; alanine aminotransferase blood level; allergy; alopecia; anemia; anorexia; Article; aspartate aminotransferase blood level; cancer combination chemotherapy; cancer patient; diarrhea; drug dose increase; drug efficacy; drug megadose; drug safety; drug withdrawal; fatigue; febrile neutropenia; female; gamma glutamyl transferase blood level; human; hyperpigmentation; leukopenia; major clinical study; male; maximum tolerated dose; metastasis; multicenter study; multiple cycle treatment; nausea; neutropenia; oral mucositis; overall survival; pancreas adenocarcinoma; peripheral neuropathy; phase 1 clinical trial; phase 2 clinical trial; priority journal; progression free survival; pruritus; rash; sensory neuropathy; sepsis; side effect; thrombocytopenia; treatment duration; vomiting; adenocarcinoma; clinical trial; drug combination; metastasis; middle aged; pancreas carcinoma; pancreas tumor; pathology; Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Pancreatic Ductal; Deoxycytidine; Drug Combinations; Female; Humans; Leucovorin; Male; Middle Aged; Neoplasm Metastasis; Oxaliplatin; Oxonic Acid; Pancreatic Neoplasms; Tegafur
Publisher
Elsevier Ltd
Type
journal article