A multicenter, phase I/II trial of biweekly S-1, leucovorin, oxaliplatin and gemcitabine in metastatic pancreatic adenocarcinoma–TCOG T1211 study

Nai Jung Chiang, Kelvin K. Tsai, Chin Fu Hsiao, Shih Hung Yang, Hui Hua Hsiao, Wen Chi Shen, Chiun Hsu, Yu Lin Lin, Jen Shi Chen, Yan Shen Shan, Li Tzong Chen

Research output: Contribution to journalArticle

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).

Original languageEnglish
Pages (from-to)123-130
Number of pages8
JournalEuropean Journal of Cancer
Volume124
DOIs
Publication statusPublished - 2020 Jan

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oxaliplatin
gemcitabine
Leucovorin
Adenocarcinoma
irinotecan
Maximum Tolerated Dose
Confidence Intervals
Feasibility Studies
Neutropenia
Fluorouracil
Disease-Free Survival

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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Chiang, Nai Jung ; Tsai, Kelvin K. ; Hsiao, Chin Fu ; Yang, Shih Hung ; Hsiao, Hui Hua ; Shen, Wen Chi ; Hsu, Chiun ; Lin, Yu Lin ; Chen, Jen Shi ; Shan, Yan Shen ; Chen, Li Tzong. / A multicenter, phase I/II trial of biweekly S-1, leucovorin, oxaliplatin and gemcitabine in metastatic pancreatic adenocarcinoma–TCOG T1211 study. In: European Journal of Cancer. 2020 ; Vol. 124. pp. 123-130.
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title = "A multicenter, phase I/II trial of biweekly S-1, leucovorin, oxaliplatin and gemcitabine in metastatic pancreatic adenocarcinoma–TCOG T1211 study",
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).",
author = "Chiang, {Nai Jung} and Tsai, {Kelvin K.} and Hsiao, {Chin Fu} and Yang, {Shih Hung} and Hsiao, {Hui Hua} and Shen, {Wen Chi} and Chiun Hsu and Lin, {Yu Lin} and Chen, {Jen Shi} and Shan, {Yan Shen} and Chen, {Li Tzong}",
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A multicenter, phase I/II trial of biweekly S-1, leucovorin, oxaliplatin and gemcitabine in metastatic pancreatic adenocarcinoma–TCOG T1211 study. / Chiang, Nai Jung; Tsai, Kelvin K.; Hsiao, Chin Fu; Yang, Shih Hung; Hsiao, Hui Hua; Shen, Wen Chi; Hsu, Chiun; Lin, Yu Lin; Chen, Jen Shi; Shan, Yan Shen; Chen, Li Tzong.

In: European Journal of Cancer, Vol. 124, 01.2020, p. 123-130.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A multicenter, phase I/II trial of biweekly S-1, leucovorin, oxaliplatin and gemcitabine in metastatic pancreatic adenocarcinoma–TCOG T1211 study

AU - Chiang, Nai Jung

AU - Tsai, Kelvin K.

AU - Hsiao, Chin Fu

AU - Yang, Shih Hung

AU - Hsiao, Hui Hua

AU - Shen, Wen Chi

AU - Hsu, Chiun

AU - Lin, Yu Lin

AU - Chen, Jen Shi

AU - Shan, Yan Shen

AU - Chen, Li Tzong

PY - 2020/1

Y1 - 2020/1

N2 - 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).

AB - 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).

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