Phase I-II trial of weekly gemcitabine plus high-dose 5-fluorouracil and leucovorin in advanced pancreatic cancer

Her Shyong Shiah, Ann Lii Cheng, Chiun Hsu, Chih Hung Hsu, Tsang Wu Liu, Jang Yang Chang, Chang Ming Jan, Yee Chao, Wei Lan Yu, Tsai Rong Chuang, Jacqueline Whang-Peng, Li Tzong Chen

Research output: Contribution to journalArticle

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Abstract

Background: Pancreatic cancer is a dismal disease. Few drugs, including gemcitabine and 5-fluorouracil (5-FU), have notable antitumor effects against advanced pancreatic cancer. The purpose of the present study was to determine the maximum tolerated dose (MTD) of 5-FU and the efficacy and toxicity profile of weekly gemcitabine plus infusional 5-FU/leucovorin in advanced pancreatic cancer. Methods: Patients with histo-/cytologically confirmed, advanced pancreatic cancer were eligible. Treatment consisted of a 30-min infusion of gemcitabine (800 mg/m2), followed by a 24-h infusion of 5-FU and leucovorin (300 mg/m2) at day 1, day 8 and day 15 every 28 days, and was termed the GemFL24 regimen. The dose of 5-FU was escalated from 1600, 2000, to 2600 mg/m2 in the phase I study, and fixed MTD for subsequent enrolled patients. Results: Eighteen patients were enrolled in the phase I study, and 24 in phase II. The MTD of 5-FU was 2000 mg/m2, with major dose-limiting toxicities being febrile neutropenia and delayed recovery from neutropenia. The dose intensity of gemcitabine of the 35 patients with 5-FU dosage set at MTD was 593 mg/m2 per week. In the entire series of 42 patients, myelosuppression was the main toxicity, with grade 3 neutropenia in eight patients, and grade 3/4 thrombocytopenia in six. On an intention-to-treat analysis, the overall and clinical benefit response rates were 22% and 46%, respectively; with median progression-free and overall survival of 4.1 and 6.9 months, respectively. Conclusions: The GemFL 24 regimen is a feasible and moderately active treatment with manageable toxicities for advanced pancreatic cancer, and could be a basis for further combination with other anticancer drugs.

Original languageEnglish
Pages (from-to)531-536
Number of pages6
JournalJournal of Gastroenterology and Hepatology (Australia)
Volume21
Issue number3
DOIs
Publication statusPublished - Jan 1 2006
Externally publishedYes

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gemcitabine
Leucovorin
Pancreatic Neoplasms
Fluorouracil
Maximum Tolerated Dose
Neutropenia
Febrile Neutropenia
Intention to Treat Analysis
Pharmaceutical Preparations
Disease-Free Survival

Keywords

  • 5-fluorouracil
  • Gemcitabine
  • High dose
  • Leucovorin
  • Pancreatic cancer

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

Cite this

Phase I-II trial of weekly gemcitabine plus high-dose 5-fluorouracil and leucovorin in advanced pancreatic cancer. / Shiah, Her Shyong; Cheng, Ann Lii; Hsu, Chiun; Hsu, Chih Hung; Liu, Tsang Wu; Chang, Jang Yang; Jan, Chang Ming; Chao, Yee; Yu, Wei Lan; Chuang, Tsai Rong; Whang-Peng, Jacqueline; Chen, Li Tzong.

In: Journal of Gastroenterology and Hepatology (Australia), Vol. 21, No. 3, 01.01.2006, p. 531-536.

Research output: Contribution to journalArticle

Shiah, Her Shyong ; Cheng, Ann Lii ; Hsu, Chiun ; Hsu, Chih Hung ; Liu, Tsang Wu ; Chang, Jang Yang ; Jan, Chang Ming ; Chao, Yee ; Yu, Wei Lan ; Chuang, Tsai Rong ; Whang-Peng, Jacqueline ; Chen, Li Tzong. / Phase I-II trial of weekly gemcitabine plus high-dose 5-fluorouracil and leucovorin in advanced pancreatic cancer. In: Journal of Gastroenterology and Hepatology (Australia). 2006 ; Vol. 21, No. 3. pp. 531-536.
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AU - Shiah, Her Shyong

AU - Cheng, Ann Lii

AU - Hsu, Chiun

AU - Hsu, Chih Hung

AU - Liu, Tsang Wu

AU - Chang, Jang Yang

AU - Jan, Chang Ming

AU - Chao, Yee

AU - Yu, Wei Lan

AU - Chuang, Tsai Rong

AU - Whang-Peng, Jacqueline

AU - Chen, Li Tzong

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AB - Background: Pancreatic cancer is a dismal disease. Few drugs, including gemcitabine and 5-fluorouracil (5-FU), have notable antitumor effects against advanced pancreatic cancer. The purpose of the present study was to determine the maximum tolerated dose (MTD) of 5-FU and the efficacy and toxicity profile of weekly gemcitabine plus infusional 5-FU/leucovorin in advanced pancreatic cancer. Methods: Patients with histo-/cytologically confirmed, advanced pancreatic cancer were eligible. Treatment consisted of a 30-min infusion of gemcitabine (800 mg/m2), followed by a 24-h infusion of 5-FU and leucovorin (300 mg/m2) at day 1, day 8 and day 15 every 28 days, and was termed the GemFL24 regimen. The dose of 5-FU was escalated from 1600, 2000, to 2600 mg/m2 in the phase I study, and fixed MTD for subsequent enrolled patients. Results: Eighteen patients were enrolled in the phase I study, and 24 in phase II. The MTD of 5-FU was 2000 mg/m2, with major dose-limiting toxicities being febrile neutropenia and delayed recovery from neutropenia. The dose intensity of gemcitabine of the 35 patients with 5-FU dosage set at MTD was 593 mg/m2 per week. In the entire series of 42 patients, myelosuppression was the main toxicity, with grade 3 neutropenia in eight patients, and grade 3/4 thrombocytopenia in six. On an intention-to-treat analysis, the overall and clinical benefit response rates were 22% and 46%, respectively; with median progression-free and overall survival of 4.1 and 6.9 months, respectively. Conclusions: The GemFL 24 regimen is a feasible and moderately active treatment with manageable toxicities for advanced pancreatic cancer, and could be a basis for further combination with other anticancer drugs.

KW - 5-fluorouracil

KW - Gemcitabine

KW - High dose

KW - Leucovorin

KW - Pancreatic cancer

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