A phase I study of weekly docetaxel, 24-hour infusion of high-dose fluorouracil/leucovorin and cisplatin in patients with advanced gastric cancer

Li Tzong Chen, Tsang Wu Liu, Chew Wun Wu, Tsai Rong Chung, Her Shyong Shiah, Chang Ming Jan, Jacqueline Ming Liu, Jacqueline Whang-Peng, Jang Yang Chang

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Objectives: To determine the maximum-tolerated dose (MTD) and dose-limiting toxicity (DLT) of both docetaxel and 5-fluorouracil (5-FU) when administered weekly in a regimen of docetaxel, 5-FU/leucovorin and cisplatin (DFLP) for 2 consecutive weeks every 3 weeks. Patients and Methods: A total of 31 patients with chemonaive, advanced adenocarcinoma of the stomach were enrolled in the study. Cisplatin and leucovorin dosages were fixed throughout the study at 30 and 300 mg/m2, respectively. 5-FU dosage was fixed at 1,600 mg/m2 while docetaxel was evaluated at weekly 1-hour infusion dosages of 30, 40 and 50 mg/m2 to determine the MTD. Cisplatin, 5-FU and leucovorin were administered together as a 24-hour continuous infusion following docetaxel. Weekly 5-FU dosages of 1,600, 2,000 and 2,400 mg/m2 were then evaluated after setting the docetaxel dosage at the MTD. Results: A total of 95 chemotherapy cycles were administered, with a median of three cycles per patient. The MTD of docetaxel was defined at 40 mg/m2. At a docetaxel dosage of 50 mg/m2 per week, the dose-limiting events of grade 4 febrile neutropenia and grade 3 hypomagnesemia occurred. With fixation of docetaxel to 40 mg/m2, the DLT for 5-FU was found at 2,400 mg/m2 per week. This incurred grade 4 neutropenia such that the MTD of 5-FU was defined at 2,000 mg/m2. Grade 3/4 neutropenia occurred in 14 patients (45%), with 2 patients developing febrile neutropenia. Grade 2 and 3 hypomagnesemia and hypokalemia occurred in 9 (41%) and 4 (18%) patients, respectively, of the first 22 patients treated with a 24-hour infusion of cisplatin and 5-FU/leucovorin immediately following docetaxel. Following a change in the cisplatin administration schedule to a 3-hour infusion after 5-FU/leucovorin infusion, no such complications were observed in 9 subsequently treated patients. Grade 2 diarrhea was recorded in 11 patients (35%). Grade 2/3 asthenia occurred in 9 patients (30%), which resolved after correction of electrolyte disorders. Twenty-six patients were assessable for response analysis. There were 2 (7.8%) complete and 14 (53.8%) partial responses, with the overall response rate being 61.5% (95% confidence interval, 41.5-81.6%). Responses were observed at all dose levels. Conclusion: Two consecutive weeks of DFLP infusions every 3 weeks appear to be an active regimen with a tolerable toxicity profile in advanced gastric cancer. For further phase II studies, the recommended dose for this combination is 40 mg/m2 of docetaxel and 2,000 mg/m2 of 5-FU per week. Copyright

Original languageEnglish
Pages (from-to)239-247
Number of pages9
JournalOncology
Volume63
Issue number3
DOIs
Publication statusPublished - Dec 1 2002
Externally publishedYes

Fingerprint

docetaxel
Leucovorin
Fluorouracil
Cisplatin
Stomach Neoplasms
Maximum Tolerated Dose
Febrile Neutropenia
Neutropenia
Asthenia

Keywords

  • Cisplatin
  • Docetaxel
  • Gastric cancer
  • High-dose 5-fluorouracil
  • Leucovorin
  • Phase I

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

A phase I study of weekly docetaxel, 24-hour infusion of high-dose fluorouracil/leucovorin and cisplatin in patients with advanced gastric cancer. / Chen, Li Tzong; Liu, Tsang Wu; Wu, Chew Wun; Chung, Tsai Rong; Shiah, Her Shyong; Jan, Chang Ming; Ming Liu, Jacqueline; Whang-Peng, Jacqueline; Chang, Jang Yang.

In: Oncology, Vol. 63, No. 3, 01.12.2002, p. 239-247.

Research output: Contribution to journalArticle

Chen, Li Tzong ; Liu, Tsang Wu ; Wu, Chew Wun ; Chung, Tsai Rong ; Shiah, Her Shyong ; Jan, Chang Ming ; Ming Liu, Jacqueline ; Whang-Peng, Jacqueline ; Chang, Jang Yang. / A phase I study of weekly docetaxel, 24-hour infusion of high-dose fluorouracil/leucovorin and cisplatin in patients with advanced gastric cancer. In: Oncology. 2002 ; Vol. 63, No. 3. pp. 239-247.
@article{6778df158f40486eb5c3f479e48d32dc,
title = "A phase I study of weekly docetaxel, 24-hour infusion of high-dose fluorouracil/leucovorin and cisplatin in patients with advanced gastric cancer",
abstract = "Objectives: To determine the maximum-tolerated dose (MTD) and dose-limiting toxicity (DLT) of both docetaxel and 5-fluorouracil (5-FU) when administered weekly in a regimen of docetaxel, 5-FU/leucovorin and cisplatin (DFLP) for 2 consecutive weeks every 3 weeks. Patients and Methods: A total of 31 patients with chemonaive, advanced adenocarcinoma of the stomach were enrolled in the study. Cisplatin and leucovorin dosages were fixed throughout the study at 30 and 300 mg/m2, respectively. 5-FU dosage was fixed at 1,600 mg/m2 while docetaxel was evaluated at weekly 1-hour infusion dosages of 30, 40 and 50 mg/m2 to determine the MTD. Cisplatin, 5-FU and leucovorin were administered together as a 24-hour continuous infusion following docetaxel. Weekly 5-FU dosages of 1,600, 2,000 and 2,400 mg/m2 were then evaluated after setting the docetaxel dosage at the MTD. Results: A total of 95 chemotherapy cycles were administered, with a median of three cycles per patient. The MTD of docetaxel was defined at 40 mg/m2. At a docetaxel dosage of 50 mg/m2 per week, the dose-limiting events of grade 4 febrile neutropenia and grade 3 hypomagnesemia occurred. With fixation of docetaxel to 40 mg/m2, the DLT for 5-FU was found at 2,400 mg/m2 per week. This incurred grade 4 neutropenia such that the MTD of 5-FU was defined at 2,000 mg/m2. Grade 3/4 neutropenia occurred in 14 patients (45{\%}), with 2 patients developing febrile neutropenia. Grade 2 and 3 hypomagnesemia and hypokalemia occurred in 9 (41{\%}) and 4 (18{\%}) patients, respectively, of the first 22 patients treated with a 24-hour infusion of cisplatin and 5-FU/leucovorin immediately following docetaxel. Following a change in the cisplatin administration schedule to a 3-hour infusion after 5-FU/leucovorin infusion, no such complications were observed in 9 subsequently treated patients. Grade 2 diarrhea was recorded in 11 patients (35{\%}). Grade 2/3 asthenia occurred in 9 patients (30{\%}), which resolved after correction of electrolyte disorders. Twenty-six patients were assessable for response analysis. There were 2 (7.8{\%}) complete and 14 (53.8{\%}) partial responses, with the overall response rate being 61.5{\%} (95{\%} confidence interval, 41.5-81.6{\%}). Responses were observed at all dose levels. Conclusion: Two consecutive weeks of DFLP infusions every 3 weeks appear to be an active regimen with a tolerable toxicity profile in advanced gastric cancer. For further phase II studies, the recommended dose for this combination is 40 mg/m2 of docetaxel and 2,000 mg/m2 of 5-FU per week. Copyright",
keywords = "Cisplatin, Docetaxel, Gastric cancer, High-dose 5-fluorouracil, Leucovorin, Phase I",
author = "Chen, {Li Tzong} and Liu, {Tsang Wu} and Wu, {Chew Wun} and Chung, {Tsai Rong} and Shiah, {Her Shyong} and Jan, {Chang Ming} and {Ming Liu}, Jacqueline and Jacqueline Whang-Peng and Chang, {Jang Yang}",
year = "2002",
month = "12",
day = "1",
doi = "10.1159/000065471",
language = "English",
volume = "63",
pages = "239--247",
journal = "Oncology",
issn = "0030-2414",
publisher = "UBM Medica Healthcare Publications",
number = "3",

}

TY - JOUR

T1 - A phase I study of weekly docetaxel, 24-hour infusion of high-dose fluorouracil/leucovorin and cisplatin in patients with advanced gastric cancer

AU - Chen, Li Tzong

AU - Liu, Tsang Wu

AU - Wu, Chew Wun

AU - Chung, Tsai Rong

AU - Shiah, Her Shyong

AU - Jan, Chang Ming

AU - Ming Liu, Jacqueline

AU - Whang-Peng, Jacqueline

AU - Chang, Jang Yang

PY - 2002/12/1

Y1 - 2002/12/1

N2 - Objectives: To determine the maximum-tolerated dose (MTD) and dose-limiting toxicity (DLT) of both docetaxel and 5-fluorouracil (5-FU) when administered weekly in a regimen of docetaxel, 5-FU/leucovorin and cisplatin (DFLP) for 2 consecutive weeks every 3 weeks. Patients and Methods: A total of 31 patients with chemonaive, advanced adenocarcinoma of the stomach were enrolled in the study. Cisplatin and leucovorin dosages were fixed throughout the study at 30 and 300 mg/m2, respectively. 5-FU dosage was fixed at 1,600 mg/m2 while docetaxel was evaluated at weekly 1-hour infusion dosages of 30, 40 and 50 mg/m2 to determine the MTD. Cisplatin, 5-FU and leucovorin were administered together as a 24-hour continuous infusion following docetaxel. Weekly 5-FU dosages of 1,600, 2,000 and 2,400 mg/m2 were then evaluated after setting the docetaxel dosage at the MTD. Results: A total of 95 chemotherapy cycles were administered, with a median of three cycles per patient. The MTD of docetaxel was defined at 40 mg/m2. At a docetaxel dosage of 50 mg/m2 per week, the dose-limiting events of grade 4 febrile neutropenia and grade 3 hypomagnesemia occurred. With fixation of docetaxel to 40 mg/m2, the DLT for 5-FU was found at 2,400 mg/m2 per week. This incurred grade 4 neutropenia such that the MTD of 5-FU was defined at 2,000 mg/m2. Grade 3/4 neutropenia occurred in 14 patients (45%), with 2 patients developing febrile neutropenia. Grade 2 and 3 hypomagnesemia and hypokalemia occurred in 9 (41%) and 4 (18%) patients, respectively, of the first 22 patients treated with a 24-hour infusion of cisplatin and 5-FU/leucovorin immediately following docetaxel. Following a change in the cisplatin administration schedule to a 3-hour infusion after 5-FU/leucovorin infusion, no such complications were observed in 9 subsequently treated patients. Grade 2 diarrhea was recorded in 11 patients (35%). Grade 2/3 asthenia occurred in 9 patients (30%), which resolved after correction of electrolyte disorders. Twenty-six patients were assessable for response analysis. There were 2 (7.8%) complete and 14 (53.8%) partial responses, with the overall response rate being 61.5% (95% confidence interval, 41.5-81.6%). Responses were observed at all dose levels. Conclusion: Two consecutive weeks of DFLP infusions every 3 weeks appear to be an active regimen with a tolerable toxicity profile in advanced gastric cancer. For further phase II studies, the recommended dose for this combination is 40 mg/m2 of docetaxel and 2,000 mg/m2 of 5-FU per week. Copyright

AB - Objectives: To determine the maximum-tolerated dose (MTD) and dose-limiting toxicity (DLT) of both docetaxel and 5-fluorouracil (5-FU) when administered weekly in a regimen of docetaxel, 5-FU/leucovorin and cisplatin (DFLP) for 2 consecutive weeks every 3 weeks. Patients and Methods: A total of 31 patients with chemonaive, advanced adenocarcinoma of the stomach were enrolled in the study. Cisplatin and leucovorin dosages were fixed throughout the study at 30 and 300 mg/m2, respectively. 5-FU dosage was fixed at 1,600 mg/m2 while docetaxel was evaluated at weekly 1-hour infusion dosages of 30, 40 and 50 mg/m2 to determine the MTD. Cisplatin, 5-FU and leucovorin were administered together as a 24-hour continuous infusion following docetaxel. Weekly 5-FU dosages of 1,600, 2,000 and 2,400 mg/m2 were then evaluated after setting the docetaxel dosage at the MTD. Results: A total of 95 chemotherapy cycles were administered, with a median of three cycles per patient. The MTD of docetaxel was defined at 40 mg/m2. At a docetaxel dosage of 50 mg/m2 per week, the dose-limiting events of grade 4 febrile neutropenia and grade 3 hypomagnesemia occurred. With fixation of docetaxel to 40 mg/m2, the DLT for 5-FU was found at 2,400 mg/m2 per week. This incurred grade 4 neutropenia such that the MTD of 5-FU was defined at 2,000 mg/m2. Grade 3/4 neutropenia occurred in 14 patients (45%), with 2 patients developing febrile neutropenia. Grade 2 and 3 hypomagnesemia and hypokalemia occurred in 9 (41%) and 4 (18%) patients, respectively, of the first 22 patients treated with a 24-hour infusion of cisplatin and 5-FU/leucovorin immediately following docetaxel. Following a change in the cisplatin administration schedule to a 3-hour infusion after 5-FU/leucovorin infusion, no such complications were observed in 9 subsequently treated patients. Grade 2 diarrhea was recorded in 11 patients (35%). Grade 2/3 asthenia occurred in 9 patients (30%), which resolved after correction of electrolyte disorders. Twenty-six patients were assessable for response analysis. There were 2 (7.8%) complete and 14 (53.8%) partial responses, with the overall response rate being 61.5% (95% confidence interval, 41.5-81.6%). Responses were observed at all dose levels. Conclusion: Two consecutive weeks of DFLP infusions every 3 weeks appear to be an active regimen with a tolerable toxicity profile in advanced gastric cancer. For further phase II studies, the recommended dose for this combination is 40 mg/m2 of docetaxel and 2,000 mg/m2 of 5-FU per week. Copyright

KW - Cisplatin

KW - Docetaxel

KW - Gastric cancer

KW - High-dose 5-fluorouracil

KW - Leucovorin

KW - Phase I

UR - http://www.scopus.com/inward/record.url?scp=0036969979&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036969979&partnerID=8YFLogxK

U2 - 10.1159/000065471

DO - 10.1159/000065471

M3 - Article

C2 - 12381903

AN - SCOPUS:0036969979

VL - 63

SP - 239

EP - 247

JO - Oncology

JF - Oncology

SN - 0030-2414

IS - 3

ER -