Phase I/II study of oxaliplatin with weekly bolus fluorouracil and high-dose leucovorin (ROX) As first-line therapy for patients with colorectal cancer

Yasuhide Yamada, Atsushi Ohtsu, Narikazu Boku, Yoshinori Miyata, Yasuhiro Shimada, Toshihiko Doi, Kei Muro, Manabu Muto, Tetsuya Hamaguchi, Kiyomi Mera, Tomonori Yano, Yusuke Tanigawara, Kuniaki Shirao

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Background: Infusional fluorouracil (5-FU) and leucovorin (LV) with oxaliplatin is one of the current standard regimens for the treatment of patients with metastatic colorectal cancer. Weekly bolus 5-FU with high-dose LV (Roswell Park Memorial Institute Regimen: RPMI) is the most commonly used regimen in Japan. The objectives of this study were to determine the recommended dose (RD) of RPMI combined with oxaliplatin and to evaluate the toxicity and efficacy at the RD. Methods: The subjects were 18 patients with metastatic colorectal cancer. Oxaliplatin (85 mg/m2) was given intravenously over 2 h on days 1 and 15 with l-LV (250 mg/m2) given intravenously over 2 h and 5-FU as an intravenous bolus on days 1, 8, and 15. This treatment was repeated every 4 weeks. The dose of 5-FU was escalated from 400 mg/m2 (level 1) to 500 mg/m2 (level 2). Results: A total of 14 patients received level 1, and 4 received level 2. Three of the patients had dose-limiting toxicity (DLT) in cycle 1 of level 2 (grade 3 thrombocytopenia, grade 4 neutropenia and grade 2 neutropenia in one patient each), requiring that treatment was delayed for longer than 7 days. None of the 14 patients given level 1 had DLT or grade 3 or 4 gastrointestinal toxicity. Sensory neuropathy occurred in all patients. Objective response rates were 61% in the 18 patients studied and 64% at level 1. The median time to progression was 171 days, and the median overall survival time was 603 days in the 18 patients studied. Conclusions: Oxaliplatin (85 mg/m2) with weekly bol us 5-FU (400 mg/m2) and high-dose l-LV (250 mg/m2) is recommended for further phase III studies in patients with metastatic colorectal cancer.

Original languageEnglish
Pages (from-to)218-223
Number of pages6
JournalJapanese Journal of Clinical Oncology
Volume36
Issue number4
DOIs
Publication statusPublished - 2006 Apr

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oxaliplatin
Leucovorin
Fluorouracil
Colorectal Neoplasms
Therapeutics
Neutropenia

Keywords

  • Bolus 5-fluorouracil
  • Colorectal cancer
  • Leucovorin
  • Oxaliplatin
  • RPMI

ASJC Scopus subject areas

  • Oncology

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Phase I/II study of oxaliplatin with weekly bolus fluorouracil and high-dose leucovorin (ROX) As first-line therapy for patients with colorectal cancer. / Yamada, Yasuhide; Ohtsu, Atsushi; Boku, Narikazu; Miyata, Yoshinori; Shimada, Yasuhiro; Doi, Toshihiko; Muro, Kei; Muto, Manabu; Hamaguchi, Tetsuya; Mera, Kiyomi; Yano, Tomonori; Tanigawara, Yusuke; Shirao, Kuniaki.

In: Japanese Journal of Clinical Oncology, Vol. 36, No. 4, 04.2006, p. 218-223.

Research output: Contribution to journalArticle

Yamada, Y, Ohtsu, A, Boku, N, Miyata, Y, Shimada, Y, Doi, T, Muro, K, Muto, M, Hamaguchi, T, Mera, K, Yano, T, Tanigawara, Y & Shirao, K 2006, 'Phase I/II study of oxaliplatin with weekly bolus fluorouracil and high-dose leucovorin (ROX) As first-line therapy for patients with colorectal cancer', Japanese Journal of Clinical Oncology, vol. 36, no. 4, pp. 218-223. https://doi.org/10.1093/jjco/hyl020
Yamada, Yasuhide ; Ohtsu, Atsushi ; Boku, Narikazu ; Miyata, Yoshinori ; Shimada, Yasuhiro ; Doi, Toshihiko ; Muro, Kei ; Muto, Manabu ; Hamaguchi, Tetsuya ; Mera, Kiyomi ; Yano, Tomonori ; Tanigawara, Yusuke ; Shirao, Kuniaki. / Phase I/II study of oxaliplatin with weekly bolus fluorouracil and high-dose leucovorin (ROX) As first-line therapy for patients with colorectal cancer. In: Japanese Journal of Clinical Oncology. 2006 ; Vol. 36, No. 4. pp. 218-223.
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title = "Phase I/II study of oxaliplatin with weekly bolus fluorouracil and high-dose leucovorin (ROX) As first-line therapy for patients with colorectal cancer",
abstract = "Background: Infusional fluorouracil (5-FU) and leucovorin (LV) with oxaliplatin is one of the current standard regimens for the treatment of patients with metastatic colorectal cancer. Weekly bolus 5-FU with high-dose LV (Roswell Park Memorial Institute Regimen: RPMI) is the most commonly used regimen in Japan. The objectives of this study were to determine the recommended dose (RD) of RPMI combined with oxaliplatin and to evaluate the toxicity and efficacy at the RD. Methods: The subjects were 18 patients with metastatic colorectal cancer. Oxaliplatin (85 mg/m2) was given intravenously over 2 h on days 1 and 15 with l-LV (250 mg/m2) given intravenously over 2 h and 5-FU as an intravenous bolus on days 1, 8, and 15. This treatment was repeated every 4 weeks. The dose of 5-FU was escalated from 400 mg/m2 (level 1) to 500 mg/m2 (level 2). Results: A total of 14 patients received level 1, and 4 received level 2. Three of the patients had dose-limiting toxicity (DLT) in cycle 1 of level 2 (grade 3 thrombocytopenia, grade 4 neutropenia and grade 2 neutropenia in one patient each), requiring that treatment was delayed for longer than 7 days. None of the 14 patients given level 1 had DLT or grade 3 or 4 gastrointestinal toxicity. Sensory neuropathy occurred in all patients. Objective response rates were 61{\%} in the 18 patients studied and 64{\%} at level 1. The median time to progression was 171 days, and the median overall survival time was 603 days in the 18 patients studied. Conclusions: Oxaliplatin (85 mg/m2) with weekly bol us 5-FU (400 mg/m2) and high-dose l-LV (250 mg/m2) is recommended for further phase III studies in patients with metastatic colorectal cancer.",
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author = "Yasuhide Yamada and Atsushi Ohtsu and Narikazu Boku and Yoshinori Miyata and Yasuhiro Shimada and Toshihiko Doi and Kei Muro and Manabu Muto and Tetsuya Hamaguchi and Kiyomi Mera and Tomonori Yano and Yusuke Tanigawara and Kuniaki Shirao",
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T1 - Phase I/II study of oxaliplatin with weekly bolus fluorouracil and high-dose leucovorin (ROX) As first-line therapy for patients with colorectal cancer

AU - Yamada, Yasuhide

AU - Ohtsu, Atsushi

AU - Boku, Narikazu

AU - Miyata, Yoshinori

AU - Shimada, Yasuhiro

AU - Doi, Toshihiko

AU - Muro, Kei

AU - Muto, Manabu

AU - Hamaguchi, Tetsuya

AU - Mera, Kiyomi

AU - Yano, Tomonori

AU - Tanigawara, Yusuke

AU - Shirao, Kuniaki

PY - 2006/4

Y1 - 2006/4

N2 - Background: Infusional fluorouracil (5-FU) and leucovorin (LV) with oxaliplatin is one of the current standard regimens for the treatment of patients with metastatic colorectal cancer. Weekly bolus 5-FU with high-dose LV (Roswell Park Memorial Institute Regimen: RPMI) is the most commonly used regimen in Japan. The objectives of this study were to determine the recommended dose (RD) of RPMI combined with oxaliplatin and to evaluate the toxicity and efficacy at the RD. Methods: The subjects were 18 patients with metastatic colorectal cancer. Oxaliplatin (85 mg/m2) was given intravenously over 2 h on days 1 and 15 with l-LV (250 mg/m2) given intravenously over 2 h and 5-FU as an intravenous bolus on days 1, 8, and 15. This treatment was repeated every 4 weeks. The dose of 5-FU was escalated from 400 mg/m2 (level 1) to 500 mg/m2 (level 2). Results: A total of 14 patients received level 1, and 4 received level 2. Three of the patients had dose-limiting toxicity (DLT) in cycle 1 of level 2 (grade 3 thrombocytopenia, grade 4 neutropenia and grade 2 neutropenia in one patient each), requiring that treatment was delayed for longer than 7 days. None of the 14 patients given level 1 had DLT or grade 3 or 4 gastrointestinal toxicity. Sensory neuropathy occurred in all patients. Objective response rates were 61% in the 18 patients studied and 64% at level 1. The median time to progression was 171 days, and the median overall survival time was 603 days in the 18 patients studied. Conclusions: Oxaliplatin (85 mg/m2) with weekly bol us 5-FU (400 mg/m2) and high-dose l-LV (250 mg/m2) is recommended for further phase III studies in patients with metastatic colorectal cancer.

AB - Background: Infusional fluorouracil (5-FU) and leucovorin (LV) with oxaliplatin is one of the current standard regimens for the treatment of patients with metastatic colorectal cancer. Weekly bolus 5-FU with high-dose LV (Roswell Park Memorial Institute Regimen: RPMI) is the most commonly used regimen in Japan. The objectives of this study were to determine the recommended dose (RD) of RPMI combined with oxaliplatin and to evaluate the toxicity and efficacy at the RD. Methods: The subjects were 18 patients with metastatic colorectal cancer. Oxaliplatin (85 mg/m2) was given intravenously over 2 h on days 1 and 15 with l-LV (250 mg/m2) given intravenously over 2 h and 5-FU as an intravenous bolus on days 1, 8, and 15. This treatment was repeated every 4 weeks. The dose of 5-FU was escalated from 400 mg/m2 (level 1) to 500 mg/m2 (level 2). Results: A total of 14 patients received level 1, and 4 received level 2. Three of the patients had dose-limiting toxicity (DLT) in cycle 1 of level 2 (grade 3 thrombocytopenia, grade 4 neutropenia and grade 2 neutropenia in one patient each), requiring that treatment was delayed for longer than 7 days. None of the 14 patients given level 1 had DLT or grade 3 or 4 gastrointestinal toxicity. Sensory neuropathy occurred in all patients. Objective response rates were 61% in the 18 patients studied and 64% at level 1. The median time to progression was 171 days, and the median overall survival time was 603 days in the 18 patients studied. Conclusions: Oxaliplatin (85 mg/m2) with weekly bol us 5-FU (400 mg/m2) and high-dose l-LV (250 mg/m2) is recommended for further phase III studies in patients with metastatic colorectal cancer.

KW - Bolus 5-fluorouracil

KW - Colorectal cancer

KW - Leucovorin

KW - Oxaliplatin

KW - RPMI

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