Phase i study of bevacizumab combined with irinotecan and S-1 as second-line chemotherapy in patients with advanced colorectal cancer

Hitoshi Kusaba, Taito Esaki, Junji Kishimoto, Keita Uchino, Shuji Arita, Hozumi Kumagai, Kenji Mitsugi, Koichi Akashi, Eishi Baba

Research output: Contribution to journalReview article

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Abstract

Purpose: The combination of an oral fluoropyrimidine derivative, S-1, and irinotecan has been reported to be a promising regimen for advanced colorectal cancer. However, the safety and efficacy of bevacizumab (BV) to combine with irinotecan and S-1 has not been determined. The aim of the study was to determine the maximum tolerated dose (MTD) and recommended dose (RD) of BV combined with irinotecan plus S-1, and to observe the safety and efficacy of this regimen as second-line chemotherapy in patients with advanced colorectal cancer. Methods: This study initially had been planned as a phase I/II study. Eighty mg/m2 of irinotecan on days 1 and 8, 80 mg/m2 of S-1 for 14 consecutive days, and two doses of BV (Level 1; 10 mg/kg, Level -1; 7.5 mg/kg) were administered on day 1 every 3 weeks. Results: Fourteen patients were enrolled in phase I of the study between January 2008 and September 2010. Dose-limiting toxicities were diarrhea, abdominal pain, and infection. The MTD and RD of BV were determined to be 10 mg/kg and 7.5 mg/kg, respectively. The main adverse events were leukopenia, anorexia, and diarrhea. There were no treatment-related deaths. An independent review committee was scheduled to evaluate safety in phase I, but this trial closed early due to toxicity. Conclusions: This study identified the risk of gastrointestinal toxicity with the combination of irinotecan, S-1 and BV as second-line chemotherapy in patients with advanced colorectal cancer.

Original languageEnglish
Pages (from-to)29-34
Number of pages6
JournalCancer chemotherapy and pharmacology
Volume71
Issue number1
DOIs
Publication statusPublished - Jan 1 2013

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irinotecan
Chemotherapy
Colorectal Neoplasms
Drug Therapy
Toxicity
Maximum Tolerated Dose
Safety
Diarrhea
Leukopenia
Anorexia
Advisory Committees
Abdominal Pain
Bevacizumab
Derivatives

All Science Journal Classification (ASJC) codes

  • Oncology
  • Toxicology
  • Pharmacology
  • Cancer Research
  • Pharmacology (medical)

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Phase i study of bevacizumab combined with irinotecan and S-1 as second-line chemotherapy in patients with advanced colorectal cancer. / Kusaba, Hitoshi; Esaki, Taito; Kishimoto, Junji; Uchino, Keita; Arita, Shuji; Kumagai, Hozumi; Mitsugi, Kenji; Akashi, Koichi; Baba, Eishi.

In: Cancer chemotherapy and pharmacology, Vol. 71, No. 1, 01.01.2013, p. 29-34.

Research output: Contribution to journalReview article

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abstract = "Purpose: The combination of an oral fluoropyrimidine derivative, S-1, and irinotecan has been reported to be a promising regimen for advanced colorectal cancer. However, the safety and efficacy of bevacizumab (BV) to combine with irinotecan and S-1 has not been determined. The aim of the study was to determine the maximum tolerated dose (MTD) and recommended dose (RD) of BV combined with irinotecan plus S-1, and to observe the safety and efficacy of this regimen as second-line chemotherapy in patients with advanced colorectal cancer. Methods: This study initially had been planned as a phase I/II study. Eighty mg/m2 of irinotecan on days 1 and 8, 80 mg/m2 of S-1 for 14 consecutive days, and two doses of BV (Level 1; 10 mg/kg, Level -1; 7.5 mg/kg) were administered on day 1 every 3 weeks. Results: Fourteen patients were enrolled in phase I of the study between January 2008 and September 2010. Dose-limiting toxicities were diarrhea, abdominal pain, and infection. The MTD and RD of BV were determined to be 10 mg/kg and 7.5 mg/kg, respectively. The main adverse events were leukopenia, anorexia, and diarrhea. There were no treatment-related deaths. An independent review committee was scheduled to evaluate safety in phase I, but this trial closed early due to toxicity. Conclusions: This study identified the risk of gastrointestinal toxicity with the combination of irinotecan, S-1 and BV as second-line chemotherapy in patients with advanced colorectal cancer.",
author = "Hitoshi Kusaba and Taito Esaki and Junji Kishimoto and Keita Uchino and Shuji Arita and Hozumi Kumagai and Kenji Mitsugi and Koichi Akashi and Eishi Baba",
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T1 - Phase i study of bevacizumab combined with irinotecan and S-1 as second-line chemotherapy in patients with advanced colorectal cancer

AU - Kusaba, Hitoshi

AU - Esaki, Taito

AU - Kishimoto, Junji

AU - Uchino, Keita

AU - Arita, Shuji

AU - Kumagai, Hozumi

AU - Mitsugi, Kenji

AU - Akashi, Koichi

AU - Baba, Eishi

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Y1 - 2013/1/1

N2 - Purpose: The combination of an oral fluoropyrimidine derivative, S-1, and irinotecan has been reported to be a promising regimen for advanced colorectal cancer. However, the safety and efficacy of bevacizumab (BV) to combine with irinotecan and S-1 has not been determined. The aim of the study was to determine the maximum tolerated dose (MTD) and recommended dose (RD) of BV combined with irinotecan plus S-1, and to observe the safety and efficacy of this regimen as second-line chemotherapy in patients with advanced colorectal cancer. Methods: This study initially had been planned as a phase I/II study. Eighty mg/m2 of irinotecan on days 1 and 8, 80 mg/m2 of S-1 for 14 consecutive days, and two doses of BV (Level 1; 10 mg/kg, Level -1; 7.5 mg/kg) were administered on day 1 every 3 weeks. Results: Fourteen patients were enrolled in phase I of the study between January 2008 and September 2010. Dose-limiting toxicities were diarrhea, abdominal pain, and infection. The MTD and RD of BV were determined to be 10 mg/kg and 7.5 mg/kg, respectively. The main adverse events were leukopenia, anorexia, and diarrhea. There were no treatment-related deaths. An independent review committee was scheduled to evaluate safety in phase I, but this trial closed early due to toxicity. Conclusions: This study identified the risk of gastrointestinal toxicity with the combination of irinotecan, S-1 and BV as second-line chemotherapy in patients with advanced colorectal cancer.

AB - Purpose: The combination of an oral fluoropyrimidine derivative, S-1, and irinotecan has been reported to be a promising regimen for advanced colorectal cancer. However, the safety and efficacy of bevacizumab (BV) to combine with irinotecan and S-1 has not been determined. The aim of the study was to determine the maximum tolerated dose (MTD) and recommended dose (RD) of BV combined with irinotecan plus S-1, and to observe the safety and efficacy of this regimen as second-line chemotherapy in patients with advanced colorectal cancer. Methods: This study initially had been planned as a phase I/II study. Eighty mg/m2 of irinotecan on days 1 and 8, 80 mg/m2 of S-1 for 14 consecutive days, and two doses of BV (Level 1; 10 mg/kg, Level -1; 7.5 mg/kg) were administered on day 1 every 3 weeks. Results: Fourteen patients were enrolled in phase I of the study between January 2008 and September 2010. Dose-limiting toxicities were diarrhea, abdominal pain, and infection. The MTD and RD of BV were determined to be 10 mg/kg and 7.5 mg/kg, respectively. The main adverse events were leukopenia, anorexia, and diarrhea. There were no treatment-related deaths. An independent review committee was scheduled to evaluate safety in phase I, but this trial closed early due to toxicity. Conclusions: This study identified the risk of gastrointestinal toxicity with the combination of irinotecan, S-1 and BV as second-line chemotherapy in patients with advanced colorectal cancer.

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JO - Cancer Chemotherapy and Pharmacology

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