Preventive effect of Goshajinkigan on peripheral neurotoxicity of FOLFOX therapy (GENIUS trial): a placebo-controlled, double-blind, randomized phase III study

Eiji Oki, Yasunori Emi, Hiroshi Kojima, Jun Higashijima, Takeshi Kato, Yasuhiro Miyake, Masanori Kon, Yutaka Ogata, Kenichi Takahashi, Hideyuki Ishida, Hiroshi Saeki, Yoshihisa Sakaguchi, Takeharu Yamanaka, Toru Kono, Naohiro Tomita, Hideo Baba, Ken Shirabe, Yoshihiro Kakeji, Yoshihiko Maehara

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Abstract

Background: Peripheral sensory neurotoxicity is a frequent adverse effect of oxaliplatin therapy. Calcium and magnesium (Ca/Mg) infusions are frequently used as preventatives, but a recent phase III trial failed to show that they prevent neurotoxicity. We therefore conducted a multicenter randomized phase III trial to compare fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) with and without Goshajinkigan (GJG), a traditional Japanese herbal medicine (Kampo), to determine GJG’s potential for reducing peripheral neuropathy in patients with colorectal cancer. Methods: Patients with colon cancer who were undergoing adjuvant therapy with infusional mFOLFOX6 were randomly assigned to GJG (7.5 mg three times daily) or placebo in a double-blind manner. The primary endpoint was the time to grade 2 or greater neuropathy, which was determined at any point during or after oxaliplatin-based therapy using version 3 of the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE). Findings: An interim analysis was performed when 142 of the planned 310 patients had been enrolled and the safety assessment committee recommended that the study be discontinued. One hundred eighty-two patients were evaluable for response. They included 89 patients in the GJG group and 93 patients in the placebo group. The incidence of grade 2 or greater neurotoxicity was 50.6 % in the GJG group and 31.2 % in the placebo group. A Cox proportional hazards analysis indicated that the use of GJG was significantly associated with the incidence of neuropathy (hazard ratio, 1.908; p = 0.007). Conclusion: Goshajinkigan did not prevent oxaliplatin-associated peripheral neuropathy in this clinical trial. The clinical study was therefore terminated.

Original languageEnglish
Pages (from-to)767-775
Number of pages9
JournalInternational Journal of Clinical Oncology
Volume20
Issue number4
DOIs
Publication statusPublished - Aug 8 2015

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oxaliplatin
Placebos
Peripheral Nervous System Diseases
Therapeutics
Kampo Medicine
Leucovorin
National Cancer Institute (U.S.)
Herbal Medicine
Incidence
Terminology
Fluorouracil
Colonic Neoplasms
Magnesium
gosha-jinki-gan
Colorectal Neoplasms
Clinical Trials
Calcium
Safety

All Science Journal Classification (ASJC) codes

  • Surgery
  • Hematology
  • Oncology

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Preventive effect of Goshajinkigan on peripheral neurotoxicity of FOLFOX therapy (GENIUS trial) : a placebo-controlled, double-blind, randomized phase III study. / Oki, Eiji; Emi, Yasunori; Kojima, Hiroshi; Higashijima, Jun; Kato, Takeshi; Miyake, Yasuhiro; Kon, Masanori; Ogata, Yutaka; Takahashi, Kenichi; Ishida, Hideyuki; Saeki, Hiroshi; Sakaguchi, Yoshihisa; Yamanaka, Takeharu; Kono, Toru; Tomita, Naohiro; Baba, Hideo; Shirabe, Ken; Kakeji, Yoshihiro; Maehara, Yoshihiko.

In: International Journal of Clinical Oncology, Vol. 20, No. 4, 08.08.2015, p. 767-775.

Research output: Contribution to journalArticle

Oki, E, Emi, Y, Kojima, H, Higashijima, J, Kato, T, Miyake, Y, Kon, M, Ogata, Y, Takahashi, K, Ishida, H, Saeki, H, Sakaguchi, Y, Yamanaka, T, Kono, T, Tomita, N, Baba, H, Shirabe, K, Kakeji, Y & Maehara, Y 2015, 'Preventive effect of Goshajinkigan on peripheral neurotoxicity of FOLFOX therapy (GENIUS trial): a placebo-controlled, double-blind, randomized phase III study', International Journal of Clinical Oncology, vol. 20, no. 4, pp. 767-775. https://doi.org/10.1007/s10147-015-0784-9
Oki, Eiji ; Emi, Yasunori ; Kojima, Hiroshi ; Higashijima, Jun ; Kato, Takeshi ; Miyake, Yasuhiro ; Kon, Masanori ; Ogata, Yutaka ; Takahashi, Kenichi ; Ishida, Hideyuki ; Saeki, Hiroshi ; Sakaguchi, Yoshihisa ; Yamanaka, Takeharu ; Kono, Toru ; Tomita, Naohiro ; Baba, Hideo ; Shirabe, Ken ; Kakeji, Yoshihiro ; Maehara, Yoshihiko. / Preventive effect of Goshajinkigan on peripheral neurotoxicity of FOLFOX therapy (GENIUS trial) : a placebo-controlled, double-blind, randomized phase III study. In: International Journal of Clinical Oncology. 2015 ; Vol. 20, No. 4. pp. 767-775.
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abstract = "Background: Peripheral sensory neurotoxicity is a frequent adverse effect of oxaliplatin therapy. Calcium and magnesium (Ca/Mg) infusions are frequently used as preventatives, but a recent phase III trial failed to show that they prevent neurotoxicity. We therefore conducted a multicenter randomized phase III trial to compare fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) with and without Goshajinkigan (GJG), a traditional Japanese herbal medicine (Kampo), to determine GJG’s potential for reducing peripheral neuropathy in patients with colorectal cancer. Methods: Patients with colon cancer who were undergoing adjuvant therapy with infusional mFOLFOX6 were randomly assigned to GJG (7.5 mg three times daily) or placebo in a double-blind manner. The primary endpoint was the time to grade 2 or greater neuropathy, which was determined at any point during or after oxaliplatin-based therapy using version 3 of the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE). Findings: An interim analysis was performed when 142 of the planned 310 patients had been enrolled and the safety assessment committee recommended that the study be discontinued. One hundred eighty-two patients were evaluable for response. They included 89 patients in the GJG group and 93 patients in the placebo group. The incidence of grade 2 or greater neurotoxicity was 50.6 {\%} in the GJG group and 31.2 {\%} in the placebo group. A Cox proportional hazards analysis indicated that the use of GJG was significantly associated with the incidence of neuropathy (hazard ratio, 1.908; p = 0.007). Conclusion: Goshajinkigan did not prevent oxaliplatin-associated peripheral neuropathy in this clinical trial. The clinical study was therefore terminated.",
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T1 - Preventive effect of Goshajinkigan on peripheral neurotoxicity of FOLFOX therapy (GENIUS trial)

T2 - a placebo-controlled, double-blind, randomized phase III study

AU - Oki, Eiji

AU - Emi, Yasunori

AU - Kojima, Hiroshi

AU - Higashijima, Jun

AU - Kato, Takeshi

AU - Miyake, Yasuhiro

AU - Kon, Masanori

AU - Ogata, Yutaka

AU - Takahashi, Kenichi

AU - Ishida, Hideyuki

AU - Saeki, Hiroshi

AU - Sakaguchi, Yoshihisa

AU - Yamanaka, Takeharu

AU - Kono, Toru

AU - Tomita, Naohiro

AU - Baba, Hideo

AU - Shirabe, Ken

AU - Kakeji, Yoshihiro

AU - Maehara, Yoshihiko

PY - 2015/8/8

Y1 - 2015/8/8

N2 - Background: Peripheral sensory neurotoxicity is a frequent adverse effect of oxaliplatin therapy. Calcium and magnesium (Ca/Mg) infusions are frequently used as preventatives, but a recent phase III trial failed to show that they prevent neurotoxicity. We therefore conducted a multicenter randomized phase III trial to compare fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) with and without Goshajinkigan (GJG), a traditional Japanese herbal medicine (Kampo), to determine GJG’s potential for reducing peripheral neuropathy in patients with colorectal cancer. Methods: Patients with colon cancer who were undergoing adjuvant therapy with infusional mFOLFOX6 were randomly assigned to GJG (7.5 mg three times daily) or placebo in a double-blind manner. The primary endpoint was the time to grade 2 or greater neuropathy, which was determined at any point during or after oxaliplatin-based therapy using version 3 of the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE). Findings: An interim analysis was performed when 142 of the planned 310 patients had been enrolled and the safety assessment committee recommended that the study be discontinued. One hundred eighty-two patients were evaluable for response. They included 89 patients in the GJG group and 93 patients in the placebo group. The incidence of grade 2 or greater neurotoxicity was 50.6 % in the GJG group and 31.2 % in the placebo group. A Cox proportional hazards analysis indicated that the use of GJG was significantly associated with the incidence of neuropathy (hazard ratio, 1.908; p = 0.007). Conclusion: Goshajinkigan did not prevent oxaliplatin-associated peripheral neuropathy in this clinical trial. The clinical study was therefore terminated.

AB - Background: Peripheral sensory neurotoxicity is a frequent adverse effect of oxaliplatin therapy. Calcium and magnesium (Ca/Mg) infusions are frequently used as preventatives, but a recent phase III trial failed to show that they prevent neurotoxicity. We therefore conducted a multicenter randomized phase III trial to compare fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) with and without Goshajinkigan (GJG), a traditional Japanese herbal medicine (Kampo), to determine GJG’s potential for reducing peripheral neuropathy in patients with colorectal cancer. Methods: Patients with colon cancer who were undergoing adjuvant therapy with infusional mFOLFOX6 were randomly assigned to GJG (7.5 mg three times daily) or placebo in a double-blind manner. The primary endpoint was the time to grade 2 or greater neuropathy, which was determined at any point during or after oxaliplatin-based therapy using version 3 of the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE). Findings: An interim analysis was performed when 142 of the planned 310 patients had been enrolled and the safety assessment committee recommended that the study be discontinued. One hundred eighty-two patients were evaluable for response. They included 89 patients in the GJG group and 93 patients in the placebo group. The incidence of grade 2 or greater neurotoxicity was 50.6 % in the GJG group and 31.2 % in the placebo group. A Cox proportional hazards analysis indicated that the use of GJG was significantly associated with the incidence of neuropathy (hazard ratio, 1.908; p = 0.007). Conclusion: Goshajinkigan did not prevent oxaliplatin-associated peripheral neuropathy in this clinical trial. The clinical study was therefore terminated.

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