Goshajinkigan oxaliplatin neurotoxicity evaluation (GONE): a phase 2, multicenter, randomized, double‑blind, placebo‑controlled trial of goshajinkigan to prevent oxaliplatin‑induced neuropathy.

Abstract

PURPOSE:

Oxaliplatin-induced peripheral neurotoxicity (OPN) is frequent and potentially severe, but successful treatment of this condition is still an unmet clinical need. We aimed to determine whether treatment with goshajinkigan (TJ-107), a traditional Japanese medicine, is better than placebo in preventing OPN in patients with advanced or recurrent colorectal cancer patients treated with standard FOLFOX regimens.

METHODS:

In this phase 2, randomized, double-blind, placebo-controlled study, patients undergoing oxaliplatin-based chemotherapy were randomized to receive either oral TJ-107 (7.5 g) or matching placebo daily. The severity of OPN was assessed according to the Common Toxicity Criteria for Adverse Events at baseline, every 2 weeks until the 8th cycle, and every 4 weeks thereafter until the 26th week. The primary endpoint was the incidence of grade 2 or greater OPN until the 8th cycle of chemotherapy.

RESULTS:

Analyses were done by intention to treat. Eighty-nine patients were randomly assigned to receive either TJ-107 (n = 44) or placebo (n = 45) between May 2009 and March 2010. The incidence of grade 2 or greater OPN until the 8th cycle was 39 and 51 % in the TJ-107 and placebo groups, respectively (relative risk (RR), 0.76; 95 % CI, 0.47–1.21). The incidence of grade 3 OPN was 7 % (TJ-107) vs. 13 % (placebo) (0.51, 0.14–1.92). No concerns regarding toxicity emerged with TJ-107 treatment.

CONCLUSIONS:

TJ-107 appears to have an acceptable safety margin and a promising effect in delaying the onset of grade 2 or greater OPN without impairing FOLFOX efficacy.

• Authors: Toru Kono, Taishi Hata, Satoshi Morita, Yoshinori Munemoto, Takanori Matsui, Hiroshi Kojima, Hiroyoshi Takemoto, Mutsumi Fukunaga, Naoki Nagata, Mitsuo Shimada, Junichi Sakamoto, Hideyuki Mishima
• Journal: Cancer chemotherapy and pharmacology (Cancer Chemother Pharmacol) Vol. 72 Issue 6 Pg. 1283-90 (Dec 2013) ISSN: 1432-0843 [Electronic] Germany
• PMID: 24121454 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Drugs, Chinese Herbal
• Organoplatinum Compounds
• gosha-jinki-gan
• Oxaliplatin
• Leucovorin
• Fluorouracil

Topics

• Administration, Oral
• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Colorectal Neoplasms (drug therapy)
• Double-Blind Method
• Drugs, Chinese Herbal (adverse effects, therapeutic use)
• Female
• Fluorouracil (adverse effects, therapeutic use)
• Humans
• Incidence
• Leucovorin (adverse effects, therapeutic use)
• Male
• Middle Aged
• Neoplasm Recurrence, Local
• Neurotoxicity Syndromes (etiology, prevention & control)
• Organoplatinum Compounds (administration & dosage, adverse effects, therapeutic use)
• Oxaliplatin
• Peripheral Nervous System Diseases (chemically induced, prevention & control)
• Severity of Illness Index
• Time Factors
• Treatment Outcome