Abstract P1-15-11: The Kampo medicine Goshajinkigan prevents docetaxel-related peripheral neuropathy in breast cancer patients

Abstract

Background: Although taxanes have become a key chemotherapeutic drug in breast cancer treatment. Taxanes inhibit the growth of cancer cells by disrupting the functioning of their microtubules; however, the microtubules of nerve cells are also affected by this process, which can cause neurological disorders. The Kampo medicine Goshajinkigan (GJG) is a traditional Japanese medicine that is used for the treatment of several neurological symptoms including pain and numbness, GJG is comprised of 10 herbs, each of which contains numerous active ingredients. Recently, GJG has been reported to prevent anticancer drug-induced peripheral neuropathy in colorectal cancer. We performed the present prospective randomized study to confirm the effects of GJG and mecobalamin (B12) against docetaxel (DOC)-associated peripheral neurotoxicity in breast cancer patients. Patients and method: Between May 2007 and April 2011, 60 breast cancer patients were treated with DOC. Thirty-three patients (GJG group) received oral administration of 7.5 g/day GJG and 27 patients (B12 group) received oral administration of 1500 μg/day B12. The patients were treated with TC (75mg/m2 docetaxel and 600 mg/m2 cyclophosphamide) every 3 weeks for 4 cycles, docetaxel alone (100mg/m2) every 3 weeks for 4 cycles, and XT (900mg/m2 capecitabine administered orally twice a day on days 1–14 plus 60 mg/m2 docetaxel) every 3 weeks for 6 cycles. Peripheral neuropathy was evaluated during every course according to DEB-NTC (Neurotoxicity Criteria of Debiopharm), Common Terminology Criteria for Adverse Events (NCI-CTC) ver.3.0, and a visual analogue scale (VAS). Results: The median age of the GJG group was 58 years old (35 to 70 years old), the B12 group was 55 years old (33 to 69 years old), and they were all females. For the regimens, in the GJG group, TC, DOC only, and XT were administered in 19 cases, 13 cases and 1 case, respectively. In the B12 group, they were 15 cases, 11 cases and 12 cases, respectively. The cumulative dose of DOC was 338.5 mg/m2 in the GJG group, and 340 mg/m2 in the B12 group. Peripheral neuropathy occurred significantly less frequently in the GJG group (39.3%) than the B12 group (88.9%) (p < 0.01). In the GJG group, grade 1 DEB-NTC was observed in 2 cases, grade 2 in 5 cases and grade 3 in 5 cases. Grade 1 NCI-CTC was observed in 7 cases, grade 2 in 6 cases. In the B12 group, grades 1, 2 and 3 DEB-NTC were observed in one case, 12 cases and 12 cases, respectively; and grades 1, 2 and 3 NCI-CTC were observed in 11 cases, 12 cases and one case. The mean VAS scores for numbness after chemotherapy were 2.7 in the GJG group and 4.9 in the B12 group (p < 0.01). The incidence of grade 2/3 peripheral neuropathy was lower in the GJG group than the B12 group. Peripheral neuropathy was significantly controlled in the GJG group. Conclusion: The present study is the first prospective control study to prove the efficacy of GJG against docetaxel-induced peripheral neuropathy in breast cancer patients. Our findings suggest that DOC-associated peripheral neurotoxicity can be suppressed by the administration of GJG. It will be necessary to confirm the usefulness of GJG in larger prospective studies. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-15-11.