[Evaluation of efficacy and safety of adjuvant analgesics for peripheral neuropathy induced by cancer chemotherapy in digestive cancer patients-a pilot study].

After 1990's, the development of new generation anti-cancer agents produced encouraging improvement of prognosis in inoperable or relapsed stomach cancer and colorectal cancer. However, non-hematological toxicity, such as peripheral neuropathies, become a new dose-limiting toxicity. In several new generation drugs, measures for controlling peripheral neuropathy had not been established besides dose modification or schedule modification. We tried to control the peripheral neuropathy induced by anti-cancer agents with the assistance of an adjuvant analgesics ladder. A total of 18 digestive cancer patients who presented with peripheral neuropathy of grade 1 or more(NCI-CTCAE ver 3.0), in the chemotherapy including Taxol or Oxaliplatin, were enrolled. The first stage of the adjuvant analgesics ladder was set as the antidepressant(amoxapin), the second stage was anticonvulsive drugs(valproic acid or clonazepam) and the third stage was antiarrhythmic drug(mexiletine). In each stage, if the drug turned out to be ineffective after two / weeks follow-up, it shifted to the next stage. The response rate of each step was 61.1%(11/18)of the first stage, 50.0%(5/10)of the 2nd stage, 50.0%(2/4)of the 3rd stage, and the overall response rate was 77.8%. The discontinuance of cancer treatment by peripheral neuropathy was observed only in 1 patient 5.5%(1/18)in the Taxol administered group. The toxicity profile was skin eruption and drowsiness, but the skin eruption was observed only in 1 patient at the 3rd stage and the drowsiness in 2 patients at the 2nd stage. It appears that the method to control the peripheral neuropathy induced by anti-cancer agents with the assistance of adjuvant analgesics ladder was effective and safe, but a large-scale clinical trial was warranted.

Bin1 attenuation in breast cancer is correlated to nodal metastasis and reduced survival.

Clinical outcomes in breast cancer are likely influenced by modifier genes that affect tumor dormancy versus progression. The Bin1 gene encodes a nucleocytosolic adapter protein that suppresses neoplastic cell transformation and that is often attenuated in human breast carcinoma. Recent mouse genetic studies indicate that Bin1 loss cooperates with ras activation to drive progression of mammary carcinoma, establishing Bin1 as a negative modifier of tumor progression in breast cancer. In this study, we investigated whether immunohistochemical losses of nuclear Bin1 proteins in cases of human breast cancer were correlated to progression status. In American and Japanese groups of low or middle grade breast cancers, losses were associated with reduced survival and increased nodal metastasis, respectively. Taken together with recent findings from mouse genetic studies, these findings encourage further evaluation of the potential utility of Bin1 as a clinical prognostic marker in breast cancer.