Kodera Yasuhiro, Ito Seiji, Fujiwara Michitaka, Mochizuki Yoshinari, Ohashi Norifumi, Ito Yuichi, Nakayama Goro, Koike Masahiko, Yamamura Yoshitaka, Nakao Akimasa
Department of Surgery II, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
Int J Clin Oncol. 2006 Dec;11(6):449-53. doi: 10.1007/s10147-006-0618-x. Epub 2006 Dec 25.
Therapy guided by chemotherapy sensitivity and resistance assays may lead to rational treatment decisions. Paclitaxel, one of several new drugs for gastric carcinoma, has not been extensively evaluated by in vitro chemosensitivity tests.
Chemosensitivity testing by histoculture drug response assay (HDRA) was performed with fresh specimens of primary tumor from 113 patients with gastric carcinoma. The test was performed in medium containing paclitaxel at three different concentrations for the initial 45 samples. Correlations between the results of chemosensitivity testing, determined at the optimal concentration, and the patients' clinicopathologic factors and outcome were then assessed for all patients.
By analyzing the initial 45 samples, 10 microg/ml was considered the optimal concentration of paclitaxel for this test. HDRA was successfully performed for 100 of 113 samples and chemosensitivity, calculated as the percentage of optical density of a tumor treated with anticancer drugs in relation to the optical density of the tumor cultured in the medium only, was distributed widely at this concentration. No significant correlation was observed between chemosensitivity and age, sex, clinical stage, histopathologic type, and outcome of patients with gastric carcinoma.
A histoculture drug response assay can now be performed to predict the chemosensitivity of paclitaxel at the concentration found in the current study. The accuracy of the assay to actually predict survival needs to be validated by a prospective clinical trial involving patients who have received paclitaxel in the postoperative adjuvant setting.
化疗敏感性和耐药性检测指导下的治疗可能会带来合理的治疗决策。紫杉醇是治疗胃癌的几种新药之一,尚未通过体外化疗敏感性试验进行广泛评估。
对113例胃癌患者的原发性肿瘤新鲜标本进行组织培养药物反应分析(HDRA)化疗敏感性检测。对最初的45个样本,在含有三种不同浓度紫杉醇的培养基中进行检测。然后评估所有患者在最佳浓度下化疗敏感性检测结果与患者临床病理因素及预后之间的相关性。
通过分析最初的45个样本,10微克/毫升被认为是该检测中紫杉醇的最佳浓度。113个样本中有100个成功进行了HDRA检测,在该浓度下,化疗敏感性(以用抗癌药物处理的肿瘤光密度相对于仅在培养基中培养的肿瘤光密度的百分比计算)分布广泛。未观察到胃癌患者的化疗敏感性与年龄、性别、临床分期、组织病理学类型及预后之间存在显著相关性。
现在可以进行组织培养药物反应分析,以预测当前研究中发现浓度的紫杉醇的化疗敏感性。该检测实际预测生存的准确性需要通过一项涉及术后辅助治疗中接受紫杉醇治疗患者的前瞻性临床试验来验证。