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顺铂、阿霉素和卡波醌新联合化疗方案治疗晚期前列腺癌的实验研究与临床应用

[Experimental study and clinical application of a new combination chemotherapy with cis-platinum, adriamycin and carboquone in patients with advanced prostate cancer].

作者信息

Ito H

机构信息

Department of Urology, Nippon Medical School, Tokyo, Japan.

出版信息

Nihon Ika Daigaku Zasshi. 1995 Oct;62(5):456-68. doi: 10.1272/jnms1923.62.456.

Abstract

In vitro chemosensitivity of established cell lines from human prostate cancer (8 PC 93, 19 PC 93, DU 145 and PC 3) to various anticancer drugs was examined by clonogenic assay. The drugs used were aclarubicin (ACR), adriamycin (ADM), carboquone (CQ), vincristine (VCR), ifosfamide (IFM), peplomycin (PEP) and cis-platinum (CDDP). To compare antitumor activity of different drugs, the predicted anticancer activity (PAA) was calculated from the 50% inhibition doses and the peak plasma concentration of the clinically used dose. High antitumor activity of drug was considered if PAA > or = 1 was observed. The chemosensitivities were: CQ > ADM > CDDP > VCR > PEP > IFM > ACR in the clonogenic assay. 19 PC 93 and DU 145 were sensitive to CQ, ADM and CDDP, but 8 PC 93 and PC 3 were sensitive to CQ, ADM, CDDP and VCR. Thus, a new combination chemotherapy with CDDP, ADM and CQ (PAQ therapy) was used clinically. PAQ therapy was given to sixteen patients with stage D advanced prostate cancer. Of these patients, 14 were undergoing relapse from antiandrogen therapy and 2 had hormone-resistant prostate cancer. The mean interval from the start of the prior treatment to relapse of the cancer was 18 months. The effectiveness of the new therapy was judged according to the response criteria for prostate cancer treatment of Japan. Three patients showed partial response (PR), 9 were stable disease (Stable) and 4 showed progressive disease (PD). The mean response duration in the patients with PR and with Stable was 11.6 months. The survival length of the responders (PR + Stable) was significantly longer than that of the nonresponders (PD) (p < 0.001). The side effect of PAQ therapy was lower than the moderate degree. Therefore, we considered PAQ therapy to be one of the clinical trials for the treatment of advanced prostate cancer.

摘要

通过克隆形成试验检测了来自人前列腺癌的已建立细胞系(8 PC 93、19 PC 93、DU 145和PC 3)对各种抗癌药物的体外化学敏感性。所使用的药物有阿柔比星(ACR)、阿霉素(ADM)、卡波醌(CQ)、长春新碱(VCR)、异环磷酰胺(IFM)、培洛霉素(PEP)和顺铂(CDDP)。为比较不同药物的抗肿瘤活性,根据50%抑制剂量和临床使用剂量的血浆峰值浓度计算预测抗癌活性(PAA)。如果观察到PAA≥1,则认为药物具有高抗肿瘤活性。克隆形成试验中的化学敏感性顺序为:CQ>ADM>CDDP>VCR>PEP>IFM>ACR。19 PC 93和DU 145对CQ、ADM和CDDP敏感,但8 PC 93和PC 3对CQ、ADM、CDDP和VCR敏感。因此,临床上使用了一种新的以CDDP、ADM和CQ组成的联合化疗(PAQ疗法)。对16例D期晚期前列腺癌患者给予PAQ疗法。这些患者中,14例正在接受抗雄激素治疗后复发,2例患有激素抵抗性前列腺癌。从开始先前治疗到癌症复发的平均间隔时间为18个月。根据日本前列腺癌治疗的反应标准判断新疗法的有效性。3例患者出现部分缓解(PR),9例病情稳定(Stable),4例病情进展(PD)。PR和Stable患者的平均缓解持续时间为11.6个月。有反应者(PR + Stable)的生存长度明显长于无反应者(PD)(p<0.001)。PAQ疗法的副作用低于中度。因此,我们认为PAQ疗法是晚期前列腺癌治疗的临床试验之一。

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