Von Hoff D D, Coltman C A, Forseth B
Cancer Res. 1981 May;41(5):1853-5.
We have utilized a recently developed human tumor cloning system to screen for antitumor effects in vitro of a new anthracenedione derivative, Mitoxantrone. The object was to determine if the system is useful for pinpointing the types of tumors in patients which should be studied in early Phase II clinical trials. Tumors from 267 patients were placed in culture (20 different histological tumor types). One hundred seventy tumors both grew and formed enough colonies for drug sensitivity assays. Excellent in vitro antitumor activity was noted for Mitoxantrone against human adenocarcinoma of the lung, small cell lung cancer, melanoma, and biliary tree cancer. Good antitumor activity was noted against breast cancer, ovarian cancer, non-Hodgkin's lymphoma, head and neck cancer, squamous cell lung cancer, soft tissue sarcoma, gastric cancer, and hepatomas. The drug showed no in vitro activity against colon cancer. These data indicate that Mitoxantrone has a wide spectrum of in vitro antitumor activity. A comparison of these in vitro results with the results of Phase II clinical trials with the drug should allow an evaluation of the utility of the human tumor cloning system for predicting clinical antitumor activity of a new compound.
我们利用一种最近开发的人类肿瘤克隆系统,来筛选一种新的蒽二酮衍生物米托蒽醌的体外抗肿瘤作用。目的是确定该系统是否有助于找出那些在II期临床试验早期应予以研究的患者肿瘤类型。来自267名患者的肿瘤被置于培养中(20种不同组织学类型的肿瘤)。170个肿瘤生长并形成了足够的集落用于药物敏感性测定。米托蒽醌对人肺腺癌、小细胞肺癌、黑色素瘤和胆管癌显示出优异的体外抗肿瘤活性。对乳腺癌、卵巢癌、非霍奇金淋巴瘤、头颈癌、肺鳞状细胞癌、软组织肉瘤、胃癌和肝癌显示出良好的抗肿瘤活性。该药物对结肠癌未显示出体外活性。这些数据表明米托蒽醌具有广泛的体外抗肿瘤活性。将这些体外结果与该药物的II期临床试验结果进行比较,应能评估人类肿瘤克隆系统在预测新化合物临床抗肿瘤活性方面的效用。