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7-N-(对羟基苯基)-丝裂霉素C(KW-2083)对癌性胸膜炎的作用

[Effect of 7-N-(P-hydroxyphenyl)-mitomycin C (KW-2083) against pleuritis carcinomatosa].

作者信息

Shimizu E, Saijo N, Shinkai T, Eguchi K, Tominaga K, Nomori H, Sasaki Y, Garcia-Herreros P, Hoshi A

出版信息

Gan To Kagaku Ryoho. 1984 Jun;11(6):1290-5.

PMID:6732255
Abstract

Fourteen cases of adenocarcinoma with pleuritis carcinomatosa (lung cancer 10 cases, ovarian cancer 2 cases, colon cancer 2 cases) were treated with intra-pleural instillation of 7-N-(p-hydroxyphenyl)-mitomycin C (KW-2083), a derivative of mitomycin C. KW-2083 was administered at a dose of 40 mg once or twice weekly. In 14 evaluable patients, the rate of decrease of pleural fluid was 79%, and that of disappearance of tumor cells in pleural fluid was 64%. Median survival time (MST) from the beginning of treatment in all cases was 163 days. The toxicities of intrapleural instillation of KW-2083 were chest pain (86%), transient fever (64%), anorexia (64%), fatigability (29%), nausea (21%), vomiting (21%) and thrombocytopenia (nadir: 3.5 X 10(4)/mm3; 7%). Serum and pleural fluid KW-2083 concentrations have been measured in 3 patients after intrapleural administration of KW-2083. The mean half life of KW-2083 in serum and pleural fluid was 74 min (69-78 min) and 56 min (33-70 min), respectively. The peak serum KW-2083 concentration was 0.18 microgram/ml (0.06-0.24 microgram/ml).

摘要

14例伴有癌性胸膜炎的腺癌患者(肺癌10例、卵巢癌2例、结肠癌2例)接受了丝裂霉素C衍生物7-N-(对羟基苯基)-丝裂霉素C(KW-2083)胸膜腔内注射治疗。KW-2083的给药剂量为40mg,每周1次或2次。在14例可评估的患者中,胸水减少率为79%,胸水肿瘤细胞消失率为64%。所有病例从治疗开始的中位生存时间(MST)为163天。KW-2083胸膜腔内注射的毒性反应有胸痛(86%)、短暂发热(64%)、厌食(64%)、乏力(29%)、恶心(21%)、呕吐(21%)和血小板减少(最低点:3.5×10⁴/mm³;7%)。3例患者在胸膜腔内给予KW-2083后测定了血清和胸水KW-2083浓度。KW-2083在血清和胸水中的平均半衰期分别为74分钟(69 - 78分钟)和56分钟(33 - 70分钟)。血清KW-2083峰值浓度为0.18μg/ml(0.06 - 0.24μg/ml)。

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[Phase I study of KW2083 7-N-(p-hydroxyphenyl) mitomycin C].
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