High‐dose cisplatin in patients with advanced malignancies
High‐dose cisplatin in patients with advanced malignancies
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晚期恶性肿瘤患者的大剂量顺铂
作者：
M. Blumenreich;T. Woodcock;Mariesa K. Jones;S. Richman;P. Gentile;T. T. Kubota;J. Allegra
进行了一项研究，以确定顺铂（CDDP）是否可以在比平常更高的剂量下给予，利用积极的支持措施。12名患者进入CDDP的三个剂量水平：I级，180 mg/m2作为短输注给药; II级，220 mg/m2也作为短输注给药; III级，200 mg/m2分为五个每日剂量，每个剂量输注超过6小时。在所有情况下，将CDDP溶解并给予250 ml 5%盐水溶液。对于I级和II级，在治疗前24小时开始以200至250 ml/h D51/2NS静脉补液，并补充钾和镁，并在治疗后持续3至4天，如果恶心持续，则持续更长时间。在CDDP之前（25%溶液，50 ml推注）和之后（20%溶液，500 ml超过3小时）给予甘露醇。在III级，在治疗前一天开始使用相同的静脉（IV）液体进行水合，并在5天化疗完成后以200 - 250 ml/h的速度持续不间断至少24小时。每次每日剂量的CDDP之前注射甘露醇（25%溶液，50 ml推注），并伴随6小时输注1000 ml 20%甘露醇。3名患者接受了5个一级CDDP课程; 4名患者接受了7个二级课程; 5名患者接受了7个三级课程。耳毒性在3例患者中为剂量限制性II级。在I级两个疗程和II级两个疗程后，观察到血清肌酐一过性升高。所有病例的肾损害均无症状;不需要透析。在II级，两个疗程后观察到白细胞最低计数在1.0和2.0 × 103/mm 3之间，三个疗程后在2.0和3.0 × 103/mm 3之间。4个疗程后血小板最低值低于50 × 103/mm 3，1个疗程后血小板最低值在50 ~ 100 × 103/mm 3之间。恶心和呕吐经常发生，但可耐受。在III级，骨髓抑制具有剂量限制性。4个疗程后白细胞计数最低值为1.0 - 2.0 × 103/mm 3，1个疗程后白细胞计数最低值为2.0 - 3.0。3个疗程后血小板计数最低值低于50 × 103/mm 3; 2例患者需要预防性血小板输注。在进一步的三个疗程后，最低值在50和100 × 103血小板/mm 3之间。在三级时未发生耳毒性和肾毒性。在前列腺癌、非小细胞肺癌、食管腺癌和恶性纤维组织细胞瘤患者中，在所有三个剂量水平下均观察到缓解。得出的结论是，CDDP的剂量为200 mg/m2，分为5个每日部分，是可以耐受的，可以引入II期试验。
A study was conducted to determine if cisplatin (CDDP) can be given at higher doses than usual, utilizing aggressive supportive measures. Twelve patients were entered into three dose levels of CDDP: level I, 180 mg/m2 given as a short infusion; level II, 220 mg/m2 also given as a short infusion; level III, 200 mg/m2 divided in five daily doses, each infused over 6 hours. In all cases, CDDP was dissolved and given in 250 ml of a 5% saline solution. For levels I and II, intravenous hydration with 200 to 250 ml/hour D51/2NS with potassium and magnesium supplements, was started 24 hours before therapy and continued for 3 to 4 days after, longer if nausea persisted. Mannitol was given before (25% solution, 50 ml bolus) and after (20% solution, 500 ml over 3 hours) CDDP. At level III hydration with the same intravenous (IV) fluids was begun the day before therapy and continued without interruption at 200 to 250 ml/hour for a minimum of 24 hours after the completion of the 5 days of chemotherapy. Each daily dose of CDDP was preceded by injection of mannitol (25% solution, 50 ml bolus) and accompanied by a 6‐hour infusion of 1000 ml 20% mannitol. Three patients received five CDDP courses at level I; 4 patients, seven courses at level II; and 5 patients, seven courses at level III. Ototoxicity was dose‐limiting in three patients at level II. Transient elevation of serum creatinine was seen following two courses at level I and two courses at level II. The renal impairment was asymptomatic in all cases; dialysis was not needed. At level II, leukocyte nadir counts between 1.0 and 2.0 × 103/mm3 were seen following two courses and between 2.0 and 3.0 × 103/mm3 following three courses. Platelet nadir counts below 50 × 103/mm3 were recorded after four courses and between 50 and 100 × 103/mm3 after one course. Nausea and vomiting occurred frequently, but were tolerable. At level III, myelosuppression was dose‐limiting. Nadir leukocyte counts between 1.0 and 2.0 × 103/mm3 followed four courses and between 2.0 and 3.0 followed one course. Nadir platelet counts below 50 × 103/mm3 were seen after three courses; two patients required prophylactic platelet transfusions. Nadirs between 50 and 100 × 103 platelets/mm3 followed three further courses. Ototoxicity and nephrotoxicity did not occur at level III. Responses were seen in all three dose levels in patients with prostate carcinoma, non‐small cell lung cancer, adenocarcinoma of the esophagus, and malignant fibrous histiocytoma. It was concluded that CDDP at a dose of 200 mg/m2, divided in five daily fractions, is tolerable and can be introduced into Phase II trials.