Yokoyama A, Kurita Y, Saijo N, Tamura T, Noda K, Shimokata K, Matsuda T
Department of Internal Medicine, Niigata Cancer Center Hospital, Japan.
Br J Cancer. 1998 Jul;78(2):257-62. doi: 10.1038/bjc.1998.474.
Irinotecan hydrochloride (CPT-11) shows marked anti-tumour activity alone and in combination with cisplatin in non-small-cell lung cancer (NSCLC). It is necessary to investigate combined-modality therapy including novel effective anti-cancer agents to improve long-term survival of patients with unresectable stage III NSCLC. A phase I/II study of concurrent chemoradiotherapy with CPT-11 and cisplatin was conducted to determine the maximum tolerated dose (MTD) and efficacy in this group of patients. Thirteen previously untreated patients with unresectable stage IIIA/B NSCLC were enrolled and efficacy and toxicity was evaluated in 12 of them; one patient was ineligible. Chemotherapy was repeated every 4 weeks for three courses. Radiation therapy was started on day 2 of the first course of chemotherapy and 60 Gy in 30 fractions was given over 6 weeks. Four of six patients enrolled at level 1 completed the scheduled treatment. Another two received only one and two courses of chemotherapy as a result of persistent leucopenia and neutropenic fever respectively. Three of six patients given level 2 therapy completed the scheduled treatment. Another three received only one and two courses of chemotherapy, two refused treatment because of diarrhoea and one died of pneumonia. Radiation therapy was inadequate in these three patients. As the CPT-11 dose intensity in this trial was low, because of the necessity of omitting CPT-11 administration on days 8 and/or 15 as a result of leucopenia or diarrhoea, and the low radiation therapy completion rate, the trial was discontinued at level 2. Five patients at level 1 and three at level 2 showed partial responses, an overall response rate of 67%. Although neither MTD nor dose-limiting toxicity could be identified, chemotherapy with CPT-11 and cisplatin plus concurrent radiation therapy was deemed unacceptable. We are now conducting a phase I/II study of chemotherapy using CPT-11 as a single agent in combination with radiation therapy.
盐酸伊立替康（CPT-11）单独使用以及与顺铂联合使用时，在非小细胞肺癌（NSCLC）中均显示出显著的抗肿瘤活性。有必要研究包括新型有效抗癌药物在内的综合治疗方法，以提高不可切除的III期NSCLC患者的长期生存率。开展了一项关于CPT-11与顺铂同步放化疗的I/II期研究，以确定该组患者的最大耐受剂量（MTD）和疗效。纳入了13例先前未接受过治疗的不可切除的IIIA/B期NSCLC患者，其中12例评估了疗效和毒性；1例患者不符合条件。化疗每4周重复一次，共三个疗程。放疗在第一个化疗疗程的第2天开始，6周内分30次给予60 Gy。1级入组的6例患者中有4例完成了预定治疗。另外2例分别因持续性白细胞减少和中性粒细胞减少性发热仅接受了1个和2个疗程的化疗。接受2级治疗的6例患者中有3例完成了预定治疗。另外3例仅接受了1个和2个疗程的化疗，2例因腹泻拒绝治疗，1例死于肺炎。这3例患者的放疗不充分。由于该试验中CPT-11的剂量强度较低，因白细胞减少或腹泻而必须在第8天和/或第15天省略CPT-11给药，且放疗完成率较低，则该试验在2级时停止。1级的5例患者和2级的3例患者显示部分缓解，总缓解率为67%。虽然未确定MTD和剂量限制性毒性，但CPT-伊立替康和顺铂联合同步放疗被认为不可接受。我们目前正在开展一项I/II期研究，使用CPT-11作为单一药物联合放疗进行化疗。
