DOSE-FINDING STUDY OF IRINOTECAN AND CISPLATIN PLUS CONCURRENT RADIOTHERAPY FOR UNRESECTABLE STAGE-III NON-SMALL-CELL LUNG-CANCER

Irinotecan hydrochloride (CPT-11) shows marked anti-tumour activity al one and in combination with cisplatin in non-small-cell lung cancer (N SCLC), It is necessary to investigate combined-modality therapy includ ing novel effective anti-cancer agents to improve long-term survival o f patients with unresectable stage III NSCLC, A phase I/II study of co ncurrent chemoradiotherapy with CPT-II 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 evaluat ed in 12 of them; one patient was ineligible. Chemotherapy was repeate d every 4 weeks for three courses. Radiation therapy was started on da y 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 course s of chemotherapy as a result of persistent leucopenia and neutropenic fever respectively. Three of six patients given level 2 therapy compl eted the scheduled treatment. Another three received only one and two courses of chemotherapy, two refused treatment because of diarrhoea an d one died of pneumonia. Radiation therapy was inadequate in these thr ee patients. As the CPT-11 dose intensity in this trial was low, becau se 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 ther apy completion rate, the trial was discontinued at level 2, Five patie nts at level 1 and three at level 2 showed partial responses, an overa ll response rate of 67%, Although neither MTD nor dose-limiting toxici ty could be identified, chemotherapy with CPT-11 and cisplatin plus co ncurrent radiation therapy was deemed unacceptable. We are now conduct ing a phase I/II study of chemotherapy using CPT-11 as a single agent in combination with radiation therapy.