TREATMENT OF LOCALLY ADVANCED CERVICAL-CANCER WITH CONCURRENT RADIATION AND INTRAARTERIAL CHEMOTHERAPY

The purpose of this study was to determine the maximum tolerated dose (MTD) and feasibility of treatment with sequential intraarterial FUDR and cisplatin administered with concurrent whole pelvis radiation (XRT ) to women with advanced cervical cancer. Sixteen patients with squamo us carcinoma of the cervix were prospectively treated in a Phase I stu dy. All tumors were stages IIb, IIIb, or IVa with diameters of greater than or equal to 7 cm. Patients underwent surgical staging with pelvi c and paraortic lymphadenectomy with placement of bilateral intra-arte rial catheters in the anterior division of the internal iliac arteries . The catheters terminated in separate subcutaneous ports. No patient had metastasis in the high common iliac or paraortic nodes, Patients r eceived a planned course of 40-50 Gy whole pelvis XRT followed by indi cated brachytherapy. During the first 2 weeks of whole pelvis XRT, pat ients received a l-hr infusion of FUDR and during the second 2 weeks a l-hr infusion of cisplatin, each delivered daily by external pump wit h the daily whole pelvis XRT fraction. Additional cisplatin was infuse d during brachytherapy, Five dose levels ranging from 6.5 to 27 mg/m(2 ) daily for FUDR and from 2 to 8 mg/m(2) daily for cisplatin were used . The MTD of FUDR and CDDP was dose level 4 (22.5 and 6.75 mg/m(2), re spectively). Dose-limiting toxicity was grade 3/4 nausea seen in three of four patients at dose level 5, No patient had neuro- or ototoxicit y, There was no grade 4 myelosuppression, Eight patients had a complet e response, and six had a partial response. Disease progressed in two, Mean follow-up was 22.4 months. At this writing, 10 patients had no e vidence of disease, 2 were alive with disease, and 4 had died of disea se. Median survival has not been reached. This is a well-tolerated reg imen with significant activity that warrants further investigation at dose level 4. (C) 1995 Academic Press, Inc.