TWICE-DAILY FRACTIONATION OF EXTERNAL IRRADIATION WITH BRACHYTHERAPY AND CHEMOTHERAPY IN CARCINOMA OF THE CERVIX WITH POSITIVE PARAAORTIC LYMPH-NODES - PHASE-II STUDY OF THE RADIATION-THERAPY ONCOLOGY GROUP-92-10

Purpose: The purpose of this study was to evaluate the toxicity and ef ficacy of twice-daily external irradiation to the pelvis and para-aort ics with brachytherapy and concurrent chemotherapy for carcinoma of th e cervix with positive para-aortic lymph nodes. Methods and Materials: This study was designed to administer twice-daily radiation doses of 1.2 Gy to the pelvis and para-aortics at 4- to 6-h intervals, 5 days p er week. The total external radiation doses were 24 to 48 Gy to the wh ole pelvis, 12 to 36 Gy parametrial boost, and 48 Gy to the para-aorti cs with an additional boost to a total dose of 54 to 58 Gy to the know n metastatic para-aortic site. One or two intracavitary applications w ere performed to deliver a total minimum dose of 85 Gy to point A. Cis platin (75 mg/m(2), days 1 and 22) and 5-FU (1000 mg/m(2)/24 h x 4 day s; days 1 and 22) were given for two or three cycles. Results: Twenty- nine patients with clinical Stages I to TV carcinoma of the cervix wit h biopsy-proven para-aortic lymph nodes were enrolled in this study. H yperfractionated external radiotherapy was completed in 86% (25 of 29) . Brachytherapy was given in two applications to 48% (14 of 29), 31% ( 9 of 29) had one intracavitary application, 14% (4 of 29) had no brach ytherapy, one had three applications, and one had five HDR application s. Radiotherapy was completed per protocol in 69%. Three courses of ch emotherapy were given to 24% (7 of 29), 72% (21 of 29) received two co urses, and one patient did not receive chemotherapy. The acute toxicit y from chemotherapy was Grade 1 in 3%, Grade 2 in 17%, Grade 3 in 48%, and Grade 4 in 28%. Radiotherapy toxicity was Grade 1 in 7%, Grade 2 in 34%, Grade 3 in 21%, and Grade 4 in 28%. One Grade 5 toxicity occur red and the patient died from a myocardial infarction from chemotherap y and radiotherapy colitis during her course of therapy. The median fo llow-up time was 18.9 months. The overall survival estimates were 59% at 1 year and 47% at 2 years. The probability of local-regional failur e was 38% at 1 year and 49% at 2 years. The probability of disease fai lure at any site was 45% at 1 gear and 59% at 2 years. Conclusion: The results suggest that twice-daily external irradiation to the pelvis a nd para-aortics with brachy-therapy and concurrent chemotherapy result ed in an unacceptably high rate (31%, 9 of 29) of Grade 4 nonhematolog ic toxicity. One patient died from complications of therapy. Radiother apy was completed per protocol in 69%. The survival estimates appear n o better than standard fractionation radiotherapy without chemotherapy . Additional follow-up is necessary for long-term survival estimates. (C) 1998 Elsevier Science Inc.