TWICE-DAILY FRACTIONATION OF EXTERNAL IRRADIATION WITH BRACHYTHERAPY IN BULKY CARCINOMA OF THE CERVIX - PHASE I II STUDY OF THE RADIATION-THERAPY ONCOLOGY GROUP-88-05/

Background. Hyperfractionated radiation therapy (HFX), which may permi t higher total doses of radiation therapy without increased toxic effe cts to normal tissues, has been used with pelvic tumors, but its combi nation with brachytherapy has not been well studied. Methods. A prospe ctive Phase I/II trial was designed to study HFX with brachytherapy in patients with bulky Stage IB and IIA, IIB, III, and IVA carcinomas of the cervix. HFX doses of 1.2 Gy were administered to the whole pelvis twice daily at 4-6 hour intervals, 5 days per week; the total dose to the whole pelvis was 24-48 Gy. External pelvic irradiation was follow ed by one or two intracavitary applications to deliver the total minim um dose of 85 Gy at point A and 65 Gy to the lateral pelvic nodes. Res ults. Eighty-one patients were enrolled in this protocol; 14% had Stag e IB, 43% stage II, 38% stage III, and 4% stage IVA carcinomas. Sevent y-one patients were evaluable for HFX and brachytherapy; 38 patients r eceived one intracavitary application, and 33 received two application s. Four patients had Grade 3 acute reactions. The cumulative rates of Grade 3-4 late toxicities were 1.9% at 1 year, and 6.3% at 2 and 3 yea rs. Of 80 patients evaluated for response, 80% had complete disappeara nce of disease. Comparisons with historical rates of late toxicity wit h standard fractionation (STD) revealed similar results in spite of hi gher total doses with HEX. Comparisons between historical STD and HPX also revealed equivalent rates of pelvic tumor control, Grade 3-4 toxi city, and survival at 3 years. Conclusions. Results suggest that combi ned with brachytherapy, HFX at total parametrial doses 10% above those used with STD was tolerated and at least as effective as STD. Further study with higher doses and extended fields is indicated. Comparisons of long term (5-plus years) survival and late-effects rates with STD versus HFX are planned.