CHEMOTHERAPY, EARLY SURGICAL REASSESSMENT, AND HYPERFRACTIONATED ABDOMINAL RADIOTHERAPY IN STAGE-III OVARIAN-CANCER - RESULTS OF A GYNECOLOGIC-ONCOLOGY-GROUP STUDY

Purpose: To determine outcomes and treatment toxicities in patients wi th optimal (less than or equal to 1 cm residual) Stage III ovarian car cinoma treated with three courses of cisplatin-cyclophosphamide, surgi cal reassessment (SRA), and hyperfractionated whole abdominal irradiat ion (WAI). Methods and Materials: Forty-two eligible patients entered this prospective Phase II study conducted by the Gynecologic Oncology Group (GOG). Disease characteristics were as follows: age range, 32-76 years (median 58); Stage IIIA (n = 1,2%), IIIB (n = 2,5%), IIIC (n = 39,93%); histology-serous papillary (n = 21,50%); other (n = 21,50%); Grade 1 (n = 1,2%); 2 (n = 14,33%); 3 (n = 27,54%); residual disease a fter initial surgery (present: n = 23,55%; absent: n = 19,45%). Five p atients progressed while on chemotherapy, could not be effectively cyt oreduced, and were not eligible for WAI. Of the remaining 37 patients, 35 received WAI. Surgical reassessment was not performed in five pati ents. Results: Of 37 patients with known SRA status after chemotherapy , 21 (57%) were grossly positive, 4 (11%) were microscopically positiv e, and 12 (32%) were negative. Based on measurements recorded followin g initial laparotomy and surgical reassessment, progression during che motherapy was noted in 40%, stage disease in 37%, and objective respon se in 23%. Toxicity during hyperfractionated WAI was limited and rever sible. No patient beginning WAI failed to complete or required a signi ficant treatment break. Following WAI, six patients underwent laparoto mies for abdominal symptoms; five had recurrent disease. Five addition al patients were managed conservatively for small bowel obstruction (S BO) or malabsorption, of whom three subsequently developed recurrence. Twenty-two patients having pelvic boosts were significantly more like ly to require management for gastrointestinal morbidity (p = 0.0021). Considering all eligible patients, median disease-free and overall sur vivals were 18.5 and 39 months, respectively. Considering patients com pleting chemotherapy and WAI, median disease-free and overall survival s were 24 and 46 months, respectively. Conclusions: (a) Disease progre ssion occurred within three cycles of cisplatin and cyclophosphamide c hemotherapy in 40% of patients with optimal (less than or equal to 1 c m residual) Sage III ovarian carcinoma. (b) Following limited chemothe rapy, hyper-fractionated WAI was acutely well tolerated. (c) Late radi ation-related toxicity was observed in only three patients (8.6%) in t he absence of recurrent disease. Late gastrointestinal morbidity was s ignificantly associated with the administration of a pelvic radiothera py (RT) boost. (d) Short duration chemotherapy followed by SRA and hyp erfractionated WAI without a pelvic boost is a promising management op tion for patients with optimal Stage III ovarian cancer. A Phase III t rial will be necessary to determine how this treatment strategy compar es with chemotherapy or RT alone in this patient population.