Treatment of early stage epithelial ovarian cancer with chemotherapy and abdomino-pelvic radiotherapy: Results of a prospective treatment protocol (original) (raw)

1998, International Journal of Radiation Oncology*Biology*Physics

Purpose/Objeetive: To test the hypothesis that combined modality treatment with chemotherapy and abdomino-pelvie radiotherapy (APRT) reduces abdomino-pelvic and distant recurrences and improves survival in patients with ovarian carcinoma. Materials and Methods: From 1991 to 1994, 93 patients with early stage, optimally debulked epithelial ovarian carcinoma were treated with combined chemotherapy and APRT following TAH-BSO and surgical staging. The patients ranged in age from 19 to 83 (median 57) years. There were 27 FIGO stage 1 tumors, 49 stage II tumors, and 17 stage III tumors. Patients with dense adherence of tumor in the pelvis and no evidence otherwise ofextra-ovatian disease were classified as having stage II tumors based on previous results from this center. The histologic type was endometrioid in 32, serous in 23, clear cell in 19, mucinous in 10, and other in 9. There were 14 grade 1 tumors, 47 grade 2 tumors, 31 grade 3 tumors, and grade was not recorded in 1 case. Ascites was present in 40 patients. Eight patients had residual pelvic tumor <2 cm in size after surgery. None of the patients had residual tumor in the abdomen. Treatment was assigned using a prognostic classification derived from a previous cohort of patients with ovarian cancer who were treated with APRT alone. Patients with stage 1, grade 1 tumors (2) received no adjuvant treatment. Patients with stage II, grade I tumors (9) were assigned to treatment with APRT alone. Patients with stage 1 or II, grade 2 or 3 completely resected tumors or stage 3, grade 1 tumors (66) were assigned to treatment with 2 cycles ofcisplatinum 50 mg/m 2 followed by APRT (DDP+APRT). Patients with stage II, grade 2 or 3 tumors with pelvic residuum or patients with stage 3, grade 2 or 3 tumors (16) were assigned to treatment with cyelophosphamide 500 mg/m 2 and eisplatinum 50 mg/m 2 followed by APRT (CP+APRT). APRT consisted o f22.5 Gy in 22 daily fractions to the abdomen, and 45 Gy in 29 daily fractions to the pelvis using 6°Co or 6 MV photons. The follow-up ranged from 0.8 to 6.1 (median 3.6) years. Results: There were 22 recurrences of ovarian cancer following treatment: 15 of these (68%) were in the abdomen or pelvis alone without involvement of distant sites. Nine patients died (8 of disease), 14 were alive with disease, and 70 were free of disease. The disease-free and overall actuarial survivals at 3 years for the entire cohort were 78% and 91% respectively. Only treatment group assignment significantly predicted disease-flee survival by univariate analysis (p=0.03). Patients assigned to receive RT alone had a 3 year DFS of 78%, DDP+APRT 84%, and CP+APRT 56%. There was no significant effect on outcome of age, stage (p"~0.07), grade, pelvic residuum, pelvic adherence (p=0.08), sta-face excrescences (p=0.06), rupture, or ascites. There was no significant difference in outcome between the present series and an historical group of patients treated with APRT alone (3 year DFS of 78% vs. 71% respectively, p=0.5). Thirteen patients (16%) had an unplanned interruption ofAPRT, 8 for neutropenia or thrombocytopenia and 3 for other reasons. The delay was limited to 1 or 2 days in 6 of these patients. APRT was abandoned entirely in 3 patients (4%). Erythrocyte transfusion was required in 7 patients (9%). Two patients (3%) developed bowel obstruction after DDP+APRT that resolved with conservative management. Conclusions: These results confirm that APRT is a safe, effective treatment for carefully selected, early stage, optimally debulked patients with epithelial ovarian cancer. The addition ofcisplafinum-based chemotherapy to APRT does not significantly improve outcome and may contribute to an increase in acute hematologic toxicity. Tumor most commonly recurs in the abdomen or pelvis following APRT, and this is not altered by the addition o fcisplatinum chemotherapy. Further study of APRT combined with newer cytotoxic drugs such as paclitaxel, or novel agents such as angiogenesis inhibitors, is warranted with the aim of enhancing abdomino-pelvic tumor control and survival.