ORLANDONearly three decades of clinical trials of multiagent chemotherapy have yet to exceed the results produced in a study from the 1970s of sequential surgery, abdominopelvic radiotherapy and single-agent alkylating chemotherapy, said Ellen E. Bellairs, MD, of the University of Minnesota.
The 5-year results of the study were published in 1989 in Cancer (Potish et al). Dr. Bellairs revisited the Minnesota trial data and reported the 25-year outcomes at the American Society of Therapeutic Radiology and Oncology meeting.
Of 94 evaluable women with stage I-III epithelial ovarian cancer treated from 1970 to 1976, 19 had stage I disease; 25, stage II; and 50, stage III. Of the stage III patients, 21 had no palpable disease and 29 had palpable disease postoperatively.
Only 75% of the patients had hysterectomies, so the rest had a less optimal operation with either a bilateral or unilateral oophorectomy, Dr. Bellairs said.
She noted that 25 years ago, selection factors were not as stringent as they are today. The study essentially included everyone who was referred to Radiation Oncology; we even had an 82-year-old woman, she said. The study also included seven women with a concurrent or previous cancer diagnosis, patients who more than likely would have been excluded from a similar trial done today.
All patients received 20 Gy to the whole abdomen with fraction size of 1 Gy/d and a 29.75 Gy pelvic boost of 1.75 Gy/d. Patients then received 10 courses of melphalan, 1 mg/kg. All recurrences, except for two, were noted within the first 27 months; after 8 years, there were no recurrences or treatment-related deaths.
Overall and Disease-Free Survival
Overall 5-year survival was 42%, and at 10, 15, and 20 years, it was 30%, 23%, and 22%, respectively, Dr. Bellairs said. The overall survival curve was compared with the survival curve of a similarly aged cohort of healthy women alive in 1970. After 8 years, the curves became parallel.
Disease-free survival was 54% at 5 years and remained at 50% from 10 to 25 years. Disease-free survival at 25 years was 95% for those with stage I disease; for stage II patients, it was 71% at 5 years and 66% at 10 to 25 years.
Among stage III patients, most of those with palpable disease postoperatively were dead within 2 years; those who did not have palpable disease after surgery showed a 17% disease-free survival rate at 5 years and 11% thereafter.
Acute toxicity was tolerable. Chronic toxicity included small bowel obstruction requiring surgery (11.7%) and fatal hematologic toxicity (3%), including two cases of acute myelogenous leukemia and one case of thrombocytopenia.
Dr. Bellairs said that while radiation therapy has fallen out of vogue in favor of multiagent chemotherapy, this study shows that radiation therapy deserves a second look, especially considering the advances in technology and treatment since the 1970s. These include debulking surgery, advanced imaging technologies, tumor markers such as OC125, and use of better chemotherapeutic agents such as paclitaxel (Taxol), as well as advances in radiation therapy technology itself.
In the 1970s, patients received radiation therapy to only one field each day, whereas today, multiple fields are treated on a daily basis, Dr. Bellairs said. She also noted that 25 years ago, less optimal antiemetic regimens were used, and several advances in supportive care are now widely available. Further prospective randomized studies of the relationship of radiotherapy and chemotherapy in the postoperative management of ovarian cancer are needed, she concluded.