Postoperative adjuvant cisplatin, doxorubicin, and cyclophosphamide (PAC) chemotherapy in women with high-risk endometrial carcinoma.

Because extrapelvic failure is common in women with high-risk endometrial carcinoma, the curative impact of adjuvant irradiation is limited. To address the issue of systemic failure, we prospectively treated 62 at-risk patients with postoperative chemotherapy between October 1985 and April 1992. Patients were considered eligible if they had grade 2 disease with mid- or outer one-third myometrial invasion, grade 3 tumor with any myometrial invasion, completely resected extrauterine disease, or variant histology (clear cell, papillary serous). Adjuvant therapy consisted of intravenous cisplatin (50 mg/m2), doxorubicin (50 mg/m2), and cyclophosphamide (500 mg/m2) given every 4 weeks for six courses. Toxicity was moderate: 31 patients (50%) had grade 3/4 neutropenia; dose reductions were mandated in 39 cases. However, there were only four hospital admissions for toxicity during 366 treatment cycles. All but three patients completed planned treatment. Recurrences have been noted in 14 of 29 patients with extrauterine disease and in 8 of 33 without. Eighteen of the 22 recurrences (82%) were outside the pelvis. At this writing, 17 patients with recurrence were dead, and 4 are alive with disease. Median time to recurrence was 13 months. Observed progression-free intervals for those with and without extrauterine disease are 26 and 36+ months, respectively, over a median follow-up period of 37 months. Actuarial 3-year survivals for those with and without extrauterine spread were 46 and 82%, respectively. Although adjuvant PAC did not prevent distant failure in women with extrauterine disease, the survival rate was greater than that anticipated for patients with disease confined to the uterus. A randomized trial comparing adjuvant irradiation to PAC is warranted in this subset.