Hormonal Therapy The use of progestational agents for treatment of metastatic endometrial cancer was first described in 1961 when researchers observed an objective response rate of 29% in 21 patients (358). In a report from 1974, a beneficial response was observed in 35% of 308 patients (359). Subsequent reports noted somewhat less optimistic response rates, probably as a result of more strictly applied criteria for objective responses (359–362) (Table 35.12). Reports from Roswell Park Cancer Center and the Mayo Clinic observed objective response rates of 16% and 11%, respectively, with an additional 15% to 40% of patients exhibiting stable disease for at least 3 months (358,363). In 1986, the GOG reported on the use of oral medroxyprogesterone acetate for treatment of patients with advanced or recurrent endometrial cancer (361). Of 219 patients with measurable disease, 8% had a complete response, 6% had a partial response, 52% had stable disease, and 34% developed progressive disease within 1 month. The mean survival time for the entire group was 10.4 months. In a follow-up study comparing
Table 35.12 Response to Progestin Therapy in Advanced or Recurrent Endometrial Cancer
HPC, hydroxyprogesterone caproate (Delalutin); MPA, medroxyprogesterone acetate (Provera, Depo-Provera); MA, megestrol acetate (Megace); IM, intramuscular; PO, oral.
two different doses of oral medroxyprogesterone acetate, similar response rates were achieved (26% for 200 mg per day and 18% for 1,000 mg per day) (362). The type, dosage, and route of administration of the progestin seemed to have no effect on response in these studies.
The response of metastatic endometrial carcinoma to progestin therapy is related to several clinical and pathologic factors. Higher response rates are observed in well-differentiated tumors. A 20.5% response in low-grade tumors and only 1.4% response in high-grade tumors are noted (360). Likewise, the probability of an objective response to progestin therapy is about 70% for tumors that are estrogen-and progesterone-receptor positive, compared with about 5% to 15% for tumors that are negative for both receptors. A longer disease-free interval is associated with higher response rates to progestins. The response rate to progestinsranged from 6% in patients with an interval from primary treatment to recurrence of less than 6 months to 65% in patients in whom disease recurred more than 5 years after initial treatment (359). Other observed but less well-documented factors that may have an adverse effect on response to progestins are disease recurrence within a prior radiation field, large tumor burden, and advanced primary versus recurrent disease (360, 363).
A phase II investigation of the aromatase inhibitor anastrozole showed minimal activity in an unselected subset of patients with advanced or recurrent endometrial cancer (364).