There is currently no standard therapy for patients with recurrent disease. These patients should be entered into an ongoing clinical trial.
Patients who present with uterine sarcoma have been treated on a series of phase II studies by the Gynecologic Oncology Group, including the GOG-87B trial, for example. These chemotherapy studies have documented some antitumor activity for cisplatin, doxorubicin, and ifosfamide. These studies have also documented differences in response leading to separate trials for patients with carcinosarcomas and leiomyosarcomas. As an example, in patients previously untreated with chemotherapy, ifosfamide had a 32.2% response rate in patients with carcinosarcomas, a 33% response rate in patients with endometrial stromal cell sarcomas, and a 17.2% partial response rate in patients with leiomyosarcomas. Doxorubicin in combination with dacarbazine or cyclophosphamide is no more active than doxorubicin alone for recurrent disease.[4,5] Cisplatin has activity as first-line therapy and minimal activity as second-line therapy for patients with carcinosarcomas, but cisplatin is inactive as first- or second-line therapy for patients with leiomyosarcomas.[6,7] A regimen of gemcitabine plus docetaxel had a 53% response rate in patients with unresectable leiomyosarcomas and is undergoing further study.
Endometrial cancer is a disease that primarily affects postmenopausal women at an average age of 60 years at diagnosis. Risk factors include postmenopausal estrogen therapy, obesity, a high-fat diet, reproductive factors like nulliparity, early menarche and late menopause, polycystic ovarian syndrome, and tamoxifen use. Women with hereditary nonpolyposis colorectal cancer syndrome have a markedly increased risk of endometrial cancer compared with women in the general population.
A randomized comparison that was seen in the GOG-108 trial, for example, of ifosfamide with or without cisplatin for first-line therapy for patients with measurable advanced or recurrent carcinosarcomas demonstrated a higher response rate (54% vs. 34%) and longer progression-free survival (PFS) on the combination arm (6 months vs. 4 months), but there was no significant improvement in survival (9 months vs. 8 months).[Level of evidence: 1iiA] The follow-up GOG-0161 [NCT00003128] study utilized 3-day ifosfamide regimens (instead of the more toxic 5-day regimen in the preceding study) for the control and for a combination with paclitaxel (with filgrastim starting on day 4). The combination was superior in response rates (45% vs. 29%), PFS (8.4 months vs. 5.8 months), and overall survival (13.5 months and 8.4 months). The hazard ratio for death favored the combination 0.69 (95% confidence interval, 0.49–0.97).[Level of evidence: 1iiA] In this study, 52% of 179 evaluable patients had recurrent disease, 18% had stage III disease, and 30% had stage IV disease. In addition, imbalances were present in the sites of disease and in the use of prior radiation therapy, and 30 patients were excluded for wrong pathology.