Systemic chemotherapy for uterine carcinoma: Metastatic and adjuvant

Endometrial carcinoma is a chemotherapy-sensitive tumor. Taxanes, platinum agents, and anthracyclines are generally active in chemotherapy-naive patients. The benefit to chemotherapy in recurrent or metastatic disease is modest, and toxicities need to be aggressively managed in this elderly population. Good evidence (although not unanimous evidence) exists for the benefit of chemotherapy in stage III cancers of endometrioid and serous histology. The optimal way to combine chemotherapy with radiotherapy is not known. Women with stage III carcinomas are currently eligible for GOG 209, which is available on the Cancer Trials Support Unit Web site and compares carboplatin/paclitaxel with paclitaxel/cisplatin/doxorubicin; on this trial, radiotherapy, if administered, is administered before random assignment. To date, there is no clinical trial evidence for the benefit of treating earlier stages of disease with chemotherapy, and treatment decisions must be individualized. It is possible that the benefits of chemotherapy for a woman with a given histology and grade of disease are a function of the risk of recurrence. At this time, it is reasonable, after discussion of risks, benefits, and uncertainties, to consider adjuvant chemotherapy in healthy women with deeply invasive stage I serous or clear cell uterine carcinomas. Clear cell carcinomas of the uterus are included in this group because they are a higher risk histology and because they are uncommon enough that mere may never be good evidence about their chemotherapy sensitivity. The value of adjuvant chemotherapy for deeply invasive grade 3 endometrioid carcinoma is not yet known, although it is anticipated that future studies will address this important question. The benefit of adjuvant chemotherapy for any stage of carcinosarcoma remains uncertain; the ifosfamide/cisplatin regimen reported by Wolfson et al80 is fairly aggressive, and this study has been published in abstract form only. Because the likelihood of systemic spread of serous carcinomas is so high, it is also reasonable to offer chemotherapy to all healthy women with serous carcinomas of the uterus who have not been fully surgically staged. However, the risk of recurrence of thoroughly staged stage IA and IB serous carcinomas is similar to that of stage IA and IB clear cell or grade 3 endometrioid carcinomas, and chemotherapy may represent overtreatment in many of these patients. In particular, women with small-volume serous carcinomas who have no disease found in the hysterectomy specimen (because it was all removed during diagnostic procedures) seem to do well with no adjuvant therapy and can be followed with observation only.81,82 Enrollment of women with endometrial carcinoma on clinical trials, when available, must remain a priority so we can make better-informed recommendations to our patients in the future. © 2007 by American Society of Clinical Oncology.