Adjuvant chemotherapy and radiation for endometrial cancer – pro

Adjuvant chemo is standard for adjuvant therapy of endometrial cancer. There is no evidence of benefit to support the use of adjuvant therapy for low and low-intermediate risk groups. The adjuvant medical therapy of endometrial cancer remains poorly investigated but seems only worthy of consideration in high risk patients. A systematic review and meta-analysis of the Cochrane Collaboration revealed that the adjuvant use of progestational agents may indeed be dangerous. They do not significantly reduce the risk of recurrence and endometrial cancer-related death, but significantly increase the risk of non-cancer-related death. Numerous small trials have investigated the efficacy of adjuvant chemotherapy in endometrial cancer, but were not adequately powered to detect a difference in survival. Adjuvant chemotherapy with doxorubicin and cisplatin has been compared with whole abdominal radiation therapy in stage III and IV disease, and chemotherapy turned out to be superior to radiotherapy with regards to progression-free (hazard ratio 0.81) and overall survival (hazard ratio 0.71; P < 0.05). Taxol/carboplatin/adriamycin is more toxic and it is not known whether it is as effective. NCCN says that it is subject of current studies but still lists it for stage II and III. GOG trial 209 is assessing Taxol/carboplatin vs. Taxol/carboplatin/adriamycin in a randomized trial.

Data from randomized studies such as PORTEC-1 (Postoperative Radiation Therapy in Endometrial Carcinoma), the GOG-99 (Gynecologic Oncology Group) and the recent ASTEC/EN.5 trial have shown a reduction in locoregional disease recurrence but not benefit in overall survival. Those studies have shown that the majority of the initial recurrences for patients with disease limited to the uterus were limited to the vagina, suggesting that vaginal vault brachytherapy alone could be used as an adjuvant treatment. To compare adjuvant pelvic RT with vaginal BT alone in uterine-confined disease, the PORTEC-2 study randomized patients between those two modalities and showed very satisfactory vaginal and pelvic control rates and equal survival with both modalities.

Another option under discussion is chemoradiation. In the EORTC 55991 trial (abstract only), patients with stages I, II, IIIA (positive cytology only), and IIIC (excluding para-aortic metastases) and clear, serous, and anaplastic cell types were enrolled. Most patients had two or more risk factors including G3, deep myometrial invasion, or DNA nondiploidy. Enrolled patients were randomized to RT (EBRT ± VBT) or combined chemoradiotherapy. The chemotherapy regimen before August 2004 was cisplatin-doxorubicin or -epirubicin; thereafter, it was changed to cisplatin-doxorubicin or -epirubicin, paclitaxel-epirubicin-carboplatin, or paclitaxel- carboplatin. The hazard ratio for PFS was 0.58 in favor of the combined chemoradiotherapy group, and a 7% difference in estimated 5-year PFS was found. There is also an ongoing PORTEC-3 trial in which high-intermediate and high risk patients (stage IB with LVSI and G3, stage II and G3, stage IIIA or IIIC, and stage IB-III and serous or clear cell type) were randomized to pelvic EBRT (48.6 Gy) alone or concurrent chemoradiotherapy (EBRT and two courses of cisplatin) followed by adjuvant CT (carboplatin and paclitaxel for four courses). Results are awaited. Additionally, there is an ongoing GOG 258 trial in which patients (stages I and II with serous or clear cell type and positive cytology, stage III-IVA) were randomized to receive carboplatin and paclitaxel for six courses or concurrent chemoradiotherapy (EBRT ± VBT and two courses of cisplatin) followed by four courses of carboplatin and paclitaxel

Randall ME, Filiaci VL, Muss H, et al. Randomized phase III trial of whole-abdominal irradiation versus doxorubicin and cisplatin chemotherapy in advanced endometrial carcinoma: A Gynecologic Oncology Group Study. Journal of Clinical Oncology . 2006;24:36-44.

Sheng-Mou Hsiao and Lin-Hung Wei Controversies in the Adjuvant Therapy of Endometrial Cancer ISRN Obstetrics and Gynecology Volume 2011 (2011), Article ID 724649

T Dell’Anna, A Buda, I Floriani Adjuvant chemotherapy for endometrial cancer Cochrane Database of Systematic Reviews 2008 Issue 1, endometrial cancer, ENDO-5 and ENDO-B, 2012

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