Cancer Treatment

Adjuvant chemotherapy for endometrial cancer

Adjuvant chemo is standard for adjuvant therapy of endometrial cancer. Less clear is the setting and the drugs that should be used.

The role of adjuvant radiation therapy has been defined much more clearly in recent years, at least for patients with stage I and very early stage II disease. Pelvic radiation therapy dramatically reduced the risk of locoregional recurrence in three randomised controlled trials, regardless of whether or not retroperitoneal lymphadenectomy was part of the standard surgical procedure. None of these trials revealed a significant beneficial effect of radiotherapy on survival.

The adjuvant medical therapy of endometrial cancer remains poorly investigated. 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 mote toxic and it is not known whether it is as effective.

GOG trial 209 is assessing Taxol/carboplatin vs. Taxol/carboplatin/adriamycin in a randomized trial.

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.

T Dell'Anna, A Buda, I Floriani Adjuvant chemotherapy for endometrial cancer

Cochrane Database of Systematic Reviews 2008 Issue 1

nccn.org, endometrial cancer

PET for endometrial cancer

Lay Summary: Not much is known about PET scans in endometrial cancer. The bladder can interfere with visualizing the uterus.

PET scan is not routine in endometrial cancer, either for diagnosis, staging or restaging.Evaluation of endometrial cancer is not currently an approved indication by CMS (Center for Medicare Services) for reimbursement for FDG-PET studies in the United States. Information on the application of FDG-PET in the assessment of endometrial cancer is very limited in the literature at present. It has been shown that endometrial cancer is generally highly FDG-avid and that it is feasible to detect the primary tumor, as well as regional nodal and distant metastases, with FDG-PET As with other types of malignancies, FDG-PET is unable to detect small tumor volumes, and the sensitivity of tumor detection by FDG-PET is reduced in poorly controlled hyperglycemia. The intense activity of FDG excreted in the urinary bladder may impair visualization of adjacent FDG-avid disease, such as primary endometrial cancer or locoregional nodal metastases. Bladder irrigation has been suggested as one method of overcoming this potential problem.

Berman ML, McHale MT. Uterus. In: Haskell CM, Berek JS, eds. Cancer Treatment. 5th ed. Philadelphia: W.B. Saunders; 2001:951-966.
Nakahara T, Fujii H, Ide M, et al. F-18 FDG uptake in endometrial cancer. Clin Nucl Med. 2001;26:82-83. Abstract
Torizuka T, Toshihiko K, Futasubashi M, et al. Imaging of gynecologic tumors: comparison of 11-C-Choline PET with 18F-FDG PET. J Nucl Med. 2003;44:1051-1056. Abstract
Koyama K, Okamura T, Kawabe J, et al. Evaluation of 18F-FDG PET with bladder irrigation in patients with uterine and ovarian tumors. J Nucl Med. 2003;44:353-358

Standard chemotherapy for endometrial cancer

Lay Summary: Adjuvant chemo is standard for endometrial cancer and has a limited role for metastatic disease.

There is currently little hope for cure in patients with metastatic endometrial carcinoma. Selected patients will respond to hormonal therapy, particularly progestins; however, for most women with advanced disease, chemotherapy is currently the standard antineoplastic treatment option. Taxanes, anthracyclines, and platinum compounds represent the chemotherapeutic agents with the greatest activity in this disease. Response rates (RRs) for each agent range from 20% to 35%. The combination of doxorubicin plus cisplatin (AP) has produced RRs of 40% to 46%, with reported median progression-free survival (PFS) ranging from 5.2 to 7.2 months in the three most recent Gynecologic Oncology Group (GOG) randomized trials. Most recently, the GOG compared AP with doxorubicin plus paclitaxel 150 mg/m2 as a 24-hour continuous infusion with filgrastim support, and there was no statistically significant improvement in objective RR, PFS, or overall survival (OS) between the regimens. The most recent randomized study found that TAP significantly improves RR, PFS, and OS compared with AP.

In 2001, the GOG published the results of a dose-finding trial that combined cisplatin, doxorubicin, and a 3-hour infusion of paclitaxel (TAP) in chemotherapy-naïve patients with advanced endometrial carcinoma and other gynecologic malignancies.11 In that trial, doxorubicin and cisplatin were administered on day 1, and paclitaxel, on day 2 because of previous reports suggesting that the cardiotoxicity associated with the paclitaxel + doxorubicin combination was decreased when these agents were administered 16 to 24 hours apart.12 Even when low doses of the combination of TAP were used, filgrastim was required for hematopoietic support, and neurotoxicity became the dose-limiting toxicity. The recommended phase II doses were doxorubicin 45 mg/m2, cisplatin 60 mg/m2, and paclitaxel 160 mg/m2 intravenously over 3 hours, with filgrastim 5 µg/kg given on days 3 to 12. Of 20 patients treated at this dose level, two (10%) developed grade 3 peripheral neuropathy

The NCCN lists carboplatin, cisplatin and palcitaxel as options for metastatic or advanced endometrial carcinoma, as single agents or combined. For clinical use, carboplatin is interchangeable with cisplatin by general consensus because of their similarity and trial evidence in a a number of cancer sites (although not in all and not in endometrial cancer).

Both carboplatin/paclitaxel and adriamycin/cisplatin/paclitaxel can be considered standard of care. The ongoing Phase III trial is to define the better regimen.

Gini F. Fleming, Virginia L. Brunetto, David Cella, Katherine Y. Look, Gary C. Reid, Adnan R. Munkarah, Richard Kline, Robert A. Burger, Annekathryn Goodman, R. Tucker Burks Phase III Trial of Doxorubicin Plus Cisplatin With or Without Paclitaxel Plus Filgrastim in Advanced Endometrial Carcinoma: A Gynecologic Oncology Group Study Oncology, Vol 22, No 11 (June 1), 2004: pp. 2159-2166

J. T. Thigpen, M. F. Brady, H. D. Homesley, J. Malfetano, B. DuBeshter, R. A. Burger, and S. Liao Phase III Trial of Doxorubicin With or Without Cisplatin in Advanced Endometrial Carcinoma: A Gynecologic Oncology Group Study
J. Clin. Oncol., October 1, 2004; 22(19): 3902 - 3908.

G. F. Fleming, V. L. Filiaci, R. C. Bentley, T. Herzog, J. Sorosky, L. Vaccarello, and H. Gallion
Phase III randomized trial of doxorubicin + cisplatin versus doxorubicin + 24-h paclitaxel + filgrastim in endometrial carcinoma: a Gynecologic Oncology Group study
Ann. Onc., August 1, 2004; 15(8): 1173 - 1178