52-year-old female with a diagnosis of stage IIIC Grade 3 endometrial cancer. Following the adequate surgery she was started on a chemotherapy protocol, including Taxol, Epirubicin and Cisplatinum. However the first course caused severe toxicity and was switched to Taxol and carboplatinum. One treatment option is by intense combination chemotherapy, and therefore the expert supports the protocol used by this case. Another option is endocrine manipulation by hormone therapy.
1. Treatment options
2. Open clinical trials.
This is a 52 years old female with a diagnosis of endometrial cancer. According to the medical information the Stage of the patient is IIIC Grade 3. Following the adequate surgery she was started on a chemotherapy protocol, including Taxol, Epirubicin and Cisplatinum. However the first course caused severe toxicity and was switched to Taxol and carboplatinum.
Several randomized trials by the Gynecologic Oncology Group have utilized the known antitumor activity of doxorubicin. The addition of cisplatin to doxorubicin increased response rates and progression-free survival (PFS) over doxorubicin alone but without an effect on overall survival (OS).1 However, in a trial conducted in a subset of patients with stage III or IV disease with residual tumors smaller than 2 cm and no parenchymal organ involvement, the use of the combination of cisplatin and doxorubicin resulted in improved OS compared to whole-abdominal radiation therapy (5-year survival rates of 55% vs. 42%).2 In a subsequent trial, paclitaxel with doxorubicin had a similar outcome to cisplatin with doxorubicin.3-4 The three-drug regimen (doxorubicin, cisplatin, and paclitaxel) with granulocyte colony-stimulating factor, however, was significantly superior to cisplatin plus doxorubicin: response rates were 57% versus 34%, PFS was 8.3 months versus 5.3 months, and OS was 15.3 months versus 12.3 months, respectively. The superior regimen was associated with a 12% grade 3 and a 27% grade 2 peripheral neuropathy. 3-4
A recent Cochrane review of chemotherapy treatment for advanced endometrial cancer showed that more intense combination chemotherapy significantly improves the disease-free survival and the data indicate a modest improvement in OS.5 The addition of anthracyclines (e.g. doxorubicin) or the taxanes [e.g. paclitaxel (Taxol)] to cisplatin increases the response rate. More intensive regimens are associated with the gain in survival. However, grade 3 and 4 myelosuppression and gastrointestinal toxicity are also increased. While no one drug or regimen offers a clear benefit for women with advanced endometrial cancer, platinum drugs, anthracyclines and paclitaxel seem the most promising agents. The question is if the modest survival gain of the order of 3 months justifies the toxicity of a three-drug combination in this individual patient. The optimum chemotherapy regimen to be used is not established, but there is wide experience in other tumors with the use of carboplatin and paclitaxel together, as used in this patient. Therefore I support the protocol used by her doctors.
Another option is the endocrine manipulation. The majority of studies have employed oral progestogens, including medroxyprogesterone acetate (MPA) and megestrol acetate, which have response rates in the range of 11–56%.6 Although the majority of responses to hormone therapy are relatively short in duration, occasional patients remain free from disease progression for more than 12 months. The relative lack of side effects of progestogens compared to cytotoxic chemotherapy initially led to their widespread use in unselected patient populations, but fluid retention, weight gain, dyspnea, and thromboembolic events can be a problem in a small proportion of cases. In recent years, their use has been often confined to the better differentiated cases, which usually correspond with those demonstrating estrogen receptor (ER) and progesterone receptor (PR), while more aggressive tumors are more likely to be given chemotherapy. Therefore I would suggest examining the receptor status of the tumor. However, receptor-negative status should not be an absolute contraindication to hormone intervention. Integration of the hormone treatment with conventional chemotherapy is still equivocal.
Patients with advanced endometrial cancer are candidates for clinical trials. I am not aware to such an open trial.
At this point I do not have any further suggestions for treatment.
1. Thigpen JT, Brady MF, Homesley HD, et al.: Phase III trial of doxorubicin with or without cisplatin in advanced endometrial carcinoma: a Gynecologic Oncology Group study. J Clin Oncol 22 (19): 3902-8, 2004.
2. 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. J Clin Oncol 24 (1): 36-44, 2006.
3. Fleming GF, Brunetto VL, Cella D, et al.: Phase III trial of doxorubicin plus cisplatin with or without paclitaxel plus filgrastim in advanced endometrial carcinoma: a Gynecologic Oncology Group Study. J Clin Oncol 22 (11): 2159-66, 2004.
4. Fleming GF, Filiaci VL, Bentley RC, et al.: Phase III randomized trial of doxorubicin + cisplatin versus doxorubicin + 24-h paclitaxel + filgrastim in endometrial carcinoma: a Gynecologic Oncology Group study. Ann Oncol 15 (8): 1173-8, 2004.
5. Humber CE, Tierney JF, Symonds RP, Collingwood M, Kirwan J, Williams C, Green JA. Chemotherapy for advanced, recurrent or metastatic endometrial cancer: a systematic review of Cochrane collaboration. Ann Oncol. 2007 18(3):409-20
6. Decruze SB, Green JA. Hormone therapy in advanced and recurrent endometrial cancer: a systematic review. Int J Gynecol Cancer. 2007 Sep-Oct;17(5):964-78.