Combination Chemotherapy for Endometrial and Cervical Adenocarcinoma
ABSTRACT & COMMENTARY
Synopsis: A combination of epirubicin, paclitaxel, and cisplatin produced a clinical response rate of 73% and a complete response rate of 23% in 49 patients with endometrial or cervical adenocarcinoma.
Source: Lissoni A, et al. Ann Oncol 1997;8:969-972.
Uterine adenocarcinomas occur in two varieties. Endometrial cancer, the most common invasive malignancy of the female genital tract in developed countries, occurs in the uterine corpus. In addition, about 5-15% of cervical carcinomas are adenocarcinomas rather than squamous cell carcinomas, and the adenocarcinomas seem to have a worse prognosis than squamous cell tumors of similar stage, particularly in locally advanced disease. Both of these tumors are derived embryologically from Mullerian epithelium; however, the cause of each appears to be distinct. Hormonal influences dominate the etiologic factors in endometrial cancers; human papillomavirus infection is the dominant risk factor for cervical cancer.
Systemic chemotherapy for uterine adenocarcinoma is only modestly effective. Cisplatin and doxorubicin are commonly used in combination and may produce responses in about one-third of patients. Recent studies have suggested that paclitaxel may be highly active in uterine adenocarcinoma. Ball and colleagues reported a 36% overall response rate with single agent paclitaxel in patients with endometrial carcinoma that recurred after local therapy.1 Lissoni and colleagues reported a 37% response rate from single agent paclitaxel in patients with endometrial adenocarcinoma who progressed on cisplatin plus an anthracycline.2 This promising single agent activity prompted Lissoni and associates to integrate paclitaxel into a combination regimen including cisplatin and an anthracycline.
The regimen consisted of epirubicin given at 70 mg/m2 followed by paclitaxel at 175 mg/m2 given over three hours and cisplatin at 50 mg/m2. This CEP regimen was repeated every three weeks. Forty-nine patients were treated; 30 with endometrial primaries (10 stage III, 7 stage IV, and 10 with recurrent disease after radiation therapy) and 19 with cervical primaries (14 with poor prognosis IB disease, 2 with stage IV disease, and 2 with recurrence).
The overall clinical response rate in the patients with endometrial cancer was 73% with 23% complete responses. In patients with metastatic disease, the response rate was 86% with a median response duration of seven months (range, 2-12+). In the patients with cervical adenocarcinoma, the clinical response rate was 53%, and 16% of the patients had no residual disease. The patients with stage IB disease who received the chemotherapy before a definitive surgical procedure had a 64% response rate. The median duration of response to chemotherapy was 9+ months (range, 3 ± 12).
The main toxicity was myelotoxicity, grade 3 in 61%. There was one treatment-related death, and one patient developed acute congestive heart failure after the third cycle of therapy. Mucositis developed in 23% of patients. Grade 1 peripheral neuropathy was noted in 46% of patients. Overall, the therapy was well-tolerated.
COMMENTARY
The remarkable efficacy of the CEP regimen and its acceptable level of toxicity make it an attractive candidate for evaluation in neoadjuvant treatment schemes. Furthermore, it should be examined prospectively in comparison to cisplatin plus doxorubicin, the standard combination regimen employed in this setting. It is not clear whether CEP might sufficiently reduce tumor burden to the point where subsequent surgery or radiation therapy might result in cured patients.
This is the first report suggesting that a paclitaxel-containing combination chemotherapy program may be active in cervical adenocarcinoma. In the 14 patients who received the chemotherapy in a neoadjuvant setting, a 62% pathological response rate was noted, with 6% of treated patients being histologically free of disease at surgery and another 12% having only microscopic residual tumor. These results make the CEP regimen worthy of consideration as primary treatment for patients with advanced disease.
References
1. Ball HG, et al. Gynecol Oncol 1996;62:278-281.
2. Lissoni A, et al. Ann Oncol 1996;7:861-863.
In patients with endometrial adenocarcinoma who progressed on cisplatin plus an anthracycline, Lissoni and colleagues reported that the response rate from single agent paclitaxel was:
a. 37%.
b. 50%.
c. 18%.
d. 4%.
e. 22%.
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