A phase II evaluation of weekly docetaxel in the treatment of recurrent or persistent endometrial carcinoma: A study by the Gynecologic Oncology Group

doi:10.1016/j.ygyno.2008.06.013

Gynecologic Oncology

Volume 111, Issue 1, October 2008, Pages 22-26

https://doi.org/10.1016/j.ygyno.2008.06.013 Get rights and content

Abstract

Objective

A phase II study was conducted to evaluate the anti-tumor activity and adverse effects of weekly docetaxel in patients with previously treated endometrial cancer.

Methods

Eligible patients were to have measurable disease with no more than one prior chemotherapy regimen. Docetaxel 36 mg/m² was administered intravenously over 1 h on days 1, 8 and 15. Cycles were repeated every 28 days until progression of disease or adverse effects prohibited further therapy.

Results

Twenty-seven patients were entered onto this study, of whom 26 were eligible and evaluable. All patients had received prior platinum with twenty (76.9%) having received prior treatment with paclitaxel. There were two (7.7%) partial responses, eight patients (30.8%) with stable disease, and fourteen patients (53.8%) with increasing disease. The most frequently reported adverse events were leucopenia, neutropenia, gastrointestinal, constitutional and peripheral neuropathy. Grade 3 and 4 adverse events were uncommon.

Conclusions

Docetaxel, at the dose and schedule tested, has modest activity in this patient population.

Introduction

Endometrial cancer is the most common gynecologic cancer. In the United States there will be approximately 39,000 new cases and 7400 deaths from endometrial cancer in 2007 [1]. Compared to other gynecologic cancers, endometrial cancer has a relatively good prognosis due to the high frequency of non-metastatic disease (90%) at presentation. However, approximately 10% of patients with endometrial cancer are diagnosed with metastatic disease. The prognosis of these women, as well as those that recur after initial therapy, is poor.

The first line treatment for patients with low grade tumors is frequently hormonal agents, while those with higher grade tumors or those that fail hormonal therapy are candidates for cytotoxic drugs. Several chemotherapy agents have shown activity in endometrial carcinoma with doxorubicin, cisplatin and paclitaxel among the most active agents [2], [3], [4], [5].

Docetaxel (Taxotere) is a taxoid agent derived from 10-deacetylbaccatin III, a compound extracted from the European yew, Taxus baccata[6]. It has significant activity in a variety of solid tumors, including breast and ovarian cancer [7], [8]. Of particular importance, a response rate of approximately 20% has been suggested in patients with paclitaxel-resistant breast and ovarian carcinoma [9], [10]. In metastatic breast cancer a trend towards improvement in time to tumor progression and a significant dose–response relationship were observed for docetaxel [11].

The activity of docetaxel in endometrial cancer has been reported in 2 clinical trials. Katsumata et al. evaluated the activity of docetaxel at a dose of 70 mg/m² every 3 weeks and reported an overall response rate of 31% [12]. Using weekly docetaxel at 35 mg/m², Günthert reported a response rate of 21% in previously untreated endometrial cancer [13].

Based on these data, the Gynecologic Oncology Group (GOG) decided to perform a phase II clinical trial of docetaxel in previously treated endometrial cancers. We selected a schedule of weekly administration at dose of 36 mg/m² with the intent of maintaining dose intensity while minimizing myelosuppression. This dose was identified as the maximal tolerated dose in phase I studies and was shown to be safe and active in metastatic breast cancer [14], [15].

Section snippets

Patients

The patients had to have histological evidence of primary and recurrent or persistent endometrial carcinoma with measurable disease and at least one target lesion by RECIST (Response Evaluation Criteria in Solid Tumors) criteria. Pathological material had to be available for central review by the Pathology Committee of the GOG. Patients required prior treatment with one chemotherapeutic regimen for management of endometrial carcinoma. Patients were allowed, but not required, to receive one

Patient characteristics

The study was activated in July 2004 and was closed to accrual in April 2005. A total of 27 patients were enrolled (Table 1). One patient was ineligible due to inadequate pathology materials, did not receive treatment and was therefore excluded from safety and efficacy analysis.

Tumor response

Of the 26 patients, two (7.7%) achieved an objective response rate, all of them PR. Eight patients (30.8%) had stable disease, and fourteen patients (53.8%) had increasing disease. Response could not be assessed in two

Discussion

Most women with endometrial cancer are diagnosed with early disease and have an excellent 5 year survival. However, more than 7000 women succumb annually from advanced or recurrent disease. Treatment with cytotoxic chemotherapy is frequently used in this group. The most active agents are cisplatin, doxorubicin and paclitaxel. In most randomized trials combination chemotherapy has not improved overall survival [17], [18]. A noteworthy exception is the addition of paclitaxel to cisplatin and

Conflict of interest statement

The authors declare that there are no conflicts of interest with the exception of Dr. Garcia who would like to report that he is on the Speakers Bureau for Eli Lilly, Pfizer.

Acknowledgments

This study was supported by National Cancer Institute grants to the Gynecologic Oncology Group Administrative Office (CA 27469) and the Gynecologic Oncology Group Statistical Office (CA 37517).

Duke University Medical Center, Abington Memorial Hospital, University of Washington, University of North Carolina, University of Iowa Hospitals and Clinics, Walter Reed Army Medical Center, University of Minnesota Medical School, University of Iowa Hospitals and Clinics, Tufts-New England Medical Center,

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A phase II evaluation of weekly docetaxel in the treatment of recurrent or persistent endometrial carcinoma: A study by the Gynecologic Oncology Group

Abstract

Objective

Methods

Results

Conclusions

Introduction

Section snippets

Patients

Patient characteristics

Tumor response

Discussion

Conflict of interest statement

Acknowledgments

Gynecol. Oncol.

Gynecol. Oncol.

Gynecol. Oncol.

Ann. Oncol.

Gynecol. Oncol.

Gynecol. Oncol.

Gynecol. Oncol.

Cancer Statistics, 2007

CA Cancer J. Clin.

Phase II study of adriamycin in the treatment of advanced or recurrent endometrial carcinoma: a Gynecologic Oncology Group Study

Cancer Treat. Rep.

Phase II trial of cisplatin as second line chemotherapy in patients with advanced or recurrent endometrial carcinoma: a Gynecologic Oncology Group Study

Am. J. Clin. Oncol.

Phase II trial of cisplatin as first line chemotherapy in patients with advanced or recurrent endometrial carcinoma: a Gynecologic Oncology Group study

Gynecol. Oncol.

Docetaxel

J. Clin. Oncol.