Elsevier

Gynecologic Oncology

Volume 96, Issue 3, March 2005, Pages 630-634
Gynecologic Oncology

Adjuvant ifosfamide and cisplatin in patients with completely resected stage I or II carcinosarcomas (mixed mesodermal tumors) of the uterus: a Gynecologic Oncology Group study

https://doi.org/10.1016/j.ygyno.2004.11.022Get rights and content

Abstract

Objectives

To determine progression-free survival (PFS) and overall survival (OS) in women with completely resected stage I or II carcinosarcoma of the uterus treated with adjuvant ifosfamide and cisplatin, and to assess the toxicity of this regimen.

Methods

Eligible patients had histologically confirmed carcinosarcoma (mixed mesodermal tumor) and no postoperative radiotherapy following complete resection for clinical stage I or II disease. They were to have adequate renal, hepatic, and hematologic functions and performance status of 2 or less. Study entry was to be within 8 weeks of hysterectomy. Patients with previous chemotherapy, or other noncutaneous malignancies, were ineligible. Ifosfamide was administered 1.5 g/m2 intravenously (IV) over 1 h and cisplatin was given 20 mg/m2 over 15 min followed by mesna 120 mg/m2 IV bolus, then 1.5 g/m2/24 h as a continuous infusion. Initial doses (daily × 5 every 21 days × 3 cycles) were reduced by 20% (to 4 days) for myelotoxicity.

Results

Nine of seventy-six patients enrolled were deemed ineligible and another two who did not receive protocol treatment were inevaluable. Of the 65 evaluable patients, median age was 65 years; 50 patients (77%) were stage I and 15 (23%) were stage II. PFS and OS, respectively, were 69% and 82% at 24 months, and 54% and 52% at 84 months. Overall 5-year survival was 62%. Leukopenia was the most commonly reported, but manageable, toxicity.

Conclusion

Adjuvant ifosfamide and cisplatin after primary surgery for stage I or II carcinosarcoma of the uterus is tolerable. In the absence of concurrent controls, the impact on PFS and OS is unclear. Pelvic relapse remains problematic.

Introduction

Carcinosarcomas (a subcategory of mixed epithelial/non-epithelial uterine neoplasms also known as mixed mesodermal tumors) comprise 2–3% of malignancies of the uterus and account for 1000–1500 cases annually in the United States. These tumors occur in women with a median age of 62 years. Although approximately half are diagnosed with stage I or II, up to 50% of these early stage tumors recur and are fatal. Few patients with extrauterine disease at the time of diagnosis survive despite therapy. Most attention has been directed toward the development of palliative chemotherapy for patients with advanced or recurrent disease, and to postoperative adjuvant treatment in those with Stage I and II lesions.

Although adjuvant postoperative pelvic radiotherapy has been employed for these patients [1], [2], the high incidence of distant metastases has insured a continued interest in postoperative systemic chemotherapy. An early Gynecologic Oncology Group (GOG) study of adjuvant doxorubicin in uterine sarcomas was not encouraging [3]. The recognition of ifosfamide [4] and cisplatin [5] as highly active agents in patients with advanced or metastatic uterine carcinosarcomas suggested that these drugs should be evaluated in an adjuvant setting. This phase II trial was undertaken to determine progression-free survival (PFS) and overall survival (OS) in women with stage I–II carcinosarcoma of the uterus who were treated with three cycles of adjuvant cisplatin and ifosfamide.

Section snippets

Materials and methods

Patients with carcinosarcoma of the uterus were eligible for this study if review by the GOG Pathology Committee confirmed the histologic diagnosis and registration occurred within 8 weeks of hysterectomy. Although lymphadenectomy was not required, total abdominal hysterectomy and bilateral salpingo-oophorectomy were; disease had to be limited to the uterine corpus and cervix (clinical stage I and II). Patients could not have received postoperative radiotherapy and were to have adequate

Results

Between May 1991 and March 1993, 76 patients were entered onto this study. Nine were deemed ineligible, seven for the wrong cell type, and one each for wrong stage and having received protocol treatment prior to study entry. Two patients were inevaluable because they chose not to be treated, leaving 65 eligible and evaluable patients. Median age of these patients was 65 (range: 24–82) years; GOG PS was 0 in 34, 1 in 29, and 2 in two patients, respectively. Fifty patients (77%) were clinical

Discussion

Although hysterectomy may be curative in a small proportion of patients with early carcinosarcomas of the uterus, treatment of these sarcomas has been largely unsuccessful. Reported 5-year survival rates in stage I disease seldom exceed 50% [6]. Gerszten et al. [1] advocated postoperative radiotherapy, noting a reduction in postoperative pelvic recurrences from 55% in 31 patients treated with surgery alone to 3% (1 patient) among 29 who received radiation. Median survival times for the two

Acknowledgments

This study was supported by National Cancer Institute grants of the Gynecologic Oncology Group Administrative Office (CA 27469) and the Gynecologic Oncology Group Statistical Office (CA 37517). The following Gynecologic Oncology Group institutions participated in this study: Oregon Health Sciences University, Duke University Medical Center, Abington Memorial Hospital, Walter Reed Army Medical Center, Wayne State University School of Medicine, University of Minnesota Medical School, University

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1

Current address: University of Iowa Hospitals and Clinics, Iowa City, IA, USA.

2

Current address: OB/GYN Department, Leo Jenkins Cancer Center, Greenville, NC, USA.

3

Current address: OB/GYN Department, Magee Women's Hospital/University of Pittsburgh, Pittsburgh, PA, USA; and Precision Therapeutics, Pittsburgh, PA, USA.

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