Treating Endometrial Adenocarcinoma— Do Data Support the Use of Pegylated Liposomal Doxorubicin?

US Oncology & Hematology, 2011;7(1):58-60

Abstract:

Most women who are diagnosed with endometrial carcinoma present at an early stage and are usually cured of their disease by surgery with or without adjuvant radiation therapy and/or chemotherapy. For those patients who present with advanced disease or develop recurrent disease, survival is greatly diminished. Chemotherapy plays an important role in the management of these patients. Doxorubicin is one of the most active chemotherapy drugs in the advanced or recurrent setting, with response rates in the order of 25%. The use of doxorubicin is limited by its cumulative dose-dependent cardiotoxicity. Pegylated liposomal doxorubicin is a newer formulation of conventional doxorubicin. Its altered pharmacokinetics result in a longer half-life, decreased exposure in healthy tissues, and enhanced delivery of the active drug to the tumor bed. Pegylated liposomal doxorubicin has a relatively milder toxicity profile and a lower incidence of cardiac adverse events. In this article the data on the use of pegylated liposomal doxorubicin in advanced or recurrent endometrial cancer, including the serous papillary histologic variant, are reviewed.
Keywords: Endometrial cancer, uterine serous papillary cancer (USPC), advanced, recurrent, chemotherapy, doxorubicin, pegylated liposomal doxorubicin (PLD), cardiotoxicity
Disclosure: Bachir J Sakr, MD, has no conflicts of interest to declare. Don S Dizon, MD, consults for and was formerly on the speaker’s bureau of Ortho-Biotech.
Received: March 18, 2010 Accepted February 22, 2011 Citation US Oncology & Hematology, 2011;7(1):58-60
Correspondence: Bachir J Sakr, MD, Women & Infants’ Hospital, 101 Dudley Street, Providence, RI 02905. E: bjsakr@wihri.org

Endometrial carcinoma is the most common malignancy of the female genital tract, accounting for more than 42,000 cases annually in the US (6% of new cancer cases).1 Worldwide, it is the seventh most common cancer in women, with over 200,000 cases annually.2 Fortunately, most women present with dysfunctional vaginal bleeding or spotting—an early sign of endometrial pathology—and ultimately will be cured with surgical therapy. Unfortunately, more than 7,500 die of advanced or recurrent endometrial carcinoma every year.1 Endometrial carcinomas are classified as type I or type II.3,4 Type I tumors evolve in an estrogenrelated manner, are associated with endometrial hyperplasia, and express steroid hormone receptors. The usual pathologic phenotype is an endometrioid adenocarcinoma, which tends to be well differentiated and of low grade. By contrast, type II tumors—classically characterized as serous or clear-cell carcinomas—arise in atrophic endometrium in a manner unrelated to estrogen exposure. These tumors are usually negative or weakly positive for steroid hormone receptors, and are typically poorly differentiated and of high grade. In general, type II tumors are characterized by a more aggressive clinical course than type I tumors.3

The current treatment of endometrial carcinomas requires multimodal therapy and depends on the stage at presentation, histologic grade, and type. Surgery alone or with radiation therapy, chemotherapy, or endocrine therapy are all utilized in the front-line management of this disease. For women presenting with high-risk features (serous or clear cell, grade 3, deeply invasive to the myometrium, and nodal involvement), a combination of surgical staging followed by chemotherapy with or without radiation therapy is often employed.
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Keywords: Endometrial cancer, uterine serous papillary cancer (USPC), advanced, recurrent, chemotherapy, doxorubicin, pegylated liposomal doxorubicin (PLD), cardiotoxicity