Clinical benefit of trabectedin in uterine adenosarcoma
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SHORT COMMUNICATION
Clinical benefit of trabectedin in uterine adenosarcoma Brett A. Schroeder • Eve T. Rodler • Elizabeth T. Loggers • Seth M. Pollack Robin L. Jones
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Received: 28 January 2013 / Accepted: 6 February 2013 / Published online: 28 February 2013 Ó Springer Science+Business Media New York 2013
Abstract Uterine adenosarcoma is an extremely rare uterine malignancy, and the utility of chemotherapy in this disease is not well defined. This study assessed the safety and efficacy of trabectedin in patients with recurrent/ metastatic uterine adenosarcoma with sarcomatous overgrowth. A retrospective search of a prospectively maintained database was performed to identify patients with adenosarcoma treated with trabectedin between 2010 and 2012, within a compassionate use trial. Three patients with recurrent/metastatic uterine adenosarcoma treated with trabectedin were identified. All three patients tolerated the drug well. Two patients obtained prolonged clinical benefit from treatment, one having received 17 cycles and another 11 cycles of therapy. Trabectedin is well tolerated and has clinical activity in recurrent/metastatic uterine adenosarcoma. Keywords Uterine adenosarcoma Systemic therapy Trabectedin Clinical benefit
Background Uterine adenosarcoma is a very rare malignancy originally described by Clement and Scully in 1974 [1]. This tumor typically affects postmenopausal women, with a median age of 57 years [1–3]. Total abdominal hysterectomy and bilateral salpingoophorectomy (TAH–BSO) is the mainstay of management of localized disease [1]. Uterine adenosarcoma
B. A. Schroeder E. T. Rodler E. T. Loggers S. M. Pollack R. L. Jones (&) Fred Hutchinson Cancer Research Center, University of Washington, 825 Eastlake Avenue East, Seattle, WA, USA e-mail: [email protected]
is characterized by benign or occasionally atypical glands and a malignant (sarcomatous) stroma [1]. This disease is generally considered as being of low malignant potential, with local vaginal, pelvic or abdominal recurrences seen in approximately 25 % of cases [4]. However, some patients may have aggressive disease with poor outcome [3]. The role of systemic chemotherapy in patients with recurrent or metastatic disease is not well defined, with the literature limited to case reports [5–7]. Trabectedin is a synthetically produced alkaloid, originally derived from the Caribbean marine tunicate Ecteinascidia turbinate [8]. A number of potential mechanisms of action have been suggested for this drug, including binding to the DNA minor groove and consequently distorting DNA and inhibiting transcription, resulting in disruption of the cell cycle and inhibition of proliferation. Three Phase II trials showed that trabectedin has activity in soft tissue sarcoma patients resistant to anthracycline and ifosfamide, with a high proportion of patients achieving clinical benefit, with disease stabilization in up to 60 % of patients with leiomyosarcoma and synovial sarcoma [9–11]. A Phase II trial randomized liposarcoma and leiomyo
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