Patients cured of gestational trophoblastic tumors using modern chemotherapy regimens have no overall increased risk of subsequent malignancy, according to findings from a review of nearly 2,000 patients treated at a single institution.

There is evidence, however, of an increased risk of leukemia in patients treated with etoposide, methotrexate, and dactinomycin followed by cyclophosphamide and vincristine (EMA-CO) on alternating weeks, of other site-specific malignancies in small numbers of patients, and of early menopause with most regimens, Dr. Philip Savage of Charing Cross Hospital, London, and his colleagues reported online Dec. 29 in the Journal of Clinical Oncology.

Of 1,903 patients treated between 1958 and 2000 with a mean follow-up of 16.9 years, 86 developed a subsequent malignancy, compared with the expected number of 79, based on a national age-matched population (standardized incidence ratio, 1.1). The risk was low among those treated with EMA-CO (standardized incidence ratio, 0.9), as well as among those treated with methotrexate and folinic acid (MTX-FA; standardized incidence ratio, 0.7), but was slightly higher when these two regimens were used with other nonalkylating agents and with other combination regimens including alkylating agents or cisplatin (standardized incidence ratios ranged from 1.4 to 1.9). The risk also increased with increasing numbers of chemotherapy cycles (standardized incidence ratio for 7-12 cycles, 1.4, and for 13 or more cycles, 2.5), the investigators said (J. Clin. Oncol. 2014 Dec. 29 [ doi:10.1200/JCO.2014.57.5332 ]).

Leukemia occurred in six patients, including four who developed acute myeloid leukemia, and all cases developed within 10 years following chemotherapy. All four patients with acute myeloid leukemia had been treated with prolonged therapy involving “complex multidrug historical regimens,” and had etoposide exposure. Other risks included oral cancers – primarily in those treated with MTX-FA plus other nonalkylating agents, and melanoma and meningioma, which were nonsignificantly increased in several treatment categories, they noted.

Patients treated with MTX-FA had a low risk of early menopause, but the risk was 13% by age 40, and 36% by age 45 years among those treated with EMA-CO, they said.

Dr Savage reported having no disclosures.

tor@frontlinemedcom.com

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