Methotrexate Toxicity & Dactinomycin Resistance During Treatment for Benign Gestational Trophoblastic Disease: Case Report and Management with Combination Therapy

Background: Gestational trophoblastic disease GTD is a rare group of malignant and benign tumors that results from the abnormal proliferation of placental tissue after conception in women. In the United States, GTD occurs in 1 in 1000 pregnancies. Case: A 35-year-old female presented to the emergency room due to concerns about a rise in bHCG levels three times. The patient was pregnant, and an evacuation due to suspicion of a bladder mole was performed at 8 weeks and 5 days of pregnancy. There was cramp-like pain in the lower abdomen and dizziness. Tatts-hCG showed an increase from 279,000 to 426,000 IU/L. Ultrasound before the evacuation confirmed a morphologically spotted hydatidiform mole. Intervention: The patient was initiated on a four-day regimen of low-dose methotrexate administered every 2 weeks, as per National Comprehensive Cancer Network guidelines. It is the first case ever reported in Norway in which the patient's voice was affected due to methotrexate hypersensitivity. Due to persistent reaction to methotrexate patient was switched to a 4-day regimen of dactinomycin. Due to dactinomycin resistance, the patient was switched to combination therapy, which includes EMA-CO etoposide, dactinomycin, cyclophosphamide, and vincristine without methotrexate. Outcome: Patient completely recovered from benign gestational trophoblastic disease and her bHCG levels normalized (<0.2 IU/L) within five months.Conclusion: This study concluded that proper monitoring of bHCG levels and early detection of methotrexate toxicity and dactinomycin resistance are important to achieve complete recovery in GTD with reduced risk of morbidity. This study also determined that EMA-CO is the best choice of combination therapy regimen in case of methotrexate toxicity/dactinomycin resistance, low-risk GTD, and high-risk GTD.