CASE REPORT Early pregnancy Combination gefitinib and methotrexate treatment for non-tubal ectopic pregnancies: a case series

Non-tubal ectopic pregnancies are a rare subgroup of ectopic pregnancies implanted at sites other than the Fallopian tube. Mortality fromnon-tubal ectopic pregnancies is higher comparedwith that for tubal ectopic pregnancies, and theyarebecomingmore common, partly due to the rising incidence of Caesarean sections and use of assisted reproductive technologies. Non-tubal ectopic pregnancies can be especially difficult to treat. Surgical treatment is complex, and follow-up after medical treatment is usually protracted. There is therefore a need for more effectivemedical therapies to resolvenon-tubal ectopic pregnancies and reduceoperative intervention.Wehave recently reported successful use of combination gefitinib (an orally available epidermal growth factor receptor inhibitor) andmethotrexate for treatment of tubal pregnancies. To our knowledge, this combination has not been used to treat non-tubal pregnancies. Herewe report the use of combination gefitinib andmethotrexate to treat eight women with stable, non-tubal ectopic pregnancies at two tertiary academic teaching hospitals (Edinburgh, UK and Melbourne, Australia); five interstitial and three Caesarean section scar ectopic pregnancies. Pretreatment serum hCG levels ranged from 2458 to 48 550 IU/l, and six women had pretreatment hCG levels .5000 IU/l. The women were co-administered 1–2 doses of i.m. methotrexate (50 mg/m onDay 1,+ Day 4 or Day 7) with seven once daily doses of oral gefitinib (250 mg). Thewomenweremonitored until complete resolution of the ectopic pregnancy, defined as a serum hCG,15 IU/l. Time to resolution (days from first methotrexate dose until serum hCG,15 IU/l), safety and tolerability, complication rates and subsequent fertility outcomeswere also recorded.All eightwomenwere successfully treated with combination gefitinib and methotrexate. The most common side effects were transient acne/rash and diarrhoea, known side effects of gefitinib. All women promptly resumedmenstruation and importantly, threewomen subsequently conceived spontaneously. Twohave delivered a healthy infant at term and the third is currently in her second trimester of pregnancy. Hence, our case series supports a future clinical trial to determine the efficacy of combination gefitinib and methotrexate to treat non-tubal ectopic pregnancies.