Non-tubal
ectopic pregnancies are a rare subgroup of
ectopic pregnancies implanted at sites other than the Fallopian tube. Mortality from non-tubal
ectopic pregnancies is higher compared with that for tubal
ectopic pregnancies, and they are becoming more 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 effective medical
therapies to resolve non-tubal
ectopic pregnancies and reduce operative intervention. We have recently reported successful use of combination
gefitinib (an orally available
epidermal growth factor receptor inhibitor) and
methotrexate for treatment of
tubal pregnancies. To our knowledge, this combination has not been used to treat non-
tubal pregnancies. Here we report the use of combination
gefitinib and
methotrexate 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/m² on Day 1, ± Day 4 or Day 7) with seven once daily doses of oral
gefitinib (250 mg). The women were monitored 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 outcomes were also recorded. All eight women were 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 resumed menstruation and importantly, three women subsequently conceived spontaneously. Two have 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.