TY - JOUR
T1 - Gefitinib and Methotrexate to Treat Ectopic Pregnancies with a Pre-Treatment Serum hCG 1000–10,000 IU/L
T2 - Phase II Open Label, Single Arm Multi-Centre Trial
AU - Skubisz, Monika M.
AU - Tong, Stephen
AU - Doust, Ann
AU - Mollison, Jill
AU - Johns, Terrance G.
AU - Neil, Peter
AU - Robinson, Miranda
AU - Bhattacharya, Siladitya
AU - Wallace, Euan
AU - Krzys, Nicole
AU - Colin Duncan, W.
AU - Horne, Andrew W.
PY - 2018/7
Y1 - 2018/7
N2 - Background: Ectopic pregnancies are a leading cause of maternal mortality. Most are treated surgically. We evaluated the efficacy and safety of combining oral gefitinib (epidermal growth factor receptor inhibitor) with methotrexate to treat larger ectopic pregnancies. Methods: We performed a phase II, single arm, open label study across four hospitals in Edinburgh and Melbourne. We recruited women with a stable tubal ectopic pregnancy and a pre-treatment serum hCG between 1000 and 10,000 IU/L. We administered intramuscular methotrexate (50 mg/m2) once, and oral gefitinib (250 mg) for seven days. The primary outcome was the percentage successfully treated without needing surgery. To show the treatment is at least 70% effective, 28 participants were required, and 24 or more successfully treated without surgery. Secondary outcomes were safety, tolerability, and time to resolution. This study is registered (ACTRN12611001056987). Findings: 30 participants with stable tubal ectopic pregnancies were recruited but two withdrew, leaving 28 participants. The median (± range) pre-treatment serum hCG was 2039 (1031–8575) IU/L and nine had pre-treatment hCGs levels >3000 IU/L. The treatment successfully resolved 86% (24/28) cases with a median (±range) time to resolution of 32 (18–67) days. The treatment caused transient rash and diarrhoea, but no serious adverse events. Interpretation: Combination gefitinib and methotrexate is at least 70% effective in resolving ectopic pregnancies with a pre-treatment serum hCG 1000–10,000 IU/L. This may be a new way to treat most stable ectopic pregnancies, but needs to be validated via a randomised clinical trial.
AB - Background: Ectopic pregnancies are a leading cause of maternal mortality. Most are treated surgically. We evaluated the efficacy and safety of combining oral gefitinib (epidermal growth factor receptor inhibitor) with methotrexate to treat larger ectopic pregnancies. Methods: We performed a phase II, single arm, open label study across four hospitals in Edinburgh and Melbourne. We recruited women with a stable tubal ectopic pregnancy and a pre-treatment serum hCG between 1000 and 10,000 IU/L. We administered intramuscular methotrexate (50 mg/m2) once, and oral gefitinib (250 mg) for seven days. The primary outcome was the percentage successfully treated without needing surgery. To show the treatment is at least 70% effective, 28 participants were required, and 24 or more successfully treated without surgery. Secondary outcomes were safety, tolerability, and time to resolution. This study is registered (ACTRN12611001056987). Findings: 30 participants with stable tubal ectopic pregnancies were recruited but two withdrew, leaving 28 participants. The median (± range) pre-treatment serum hCG was 2039 (1031–8575) IU/L and nine had pre-treatment hCGs levels >3000 IU/L. The treatment successfully resolved 86% (24/28) cases with a median (±range) time to resolution of 32 (18–67) days. The treatment caused transient rash and diarrhoea, but no serious adverse events. Interpretation: Combination gefitinib and methotrexate is at least 70% effective in resolving ectopic pregnancies with a pre-treatment serum hCG 1000–10,000 IU/L. This may be a new way to treat most stable ectopic pregnancies, but needs to be validated via a randomised clinical trial.
KW - Ectopic pregnancy
KW - Gefitinib
KW - Medical treatment
KW - Methotrexate
KW - Phase II
UR - http://www.scopus.com/inward/record.url?scp=85048938616&partnerID=8YFLogxK
U2 - 10.1016/j.ebiom.2018.06.017
DO - 10.1016/j.ebiom.2018.06.017
M3 - Article
C2 - 29941341
AN - SCOPUS:85048938616
SN - 2352-3964
VL - 33
SP - 276
EP - 281
JO - EBioMedicine
JF - EBioMedicine
ER -