Gefitinib and Methotrexate to Treat Ectopic Pregnancies with a Pre-Treatment Serum hCG 1000–10,000 IU/L: Phase II Open Label, Single Arm Multi-Centre TrialResearch in context
Monika M. Skubisz,
Stephen Tong,
Ann Doust,
Jill Mollison,
Terrance G. Johns,
Peter Neil,
Miranda Robinson,
Siladitya Bhattacharya,
Euan Wallace,
Nicole Krzys,
W. Colin Duncan,
Andrew W. Horne
Affiliations
Monika M. Skubisz
Translational Obstetrics Group, Department of Obstetrics and Gynaecology, University of Melbourne, Heidelberg 3084, Victoria, Australia; Mercy Perinatal, Mercy Hospital for Women, Heidelberg 3084, Victoria, Australia; The Hudson Institute, Clayton 3168, Australia; Monash Health, Clayton 3168, Victoria, Australia
Stephen Tong
Translational Obstetrics Group, Department of Obstetrics and Gynaecology, University of Melbourne, Heidelberg 3084, Victoria, Australia; Mercy Perinatal, Mercy Hospital for Women, Heidelberg 3084, Victoria, Australia; Corresponding author at: Department of Obstetrics and Gynaecology, University of Melbourne, Level 4 Mercy Hospital for Women, 163 Studley Rd., Heidelberg 3084, Victoria, Australia.
Ann Doust
MRC Centre for Reproductive Health, University of Edinburgh, Edinburgh EH16 4TJ, United Kingdom
Jill Mollison
University of Oxford, Nuffield Department of Primary Health Sciences, Oxford OX2 6GG, United Kingdom
Terrance G. Johns
The Hudson Institute, Clayton 3168, Australia
Peter Neil
Monash Health, Clayton 3168, Victoria, Australia
Miranda Robinson
Mercy Perinatal, Mercy Hospital for Women, Heidelberg 3084, Victoria, Australia
Siladitya Bhattacharya
Institute of Applied Health Sciences, University of Aberdeen, Aberdeen AB25 2ZD, United Kingdom
Euan Wallace
The Hudson Institute, Clayton 3168, Australia; Monash Health, Clayton 3168, Victoria, Australia
Nicole Krzys
Mercy Perinatal, Mercy Hospital for Women, Heidelberg 3084, Victoria, Australia
W. Colin Duncan
MRC Centre for Reproductive Health, University of Edinburgh, Edinburgh EH16 4TJ, United Kingdom
Andrew W. Horne
MRC Centre for Reproductive Health, University of Edinburgh, Edinburgh EH16 4TJ, United Kingdom
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. Keywords: Gefitinib, Methotrexate, Ectopic pregnancy, Medical treatment, Phase II
