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 Trial

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

*Corresponding author for this work

Research output: Contribution to journalArticle

1 Citation (Scopus)
3 Downloads (Pure)

Abstract

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.

Original languageEnglish
Pages (from-to)276-281
Number of pages6
JournalEBioMedicine
Volume33
Early online date22 Jun 2018
DOIs
Publication statusPublished - Jul 2018

Fingerprint

Ectopic Pregnancy
Methotrexate
Labels
Surgery
Serum
Tubal Pregnancy
Epidermal Growth Factor Receptor
Therapeutics
Safety
Maternal Mortality
gefitinib
Exanthema
Diarrhea
Randomized Controlled Trials

Keywords

  • Ectopic pregnancy
  • Gefitinib
  • Medical treatment
  • Methotrexate
  • Phase II

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

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 Trial. / Skubisz, Monika M.; Tong, Stephen; Doust, Ann; Mollison, Jill; Johns, Terrance G.; Neil, Peter; Robinson, Miranda; Bhattacharya, Siladitya; Wallace, Euan; Krzys, Nicole; Colin Duncan, W.; Horne, Andrew W.

In: EBioMedicine, Vol. 33, 07.2018, p. 276-281.

Research output: Contribution to journalArticle

Skubisz, MM, Tong, S, Doust, A, Mollison, J, Johns, TG, Neil, P, Robinson, M, Bhattacharya, S, Wallace, E, Krzys, N, Colin Duncan, W & Horne, AW 2018, '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 Trial', EBioMedicine, vol. 33, pp. 276-281. https://doi.org/10.1016/j.ebiom.2018.06.017
Skubisz, Monika M. ; Tong, Stephen ; Doust, Ann ; Mollison, Jill ; Johns, Terrance G. ; Neil, Peter ; Robinson, Miranda ; Bhattacharya, Siladitya ; Wallace, Euan ; Krzys, Nicole ; Colin Duncan, W. ; Horne, Andrew W. / 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 Trial. In: EBioMedicine. 2018 ; Vol. 33. pp. 276-281.
@article{9ae71dd63a6747ca88934da701ba3065,
title = "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 Trial",
abstract = "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 = "Ectopic pregnancy, Gefitinib, Medical treatment, Methotrexate, Phase II",
author = "Skubisz, {Monika M.} and Stephen Tong and Ann Doust and Jill Mollison and Johns, {Terrance G.} and Peter Neil and Miranda Robinson and Siladitya Bhattacharya and Euan Wallace and Nicole Krzys and {Colin Duncan}, W. and Horne, {Andrew W.}",
note = "This work was supported by an NHMRC Grant (#1008276) to ST, TJ and EW, and an MRC Centenary Award (G0802808) to AH. The funders had no role study design, collection, analysis, and interpretation of data; in the writing of the report or in the decision to submit the paper.",
year = "2018",
month = "7",
doi = "10.1016/j.ebiom.2018.06.017",
language = "English",
volume = "33",
pages = "276--281",
journal = "EBioMedicine",

}

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.

N1 - This work was supported by an NHMRC Grant (#1008276) to ST, TJ and EW, and an MRC Centenary Award (G0802808) to AH. The funders had no role study design, collection, analysis, and interpretation of data; in the writing of the report or in the decision to submit the paper.

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

VL - 33

SP - 276

EP - 281

JO - EBioMedicine

JF - EBioMedicine

ER -