Projects per year
Abstract / Description of output
Objective
To determine the safety, tolerability, and efficacy of combination gefitinib and methotrexate to treat ectopic pregnancy.
Methods
We performed a phase I, single-arm (nonrandomized), open-label study. Twelve women with ectopic pregnancies were administered methotrexate (50 mg/m2, intramuscular) and 250 mg oral gefitinib in a dose-escalation protocol: one dose (day 1) n=3; three doses (days 1–3) n=3; seven doses (days 1–7) n=6. Efficacy was examined by comparing human chorionic gonadotrophin (hCG) decline and time to resolution with historic controls administered methotrexate only.
Results
Common side effects were transient acneiform rash in 67% (8/12) and diarrhea in 42% (5/12) of participants. There was no clinical or biochemical evidence of serious pulmonary, renal, hepatic, or hematologic toxicity. Of six participants with a pretreatment serum hCG level between 1,000 and 3,000 international units/L, hCG levels declined significantly faster than in the control group. Median serum hCG levels by day 7 after treatment were less than one fifth of levels observed among 71 historic controls treated with methotrexate alone (median [interquartile range] hCG in participants 261 [55–1,445] international units/L compared with controls 1,426 [940–2,573]; P=.008). Median time for the ectopic pregnancies to resolve with combination therapy was 34% shorter compared with methotrexate alone (21 days compared with 32 days; P=.018).
Conclusion
Combination gefitinib and methotrexate has potential as a treatment for ectopic pregnancy but is commonly associated with minor side effects such as transient rash and diarrhea. The treatment requires validation of safety and efficacy in a larger trial.
Clinical Trial Registration
Australian New Zealand Clinical Trials Registry, www.anzctr.org, AC'TRN12610000684022.
LEVEL OF EVIDENCE: II
To determine the safety, tolerability, and efficacy of combination gefitinib and methotrexate to treat ectopic pregnancy.
Methods
We performed a phase I, single-arm (nonrandomized), open-label study. Twelve women with ectopic pregnancies were administered methotrexate (50 mg/m2, intramuscular) and 250 mg oral gefitinib in a dose-escalation protocol: one dose (day 1) n=3; three doses (days 1–3) n=3; seven doses (days 1–7) n=6. Efficacy was examined by comparing human chorionic gonadotrophin (hCG) decline and time to resolution with historic controls administered methotrexate only.
Results
Common side effects were transient acneiform rash in 67% (8/12) and diarrhea in 42% (5/12) of participants. There was no clinical or biochemical evidence of serious pulmonary, renal, hepatic, or hematologic toxicity. Of six participants with a pretreatment serum hCG level between 1,000 and 3,000 international units/L, hCG levels declined significantly faster than in the control group. Median serum hCG levels by day 7 after treatment were less than one fifth of levels observed among 71 historic controls treated with methotrexate alone (median [interquartile range] hCG in participants 261 [55–1,445] international units/L compared with controls 1,426 [940–2,573]; P=.008). Median time for the ectopic pregnancies to resolve with combination therapy was 34% shorter compared with methotrexate alone (21 days compared with 32 days; P=.018).
Conclusion
Combination gefitinib and methotrexate has potential as a treatment for ectopic pregnancy but is commonly associated with minor side effects such as transient rash and diarrhea. The treatment requires validation of safety and efficacy in a larger trial.
Clinical Trial Registration
Australian New Zealand Clinical Trials Registry, www.anzctr.org, AC'TRN12610000684022.
LEVEL OF EVIDENCE: II
Original language | English |
---|---|
Pages (from-to) | 745-751 |
Number of pages | 7 |
Journal | Obstetrics & Gynecology |
Volume | 122 |
Issue number | 4 |
DOIs | |
Publication status | Published - Oct 2013 |
Fingerprint
Dive into the research topics of 'Combination Gefitinib and Methotrexate Compared With Methotrexate Alone to Treat Ectopic Pregnancy'. Together they form a unique fingerprint.Projects
- 2 Finished
-
Polycystic ovary syndrome (PCOS): manipulation of hormonal metabolic and ovarian phenotypes using a developmental model
1/07/10 → 31/12/13
Project: Research
-
Improving women¿¿s health and pregnancy outcome: understanding the aetiology of ectopic pregnancy
1/02/10 → 31/01/14
Project: Research