TY - JOUR
T1 - Combination gefitinib and methotrexate compared with methotrexate alone to treat ectopic pregnancy
AU - Skubisz, Monika M.
AU - Horne, Andrew W.
AU - Johns, Terrance G.
AU - Nilsson, Ulrika W.
AU - Duncan, W. Colin
AU - Wallace, Euan M.
AU - Critchley, Hilary O D
AU - Tong, Stephen
PY - 2013/10
Y1 - 2013/10
N2 - 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) n53; three doses (days 1-3) n53; seven doses (days 1-7) n56. 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]; P5.008). Median time for the ectopic pregnancies to resolve with combination therapy was 34% shorter compared with methotrexate alone (21 days compared with 32 days; P5.018). 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.
AB - 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) n53; three doses (days 1-3) n53; seven doses (days 1-7) n56. 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]; P5.008). Median time for the ectopic pregnancies to resolve with combination therapy was 34% shorter compared with methotrexate alone (21 days compared with 32 days; P5.018). 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.
UR - http://www.scopus.com/inward/record.url?scp=84887238944&partnerID=8YFLogxK
U2 - 10.1097/AOG.0b013e3182a14cfb
DO - 10.1097/AOG.0b013e3182a14cfb
M3 - Article
C2 - 24084530
AN - SCOPUS:84887238944
SN - 0029-7844
VL - 122
SP - 745
EP - 751
JO - Obstetrics and Gynecology
JF - Obstetrics and Gynecology
IS - 4
ER -