Lung Cancer Drug May Be Alternative to Surgery for Ectopic Pregnancy

Women with ectopic pregnancies that may be too advanced for treatment with methotrexate (MTX) alone may one day have an alternative medical treatment with the addition of the lung cancer drug gefitinib, according to researchers who conducted a small clinical trial in Edinburgh, UK.

Typically, tubal ectopic pregnancies with pretreatment serum human chorionic gonadotropin (hCG) levels of less than 1000 IU/L respond well to outpatient medical treatment with intramuscular MTX. However, tubal ectopic pregnancies with pretreatment serum hCG levels of greater than 1000 IU/L take a significant time to resolve with MTX alone and generally require multiple outpatient visits for monitoring.

Gefitinib, an orally active epidermal growth factor receptor antagonist, used in combination with the conventional treatment of MTX was more effective at resolving an ectopic pregnancy than MTX alone, the study found. Gefitinib works by blocking a protein that is known to encourage cell growth. In preclinical studies, the researchers found that high levels of epidermal growth factor receptor were present at the implantation site of ectopic pregnancies. They also discovered that gefitinib augments MTX-induced regression of pregnancy-like tissues.

In a toxicity study, oral gefitinib and intramuscular MTX were administered to 12 women with tubal ectopic pregnancies. Treatment involved a single dose of MTX, 50 mg/m², administered intramuscularly, and a dose escalation protocol of oral gefitinib, 250 mg/d. Three women received 1 dose of gefitinib (day 1), 3 women received 3 doses (days 1-3), and 6 women received 7 doses (days 1-7).

Of 6 patients with a pretreatment serum hCG level between 1000 and 3000 IU/L, hCG levels declined significantly faster than those in the control group. By day 7 post-treatment, median serum hCG levels were less than one fifth of those of 71 historic controls treated with MTX alone (261 IU/L vs 1426 IU/L, respectively). Ectopic pregnancies treated with combination treatment resolved 34% faster than those treated with MTX alone (21 days vs 32 days; P=0.018).

Transient acneiform rash and diarrhea were the most common adverse effects. Eight (67%) of 12 women experienced rash, and 5 (42%) of 12 women experienced diarrhea. There was no clinical or biochemical evidence of serious pulmonary, renal, hepatic, or hematological toxicity, reported the study authors.

If this treatment progresses through clinical trials, there is potential to preserve the patient’s level of fertility by reducing the need for surgical removal of the fallopian tube. The validation of these results in a larger study is needed before this treatment can be recommended for approval.

Pertinent Points:
- The lung cancer drug gefitinib, in combination with methotrexate, may be a promising therapy for tubal ectopic pregnancy.
- Methotrexate plus gefitnib, compared with methotrexate alone, was more effective and associated with a shorter time to successful treatment of tubal ectopic pregnancy in women who did not require surgery.

References:

Skubisz MM, Horne AW, Johns TG, et al. Combination gefitinib and methotrexate compared with methotrexate alone to treat ectopic pregnancy. Obstet Gynecol. 11 September 2013. doi: 10.1097/AOG.0b013e3182a14cfb