Pemetrexed is increasingly used in combination with platinum antineoplastic agents for the treatment of certain lung malignancies. Its use was associated with favorable hematological adverse reaction compared to standard regimens. Non-hematological life-threatening complications such as gastrointestinal perforations are extremely rare with pemetrexed use and tend to develop in the distal bowel in patients at risk. We report the case of a 56-years old Arab male, heavy smoker newly diagnosed with Stage IV non-small cell lung cancer with no comorbidities, treated with pemetrexed-cisplatin combination. Four days after the first cycle of chemotherapy, the patient developed a small duodenal perforation that required emergency laparoscopy repair. Clinicians should have a high index of suspicion should be taken for alimentary tract perforation in patients presenting with acute abdominal pain during pemetrexed therapy.
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