Alimta Reportedly Caused Lung Injury

A Japanese medical journal recently reported a case of pemetrexed-induced acute lung injury in a patient with mesothelioma. In the U.S., Alimta is the brand name for pemetrexed.

According to this report a 65-year-old man was admitted to the hospital after complaining of shortness of breath. Doctors ordered a chest x-ray which showed that the patient had excess fluid that had accumulated in the left pleural cavity, the fluid-filled space that surrounds the lungs. A chest CT scan was ordered which revealed multiple pleural masses on the left side. A needle biopsy removed a specimen from one of the masses and pathology tests were performed on the sample. The diagnosis of malignant pleural mesothelioma was subsequently made.

The patient was started on the combination chemotherapy of pemetrexed and carboplatin. The day after starting chemotherapy, the patient had fever and shortness of breath. Chest CT scan showed diffuse lung opacity mainly in the right lung. This was suggestive of drug-induced interstitial pneumonia. Corticosteroid pulse therapy was started, but the patient died of respiratory failure ten days after beginning chemotherapy. The researchers concluded that “this is apparently the first reported case of pemetrexed-induced acute lung injury.”

Pemetrexed, brand name Alimta is an antifolate antineoplastic agent. It is FDA approved for the treatment of mesothelioma in combination with another chemo drug called cisplatin and this combination is standard first-line chemotherapy for unresectable malignant mesothelioma. Pemetrexed disrupts folate-dependent metabolic processes essential for cell replication. The drug insert that accompanies pemetrexed discusses the clinical trials that led to the drug’s approval. This information includes:

One patient with severe renal impairment (creatinine clearance 19 mL/min) who did not receive folic acid and vitamin B12 died of drug-related toxicity following administration of ALIMTA alone…ALIMTA can suppress bone marrow function, manifested by neutropenia, thrombocytopenia, and anemia…ALIMTA may cause fetal harm when administered to a pregnant woman…Pemetrexed was fetotoxic and teratogenic in mice. No carcinogenicity studies have been conducted with pemetrexed.”

The insert also lists adverse events (side effects) from the drugs:

Adverse Events Out of 168 Patients:

Event Number Neutropenia 58 Leukopenia 55 Anemia 33 Thrombocytopenia 27 Creatinine elevation 16 Renal failure 2 Fatigue 80 Fever 17 Other constitutional symptoms 11 Thrombosis/embolism 7 Nausea 84 Vomiting 58 Constipation 44 Anorexia 35 Stomatitis/pharyngitis 28 Diarrhea without colostomy 26 Dehydration 7 Dysphagia/esophagitis/odynophagia 6 Dyspnea 66 Chest pain 40 Neuropathy/sensory 17 Mood alteration/depression 14 Infection without neutropenia 11 Infection with grades 3 or 4 neutropenia 6 Infection/febrile neutropenia-other 3 Febrile neutropenia 1 Allergic reaction/hypersensitivity 2 Rash/desquamation 22

These side effects were less in patients who were supplemented with daily folic acid and vitamin B12. In the clinical trial that led to its FDA approval, pemetrexed plus cisplatin resulted in a median survival of 12.1 months in randomized and treated patients versus 9.3 months in patients who only recived cisplatin. For fully supplemented patients, individuals who received pemetrexed plus cisplatin had a median survival of 13.3 months versus 10.0 months for patients who only received cisplatin. There was no comparison made to patients who did not receive any chemo of any kind.

Sources: FDA Website and Sakamoto S, et al., Case of pemetrexed-induced acute lung injury [Article in Japanese] Nihon Kokyuki Gakkai Zasshi. 2009 May;47(5):415-20.