On February 4, 2004, the FDA approved pemetrexed for injection (Alimta®, made by Eli Lilly and Company) in combination with cisplatin for the treatment of patients with malignant pleural mesothelioma whose disease is either unresectable or who are not otherwise candidates for curative surgery.

Safety and efficacy were demonstrated in one multicenter, randomized trial in 456 patients comparing the combination of Alimta and cisplatin with cisplatin alone. Supplementation with vitamin B12 and folic acid was instituted during the trial to decrease adverse effects. Subsequently, all patients, including previously enrolled patients, were given vitamin supplementation.

In an analysis of all patients who were randomized and treated, the combination of Alimta and cisplatin was associated with a statistically significant improvement in survival compared to cisplatin alone. The median survivals were 12.1 versus 9.3 months, respectively (p = 0.020). This superiority in the combination arm was also demonstrated in the fully vitamin supplemented subgroup. The median survivals were 13.3 and 10.0 months in the combination and cisplatin alone groups, respectively (p = 0.051).

The principal adverse effects of the Alimta plus cisplatin regimen were myelosuppression (in which the bone marrow produces fewer blood cells), fatigue, nausea, vomiting, and dyspnea (difficulty breathing). Most grade 3-4 adverse effects were significantly reduced by vitamin supplementation without any efficacy decrement.

Alimta, 500 mg/m2, was diluted in 100 mL normal saline and administered as a 10-minute intravenous infusion. Approximately 30 minutes after Alimta administration, cisplatin, 75 mg/m2 over 2 hours, was administered. Both drugs were given every 21 days.

Folic acid, 350 to 1000 micrograms orally, was given daily, beginning 1 to 3 weeks prior to the first chemotherapy dose and continued daily for one to three weeks after treatment discontinuation. A vitamin B12 injection, 1000 micrograms intramuscularly, was administered one to three weeks before the first chemotherapy dose and repeated approximately every nine weeks until treatment discontinuation.

Dexamethasone 4 mg (or an equivalent corticosteroid) twice daily was administered orally for skin rash prophylaxis to all patients one day prior to, on the day of, and one day after each Alimta dose.

Full prescribing information is available, including clinical trial information, safety, dosing, drug-drug interactions and contraindications.

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