Pemetrexed is an anti-folate drug used for several cancers. It blocks the enzymes thymidylate synthase, dihydrofolate reductase and glycinamide ribonucleotide formyltransferase, which use folate to make the purine and thymidine building blocks of DNA.
Radiation recall is an inflammatory reaction in an area that was previously treated with radiation, triggered by a later drug. It looks like a severe sunburn, with redness, swelling and pain. It usually affects the skin but can also affect the lining of the mouth, the throat, the oesophagus, the small bowel, the lungs, muscles and brain. Many chemotherapy drugs can cause it, including doxorubicin, paclitaxel, docetaxel, etoposide, vinorelbine, vinblastine, gemcitabine and capecitabine, and two cases had been reported with pemetrexed.
Several factors affect the chance of radiation recall, such as the dose of radiation and the time between radiotherapy and chemotherapy. No minimum radiation dose has been identified; Azria and colleagues reported cases with doses from 10 to 81 Gy. The time gap matters for telling radiation recall apart from radiosensitisation, which happens within days (less than 7) of radiotherapy, whereas radiation recall can appear months or years after radiotherapy ends, and its symptoms are more severe.
Treatment includes corticosteroids (on the skin, by mouth or into a vein) or non-steroidal anti-inflammatory drugs, and stopping the drug that triggered it.
In February 2004, pemetrexed (with cisplatin) became the first drug approved by the FDA for malignant pleural mesothelioma that can't be removed by surgery, a rare cancer linked with asbestos exposure. In August 2004 it was approved on its own for advanced non-small cell lung cancer after earlier chemotherapy.
Between February 2004 and September 2007, the FDA received 12 reports of radiation recall after pemetrexed. The patients were aged 49 to 78 (average 62.5) and 9 of the 12 were men; 3 had mesothelioma, 7 non-small cell lung cancer and 2 an unspecified lung cancer. Radiation recall started on average 6 days (1 to 35 days) after pemetrexed was started, and the gap between radiotherapy and chemotherapy ranged from 15 days to 27 years. Some patients were treated with corticosteroids (7) or antibiotics (2). Outcomes were poor: five were admitted to hospital and one died of respiratory failure that may or may not have been due to radiation recall.
Doctors should be alert to the risk of radiation recall with pemetrexed, as some cases are very serious and may even need surgery.
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