A patient with malignant pleural mesothelioma complicated with Dubin–Johnson syndrome treated with cisplatin/pemetrexed combination therapy: the need to consider mutation to the ATP-binding cassette-C2 gene and the pharmacokinetics of pemetrexed

Abstract

Dubin–Johnson syndrome is a form of constitutional jaundice induced by a mutated ATP-binding cassette-C2 (ABCC2) gene. The ABCC2 gene is involved in the excretion of drugs. We recently treated a patient with malignant pleural mesothelioma complicated with Dubin–Johnson syndrome with cisplatin/pemetrexed combination therapy. One-third of the dose compared to the standard dose of pemetrexed was administered during the first course. We increased the dose of pemetrexed in stages after evaluating the patient for adverse effects. Cisplatin was combined beginning in the fourth course. The adverse effects of cisplatin/pemetrexed combination therapy were slight, and the patient exhibited a partial response. We measured the blood concentration and analyzed the pharmacokinetics of pemetrexed. As a result, the excretion of pemetrexed was found to be good, and no delay of excretion was observed compared to that in normal patients. It was previously reported that the ABCC2 gene is expressed in the kidneys. However, it appears that ABCC2 might not be related to the excretion of pemetrexed. These results suggest that standard dose cisplatin/pemetrexed combination therapy could be conducted for patient with malignant pleural mesothelioma complicated with Dubin–Johnson syndrome from the first course.