Unusal lung damage associated with pemetrexed in malignant pleural mesothelioma: A case report

Summary A 64-year-old male was diagnosed with malignant pleural mesothelioma (MPM) in June 2006 after complaining of dyspnoea and a persistent cough. In July 2006 the patient underwent talc pleurodesis and started first-line chemotherapy with cisplatin associated with pemetrexed (Alimta ® ). At the end of the third chemotherapy cycle the disease was stable and no significant drug toxicity was recorded. The patient progressed through another three cycles under the same treatment schedule. Restaging at the end of the sixth cycle confirmed a stable disease and the patient started follow-up. In January 2007, further restaging showed disease progression and the patient was enrolled in a phase I clinical trial involving a continuous infusion of pemetrexed until at a dose of 100 mg m −2 at day one. After 8 days the patient was referred to the Accident and Emergency Department for acute dyspnoea and a fever of 38.5 °C. A high resolution CT-scan of the thorax showed diffuse, bilateral areas of ground glass attenuation with a patchy distribution. A 13-day broad-spectrum antibiotic therapy did not achieve any clinical and/or radiological improvement of respiratory abnormalities, and for this reason a bronchoscopy, with a fluoroscopic-guided transbronchial lung biopsy (TBB), and a bronchoalveolar lavage (BAL), were performed. BAL cultures for common bacteria, acid fast bacilli and fungi, as well as vial cultures and/or immunofluorescent tests for viruses (cytomegalovirus, adenovirus, herpes simplex virus, syncytial respiratory virus, influenzae and parainfluenzae viruses) and Legionellae, proved negative. Examination of BAL cytospin preparations, stained by both Diff-Quick and Papanicolaou methods, showed cuboidal hyperplastic/dysplastic cells (diffuse alveolar damage cells) whilst no malignant cells, viral inclusions, fungi, or Pneumocystis jiroveci cysts were identified. The TBB showed remnants of jaline membranes in the alveolar spaces along with granulation tissue partly obliterating the alveolar spaces, and slight thickening of the interalveolar septa. Plump elongated reactive type II pneumocytes covering the alveolar septa were also numerous. A regimen of 200 mg methylprednisolone once a day was started and a partial remission of clinical and radiological abnormalities was achieved. Based on our clinical and radiological findings we therefore conclude a possible diagnosis of drug-induced toxicity by pemetrexed chemotherapy in continuous infusion.