Fatal pemetrexed-induced lung injury in patients with advanced mesothelioma: a report of two cases

Our plain-English summary of Fatal pemetrexed-induced lung injury in patients with advanced mesothelioma: a report of two cases, by K. Nagata, R. Kaji, K. Tomii (Journal of Thoracic Oncology, 2010).

The study

• Authors: K. Nagata, R. Kaji, K. Tomii
• Journal: Journal of Thoracic Oncology
• Published: 2010;5(10):1714-5
• Type of article: Case report, Letter
• Cited by: 7 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Summary of the article

In this letter, the authors described two patients with advanced malignant pleural mesothelioma who developed fatal lung injury after receiving pemetrexed. They noted that only one earlier report of pemetrexed-induced lung injury had been published, and that case was mild and easily treated with corticosteroids. The patients were treated at Kobe City Medical Center General Hospital, Japan. The first, a 71-year-old man with sarcomatous mesothelioma, received cisplatin (60 mg/m2) and pemetrexed (500 mg/m2). He became breathless 4 weeks later. Chest CT showed diffuse ground-glass opacities in the right lung, and his KL-6 level was 2700 U/ml. The second, a 77-year-old man with biphasic mesothelioma, received carboplatin and pemetrexed (500 mg/m2). He developed progressive exertional breathlessness after 3 weeks, with ground-glass opacities in the left lower lobe and a KL-6 level of 1236 U/ml, which rose to 2417 U/ml before death. In both patients, extensive workup found no infectious, tumor-related, embolic or cardiac cause. Both received methylprednisolone 500 mg/d but worsened and died, 7 and 5 weeks after starting chemotherapy. Neither had taken any other new drug, and platinum agents rarely cause acute lung injury, so the authors concluded that pemetrexed was responsible. They noted that many risk factors reported for gefitinib-induced lung injury were present in both patients. They advised clinicians to be aware of this possible severe pulmonary complication.

PubMed has no abstract for this study, and the article doesn't print one. We wrote this summary from the full article with the help of AI. It is not the authors' wording.

In plain English

This letter to the editor described two men treated at a hospital in Kobe, Japan, for malignant pleural mesothelioma who developed fatal lung injury after chemotherapy including pemetrexed. The first, aged 71 with sarcomatous mesothelioma, received cisplatin and pemetrexed. Four weeks later he was short of breath, and a chest CT scan showed diffuse ground-glass opacities in the right lung. The second, aged 77 with biphasic-type mesothelioma, received carboplatin and pemetrexed. Three weeks later he had worsening breathlessness on exertion, with ground-glass opacities in the left lower lobe. In both men, blood levels of KL-6, which the authors noted is raised in interstitial lung diseases, were markedly increased. No infectious, tumor-related, embolic or cardiac cause was found. Despite high-dose methylprednisolone, they died 7 and 5 weeks after starting chemotherapy. Noting that platinum drugs rarely cause acute lung injury, the authors concluded that pemetrexed was responsible in both cases. The letter did not discuss asbestos. These are two case reports and do not show how often this occurs.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Letter to the editor reporting two cases
• Who was studied: Two men, aged 71 (sarcomatous malignant pleural mesothelioma) and 77 (biphasic-type malignant pleural mesothelioma), seen at Kobe City Medical Center General Hospital, Japan; dates not given
• Exposure: Chemotherapy with pemetrexed (500 mg/m2), combined with cisplatin (60 mg/m2) in the first patient and with carboplatin in the second; asbestos exposure was not discussed
• Main results:
  • First patient: 4 weeks after starting treatment he was short of breath, and chest CT showed diffuse ground-glass opacities in the right lung
  • First patient: white blood cell count 14,800/mm3, C-reactive protein 12.7 mg/dl, KL-6 2700 U/ml
  • First patient: despite methylprednisolone 500 mg/d he died 7 weeks after starting chemotherapy
  • Second patient: 3 weeks after starting treatment he had progressive exertional breathlessness, and chest CT showed ground-glass opacities in the left lower lobe
  • Second patient: white blood cell count 16,900/mm3, C-reactive protein 9.2 mg/dl, KL-6 1236 U/ml, rising to 2417 U/ml just before death
  • Second patient: despite methylprednisolone 500 mg/d he died 5 weeks after starting chemotherapy
  • In both patients no infectious, tumor-related, embolic or cardiac cause was found after extensive workup
  • Many of the risk factors reported elsewhere for lung injury from the drug gefitinib (smoking, male sex, coexisting interstitial pneumonia, early onset of disease, poor performance status) were present in both cases
• The authors' conclusion: The authors concluded that pemetrexed caused the lung injury in both cases, because platinum drugs rarely cause acute lung injury and no other new drug had been used. They said clinicians should be aware of this possible severe pulmonary complication with pemetrexed-containing regimens.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Pemetrexed (Alimta), Mesothelioma, Pleural Mesothelioma, Cisplatin, Biphasic Mesothelioma, Carboplatin, Chemotherapy.

Related studies

• Death receptor 5 and cellular FLICE-inhibitory protein regulate pemetrexed-induced apoptosis in human lung cancer cells — L. Su, G. Liu, et al. (2011)
• Pemetrexed-induced eyelid edema in lung cancer — P.R. Martins-Filho, S.Y. Kameo, et al. (2013)
• Retreatment with pemetrexed-based chemotherapy in patients with malignant pleural mesothelioma — G.L. Ceresoli, P.A. Zucali, et al. (2011)
• Molecular resistance fingerprint of pemetrexed and platinum in a long-term survivor of mesothelioma — O.D. Røe, A. Szulkin, et al. (2012)
• Enhanced apoptosis by pemetrexed and simvastatin in malignant mesothelioma and lung cancer cells by reactive oxygen species-dependent mitochondrial dysfunction and Bim induction — K.E. Hwang, Y.S. Kim, et al. (2014)
• Pharmacokinetic evaluation of pemetrexed — J.B. Sørensen (2011)

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