Pemetrexed and interstitial lung disease

Our plain-English summary of Pemetrexed and interstitial lung disease, by B. Adhikari, R.M. Dongol, D. Baral, et al (Acta Oncologica, 2016).

The study

• Authors: B. Adhikari, R.M. Dongol, D. Baral, Y. Hewett, B.K. Shah
• Journal: Acta Oncologica
• Published: 2016;55(4):521-2
• Type of article: Letter
• Cited by: 6 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Summary of the article

This letter reported a study of the demographics and outcomes of interstitial lung disease (ILD) associated with pemetrexed, an antifolate chemotherapy drug approved in the USA in 2004 for malignant pleural mesothelioma and also used for metastatic non-small cell lung cancer. The authors retrospectively analysed pemetrexed-related adverse event reports made to the US FDA MedWatch database from February 2004 to February 2014. Cases were included if the patient had received at least one dose of pemetrexed and had ILD confirmed by radiograph or CT. The search returned 1915 adverse event reports, including 423 pulmonary events and 44 cases of ILD. Of these, 75% had non-small cell lung cancer and 22.7% had mesothelioma. The median age was 66 years and 68% were men. Fifty-nine percent were Asian, mainly Japanese, and 48% of all ILD patients were of Japanese origin. The median interval from starting treatment to ILD was 70 days. Most patients (36, 81.6%) received concomitant chemotherapy. Thirty-four percent were smokers, 23% had prior radiotherapy, 16% had asbestos exposure (six of the ten mesothelioma patients), 11% had COPD and 7% had pre-existing ILD. There were 20 deaths, a case fatality rate of 46%. Of the 15 patients with severe ILD at presentation, 12 died. The authors noted the limitations of voluntary reporting and concluded that ILD is an uncommon but serious adverse effect of pemetrexed.

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 reported a retrospective review of side-effect reports for pemetrexed sent to the US Food and Drug Administration's MedWatch database from February 2004 to February 2014. Pemetrexed is a chemotherapy drug used for malignant pleural mesothelioma and non-small cell lung cancer. The authors looked for cases of interstitial lung disease (ILD), a group of conditions affecting the tissue and space around the lungs' air sacs, confirmed by X-ray or CT scan. Of 1915 pemetrexed reports, 423 were lung events and 44 were ILD cases. Of these 44 patients, 75% had non-small cell lung cancer and 22.7% had mesothelioma. Their median age was 66, and 68% were men. Seven of the 44 (16%) had a history of asbestos exposure, including 6 of the 10 mesothelioma patients. There were 20 reported deaths, a case fatality rate of 46%. The authors concluded that ILD, although uncommon, is a serious side effect of pemetrexed. They noted that reporting is voluntary, so ILD may be undercounted. They also noted that records may be incomplete and that the sample was small.

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: Retrospective analysis of voluntary adverse-event reports in the FDA MedWatch database, published as a letter to the editor
• Who was studied: 44 patients with radiographically or CT-confirmed interstitial lung disease after at least one dose of pemetrexed, identified among 1915 pemetrexed adverse event reports (423 pulmonary events) made to the FDA MedWatch database, February 2004 to February 2014; 33 had non-small cell lung cancer and 10 had malignant mesothelioma; 59% were of Asian ethnicity, mainly Japanese, and 34% Caucasian
• Exposure: The chemotherapy drug pemetrexed (median of three doses, range 1 to 11, before the reported event), usually given with other chemotherapy. Asbestos exposure was recorded only as a patient history factor.
• Main results:
  • Among the 44 ILD cases, 75% had non-small cell lung cancer and 22.7% had mesothelioma; median age was 66 years and 68% were men
  • The median time from starting pemetrexed to ILD presentation was 70 days (range 1 to 403 days)
  • Among the 44 ILD patients, 34% were smokers, 23% had prior radiotherapy, 16% had a history of asbestos exposure, 11% had chronic obstructive pulmonary disease and 7% had pre-existing ILD
  • Asbestos exposure was recorded in 7 of 44 ILD patients overall (16%): 1 of 33 with non-small cell lung cancer (3%) and 6 of 10 with malignant mesothelioma (60%); it was not documented for 7 patients (16%)
  • Steroid plus supportive treatment was noted in 35 reports, with improvement or recovery in eight patients
  • There were 20 reported deaths among the 44 ILD cases, a case fatality rate of 46%
  • Of the 15 patients (34%) who had severe ILD when first seen, 12 died (80%)
• The authors' conclusion: The authors concluded that, although uncommon, ILD is a serious adverse effect of pemetrexed therapy, with a 46% case fatality rate. They suggested that increased awareness, prompt diagnosis and early intervention may reduce the risk of long-term lung damage or death.
• Limitations the authors state:
  • The study was retrospective, patient records may be incomplete, and confounding factors may be present
  • Because reporting of adverse events is voluntary, the study may underestimate how often ILD occurs in patients given pemetrexed
  • Differences in reported patient demographics and the small sample size hinder interpretation

Topics

Medical terms in this study, explained in our Lexicon: Pemetrexed (Alimta), Interstitial Lung Disease, Antifolate, Chemotherapy, Pleural Mesothelioma, Non-Small Cell Lung Cancer, Mesothelioma, Asbestos Exposure.

Related studies

• Incidence of interstitial lung disease in patients with mesothelioma in the west part of Japan — S. Nojiri, K. Gemba, et al. (2011)
• Possible value of antifibrotic drugs in patients with progressive fibrosing non-IPF interstitial lung diseases — S.E. Torrisi, N. Kahn, et al. (2019)
• The evidence of benefits of exercise training in interstitial lung disease: a randomised controlled trial — L.M. Dowman, C.F. McDonald, et al. (2017)
• Peribronchiolar metaplasia: a common histologic lesion in diffuse lung disease and a rare cause of interstitial lung disease: clinicopathologic features of 15 cases — J. Fukuoka, T.J. Franks, et al. (2005)
• Interstitial Lung Diseases in Developing Countries — P. Rivera-Ortega, M. Molina-Molina (2019)
• Diffuse intrapulmonary malignant mesothelioma masquerading as interstitial lung disease: a distinctive variant of mesothelioma — B.T. Larsen, J.R. Klein, et al. (2013)

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