Pemetrexed for advanced non-small cell lung cancer patients with interstitial lung disease

BMC Cancer. 2014 Jul 10;14:508. doi: 10.1186/1471-2407-14-508.


Background: Non-small cell lung cancer (NSCLC) patients with interstitial lung disease (ILD) need to be approached carefully given the high incidence of pulmonary toxicity. Pemetrexed (PEM) is the key drug for the treatment of NSCLC. However, its safety, especially with respect to the exacerbation of ILD, and efficacy in NSCLC patients with ILD have yet to be established.

Method: We investigated the safety and efficacy of PEM monotherapy in NSCLC patients with or without idiopathic interstitial pneumonia (IIPs). The medical charts of these patients were retrospectively reviewed.

Results: Twenty-five patients diagnosed as having IIPs (IIPs group) and 88 patients without ILD (non-ILD group) were treated with PEM monotherapy at Juntendo University Hospital between 2009 and 2013. In the IIPs group, 12 patients were found to have usual interstitial pneumonitis (UIP) on chest computed tomography (CT) (UIP group) and the other 13 patients showed a non-UIP pattern on chest CT (non-UIP IIPs group). Three patients in the IIPs group (2 in the UIP group and 1 in the non-UIP IIPs group) and 1 in the non-ILD group developed pulmonary toxicity during treatment (3.5% overall, 12.0% in the IIPs group versus 1.1% in the non-ILD group). Moreover, all 3 patients in the IIPs group died of pulmonary toxicity. Overall survival tended to be longer in the non-ILD group than in the IIPs group (p = 0.08). Multivariate analyses demonstrated that IIPs was the only significant independent risk factor for PEM-related pulmonary toxicity.

Conclusion: We found that the incidence of PEM-related pulmonary toxicity was significantly higher amongst NSCLC patients with IIPs than among those without IIPs. Particular care must be taken when administering PEM to treat NSCLC patients with IIPs.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / toxicity*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Female
  • Glutamates / administration & dosage
  • Glutamates / toxicity*
  • Guanine / administration & dosage
  • Guanine / analogs & derivatives*
  • Guanine / toxicity
  • Humans
  • Idiopathic Interstitial Pneumonias / complications*
  • Idiopathic Interstitial Pneumonias / mortality*
  • Lung Neoplasms / drug therapy*
  • Male
  • Middle Aged
  • Pemetrexed
  • Survival Analysis


  • Antineoplastic Agents
  • Glutamates
  • Pemetrexed
  • Guanine