Safety and efficacy of gemcitabine or pemetrexed in combination with a platinum in patients with non-small-cell lung cancer and prior interstitial lung disease

Cancer Chemother Pharmacol. 2014 Jun;73(6):1217-25. doi: 10.1007/s00280-014-2458-0. Epub 2014 Apr 3.

Abstract

Purpose: The incidence of lung cancer in patients with interstitial lung disease (ILD) is higher than in the general population; however, the clinical benefit of chemotherapy and the appropriate regimen for non-small-cell lung cancer (NSCLC) patients with ILD remain unclear. This study was conducted to elucidate the safety and efficacy of palliative chemotherapy with gemcitabine or pemetrexed, both in combination with a platinum agent in NSCLC patients with ILD.

Patients and methods: Patients with advanced or recurrent NSCLC and ILD who received gemcitabine or pemetrexed in combination with a platinum agent as first-line chemotherapy were retrospectively analyzed. Clinical outcomes, including response rate, overall survival (OS), and progression-free survival (PFS), in addition to the acute exacerbation of ILD after chemotherapy were investigated.

Results: Between January 2007 and December 2011, 52 patients were analyzed. The median age at chemotherapy was 67. Thirty-two patients (61.5 %) had adenocarcinoma histology. With respect to the types of ILD, idiopathic interstitial pneumonia (IIP) and non-IIP were observed in 42 (80.8 %) and 10 (19.2 %) patients, respectively. The FEV1 level was less than 80 % of the predicted value in 15 of the 41 patients in whom it was measured. The overall response rate was 42.3 % (95 % CI 28.8-55.9), and the median PFS was 5.4 months (95 % CI 4.6-6.2). The median OS was 7.9 months (95 % CI 5.5-10.3), and the 1-year survival rate was 31.7 % (95 % CI 19.0-44.4). Eight patients (15.4 %) died within 3 months of first-line chemotherapy. Multivariate analysis demonstrated that a heavy smoking history (40 or more pack-year smoking history) was an independent adverse prognostic factor for OS. An acute exacerbation of ILD (AE-ILD) caused by first-line chemotherapy was noted in 5.8 % of patients.

Conclusion: Our results suggest that gemcitabine or pemetrexed in combination with platinum agents could be a feasible option for advanced NSCLC with ILD with some risk of AE-ILD or early death. To establish the efficacy of palliative chemotherapy for patients with NSCLC and ILD, further well-controlled prospective studies are needed.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / adverse effects
  • Deoxycytidine / analogs & derivatives
  • Disease-Free Survival
  • Female
  • Gemcitabine
  • Glutamates / administration & dosage
  • Glutamates / adverse effects
  • Guanine / administration & dosage
  • Guanine / adverse effects
  • Guanine / analogs & derivatives
  • Humans
  • Lung Diseases, Interstitial / drug therapy
  • Lung Diseases, Interstitial / pathology
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Organoplatinum Compounds / administration & dosage
  • Organoplatinum Compounds / adverse effects
  • Pemetrexed
  • Retrospective Studies
  • Survival Rate

Substances

  • Glutamates
  • Organoplatinum Compounds
  • Pemetrexed
  • Deoxycytidine
  • Guanine
  • Gemcitabine