Safety of topotecan monotherapy for relapsed small cell lung cancer patients with pre-existing interstitial lung disease

Cancer Chemother Pharmacol. 2015 Sep;76(3):499-505. doi: 10.1007/s00280-015-2816-6. Epub 2015 Jul 2.

Abstract

Purpose: To investigate the safety of intravenous topotecan monotherapy for relapsed small cell lung cancer (SCLC) patients with pre-existing interstitial lung disease (ILD).

Methods: A total of 77 patients who received topotecan for the treatment of relapsed SCLC between April 2007 and April 2014 were reviewed. Patients with pre-existing ILD were identified using the pretreatment chest computed tomography. The safety of intravenous topotecan for SCLC patients with ILD was retrospectively examined, particularly focusing on topotecan-induced acute exacerbation of ILD (AE-ILD).

Results: Twenty-three patients were identified as having pre-existing ILD [median age 74 (range 55-85) years; 21 men]. At the first topotecan administration, two-thirds (65.2%) had an Eastern Cooperative Oncology Group performance status 0 or 1. Topotecan was administered intravenously as second-line (n = 11) or later chemotherapy (n = 12). The median number of treatment cycles was two (range 1-7). The most common adverse events with grade 3 or 4 were neutropenia in 13 patients (56.5%) and thrombocytopenia in 10 patients (43.5%). Febrile neutropenia was observed in six patients (26.1%) and resulted in one death. AE-ILD occurred in five patients (21.7%; 95% confidence interval 4.9-38.5 %) 5-18 days after the last administration of topotecan and was fatal in three cases.

Conclusions: Intravenous topotecan monotherapy can be unsafe for relapsed SCLC patients with pre-existing ILD. Clinicians should be cautious regarding topotecan-induced AE-ILD as a lethal complication.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Female
  • Humans
  • Lung Diseases, Interstitial / drug therapy
  • Lung Diseases, Interstitial / physiopathology*
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / drug therapy*
  • Neoplasm Recurrence, Local / physiopathology
  • Retrospective Studies
  • Small Cell Lung Carcinoma / drug therapy*
  • Small Cell Lung Carcinoma / physiopathology
  • Topoisomerase I Inhibitors / adverse effects*
  • Topoisomerase I Inhibitors / therapeutic use*
  • Topotecan / adverse effects*
  • Topotecan / therapeutic use*

Substances

  • Topoisomerase I Inhibitors
  • Topotecan