Changes in the diffusion capacity for carbon monoxide and the development of non-infectious pneumonitis in patients with metastatic renal cell carcinoma treated with everolimus

Anticancer Res. 2014 Oct;34(10):5723-8.

Abstract

Aim: The aim of the present study was to evaluate how treatment with everolimus changes readouts of the pulmonary function test (PFT) in patients with metastatic renal cell carcinoma (mRCC). We also attempted to determine whether changes of PFT or everolimus-associated non-infectious pneumonitis (NIP) might affect the efficacy of everolimus.

Materials and methods: The results of PFTs, radiological reports and medical records of 36 mRCC patients treated with everolimus after failure to vascular endothelial growth factor receptor-tyrosine kinase inhibitor (VEGFR-TKI) were reviewed.

Results: Whereas 9 patients (30%) developed radiological changes consistent with everolimus-associated NIP (pneumonitis group), 27 were included in the non-pneumonitis group. The baseline value of the diffusing capacity for carbon monoxide divided by the alveolar volume (DLco/VA) was 90%. It decreased significantly as the duration of treatment increased (p<0.01). There was no significant difference in DLco/VA values between patients with and without NIP either at baseline (p=0.28) and 6 weeks after the initiation of everolimus therapy (p=0.18). The changes in DLco/VA between baseline and 6 weeks did not differ between the two groups (p=0.55). Time-dependent covariate Cox analysis, indicated that the decrease in DLco/VA was not correlated with the efficacy of everolimus in terms of progression-free survival (PFS; HR=1.0, p=0.94) and overall survival (OS; HR=0.98, p=0.18), whereas development of NIP was associated with worse PFS (HR=4.60, p=0.01).

Conclusion: Patients with mRCC who are receiving everolimus therapy display a reduction in DLco/VA over time. However, neither the baseline DLco/VA nor the change in DLco/VA over time can help predict either development of NIP or the efficacy of everolimus.

Keywords: Metastatic renal cell carcinoma; everolimus; pneumonitis; pulmonary function test.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / adverse effects*
  • Antineoplastic Agents / therapeutic use
  • Carbon Monoxide / metabolism*
  • Carcinoma, Renal Cell / complications*
  • Carcinoma, Renal Cell / drug therapy
  • Carcinoma, Renal Cell / pathology
  • Everolimus
  • Female
  • Humans
  • Kidney Neoplasms / complications*
  • Kidney Neoplasms / drug therapy
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Pneumonia / chemically induced*
  • Pneumonia / physiopathology*
  • Pulmonary Diffusing Capacity / drug effects*
  • Respiratory Function Tests
  • Sirolimus / adverse effects
  • Sirolimus / analogs & derivatives*
  • Sirolimus / therapeutic use
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Carbon Monoxide
  • Everolimus
  • Sirolimus