Drug-related pneumonitis in patients with advanced renal cell carcinoma treated with temsirolimus

Jose Pablo Maroto, Gary Hudes, Janice P. Dutcher, Theodore F. Logan, Charles S. White, Mizue Krygowski, Maria Cincotta, Mark Shapiro, Ignacio Duran, Anna Berkenblit

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89 Scopus citations

Abstract

Purpose: Pneumonitis has occurred in patients treated with inhibitors of the mammalian target of rapamycin (mTOR). In a phase III study of patients with previously untreated, poor-prognosis, advanced renal cell carcinoma (ARCC), the mTOR inhibitor temsirolimus improved survival compared with interferon. We performed a retrospective, independent, blinded radiographic review of chest computed tomography (CT) images of patients in this study to characterize temsirolimusrelated pneumonitis. Patients and Methods: Patients were treated with intravenous temsirolimus 25 mg once weekly or subcutaneous interferon alfa 3 million units, with an increase to 18 million units, thrice weekly. Drug-related pneumonitis was identified based on sequential chest CT images, required every 8 weeks, showing changes consistent with pneumonitis and not pneumonia (infection) or disease progression as correlated with clinical data. Cumulative probability of drug-related pneumonitis was estimated using the Kaplan-Meier method. Results: Eight (6%) of 138 and 52 (29%) of 178 evaluable patients on interferon and temsirolimus treatment, respectively, developed radiographically identified drug-related pneumonitis. Time to onset of pneumonitis was significantly shorter on the temsirolimus arm than on the interferon arm (log-rank P < .001). Estimated cumulative probability of pneumonitis at 8 and 16 weeks from first dose was 21% and 31%, respectively, on the temsirolimus arm and 6% and 8%, respectively, on the interferon arm. Respiratory symptoms were observed around time of onset of radiographically diagnosed temsirolimus-related pneumonitis in 16 (31%) of 52 patients. Conclusion: Patients with ARCC receiving temsirolimus should be monitored closely for development of pneumonitis, and their management should be altered if clinical symptoms appear.

Original languageEnglish (US)
Pages (from-to)1750-1756
Number of pages7
JournalJournal of Clinical Oncology
Volume29
Issue number13
DOIs
StatePublished - May 1 2011

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Maroto, J. P., Hudes, G., Dutcher, J. P., Logan, T. F., White, C. S., Krygowski, M., Cincotta, M., Shapiro, M., Duran, I., & Berkenblit, A. (2011). Drug-related pneumonitis in patients with advanced renal cell carcinoma treated with temsirolimus. Journal of Clinical Oncology, 29(13), 1750-1756. https://doi.org/10.1200/JCO.2010.29.2235