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

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 temsirolimus-related 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.

• Authors: Jose Pablo Maroto, Gary Hudes, Janice P Dutcher, Theodore F Logan, Charles S White, Mizue Krygowski, Maria Cincotta, Mark Shapiro, Ignacio Duran, Anna Berkenblit
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 29 Issue 13 Pg. 1750-6 (May 01 2011) ISSN: 1527-7755 [Electronic] United States
• PMID: 21444868 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Interferon-alpha
• temsirolimus
• TOR Serine-Threonine Kinases
• Sirolimus

Topics

• Antineoplastic Agents (adverse effects)
• Carcinoma, Renal Cell (complications, drug therapy, mortality)
• Humans
• Incidence
• Interferon-alpha (therapeutic use)
• Kidney Neoplasms (complications, drug therapy, mortality)
• Pneumonia (diagnostic imaging, epidemiology)
• Randomized Controlled Trials as Topic
• Sirolimus (adverse effects, analogs & derivatives)
• TOR Serine-Threonine Kinases (antagonists & inhibitors)
• Tomography, X-Ray Computed