Drug-Related Pneumonitis in Patients With Advanced Renal Cell Carcinoma Treated With Temsirolimus

• Published in: Journal of clinical oncology Vol. 29; no. 13; pp. 1750 - 1756
• Main Authors: Maroto, Jose Pablo, Hudes, Gary, Dutcher, Janice P, Logan, Theodore F, White, Charles S, Krygowski, Mizue, Cincotta, Maria, Shapiro, Mark, Duran, Ignacio, Berkenblit, Anna
• Format: Journal Article
• Language: English
• Published: United States American Society of Clinical Oncology 01.05.2011
• Subjects: Antineoplastic Agents - adverse effects; Carcinoma, Renal Cell - complications; Carcinoma, Renal Cell - drug therapy; Carcinoma, Renal Cell - mortality; Humans; Incidence; Interferon-alpha - therapeutic use; Kidney Neoplasms - complications; Kidney Neoplasms - drug therapy; Kidney Neoplasms - mortality; Pneumonia - diagnostic imaging; Pneumonia - epidemiology; Randomized Controlled Trials as Topic; Sirolimus - adverse effects; Sirolimus - analogs & derivatives; Tomography, X-Ray Computed; TOR Serine-Threonine Kinases - antagonists & inhibitors
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2010.29.2235

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 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. 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. Patients with ARCC receiving temsirolimus should be monitored closely for development of pneumonitis, and their management should be altered if clinical symptoms appear.