PURPOSE: mTOR is a key regulator of cell growth and proliferation, and the inhibitor sirolimus is in use for prevention of rejection in transplantation. Temsirolimus and everolimus are being increasingly studied and used as antineoplastic agents. Pneumonitis is a known complication of this class of drugs but there is limited data about the manifestation of pulmonary toxicity in the cancer population.
METHODS: Cases of pneumonitis reviewed by the pulmonary service believed to be secondary to mTOR inhibitors.
RESULTS: Two patients with documented pneumonitis are described; Four others with probable pneumonitis still on study. A 61 year old woman with gastrointestinal carcinoid receiving temsirolimus developed asymptomatic patchy focal infiltrates. Bronchoscopy showed inflammatory cells only and the patient was observed. After one year she remained asymptomatic, however infiltrates progressed. Bronchoscopy with a transbronchial biopsy showed organizing pneumonia and the patient was observed. Six months later she developed dyspnea with increased infiltrates (Figure 1). Prednisone was given with improvement and temsirolimus was continued at a reduced dose with stability. A 68 year old man received everolimus for metastatic renal carcinoma. Worsening dyspnea on exertion developed after five months with new bibasilar patchy infiltrates. Treatment was interrupted multiple times with improvement and recurrence of symptoms on restarting the mTOR inhibitor. Everolimus was discontinued with resolution.
CONCLUSION: Cancer patients on mTOR inhibitors developed a pneumonitis similar to that described for sirolimus. It appears to have a favorable prognosis with resolution if the drug is discontinued, reduced in dose or with the use of steroids. Frequent use of scanning in cancer patients, may allow increased detection of low grade pneumonitis or identification of progressive pulmonary adverse effects. It is important to distinguish these from metastatic disease.
CLINICAL IMPLICATIONS: With the increasing use of mTOR inhibitors in the transplant population as well as cancer patients, recognition of the presentation and course of pulmonary toxicity is essential.
DISCLOSURE: Shilpa DeSouza, No Financial Disclosure Information; No Product/Research Disclosure Information