Etoposide
Etoposide is a topoisomerase II inhibitor. This agent is used primarily in the treatment of small cell lung cancer. The most common pulmonary toxicity is a hypersensitivity reaction that can present with symptoms of anaphylaxis, angioedema, chest discomfort, bronchospasm, and hypotension. Etoposide-induced acute pneumonitis or acute lung injury, although uncommon, may occur. The pathology of etoposide-induced lung injury is diffuse alveolar damage, fibrin membrane formation, and alveolar wall edema. Fatal cases are rare. Etoposide is also known to increase the risk of radiation pneumonitis. Concurrent treatment with other pneumotoxic agents may increase the risk of pneumonitis. Zimmerman et al reported that interstitial pneumonitis developed in 24% of 50 patients treated with etoposide, methotrexate, and cyclophosphamide for small cell anaplastic lung cancer. It has been shown that etoposide increases the intracellular levels of methotrexate. The authors postulated that the pulmonary toxicity was secondary to methotrexate pneumonitis, which was caused by excessive intracellular levels of methotrexate related to the concurrent use of etoposide.
Teniposide
Teniposide is used in the treatment of glioblastoma multiforme. Hypersensitivity reaction to teni-poside occurs in 3.6 to 6.5% of patients. urticaria, hypotension or hypertension, dyspnea, bronchos-pasm, cyanosis, flushing, and vomiting within first 10 to 20 min of teniposide infusion develop in patients. In patients with leukemia, infusion reaction tends to occur after the completion of infusion. However, the timing of the hypersensitivity reaction is unpredictable and may occur during the first treatment cycle or during subsequent treatment cycles.
Rapamycin Analogs
Temsirolimus
Temsirolimus is a rapamycin analog that is active against renal cell carcinoma, endometrial carcinoma, breast cancer, glioblastoma multiforme, and GI neuroendocrine tumors. Temsirolimus binds with im-munophilin FK-506 binding protein-12 and forms a complex that inhibits the protein activity of mammalian target of rapamycin (mTOR). mTOR is a serine-threonine kinase that regulates cell growth, proliferation, and apoptosis. Interstitial pneumonitis is a non-dose-dependent complication of temsirolimus. Interstitial pneumonitis has been reported in 1 to 36% of patients treated with 25 to 250 mg/wk. The onset of pneumonitis usually takes place within 16 weeks (range, 2 to 16 weeks) after temsirolimus treatment. In one case series, 50% of patients were clinically asymptomatic, with drug-induced pneumonitis diagnosed by chest imaging. The chest CT scan may show ground-glass opacity or consolidation.
Everolimus
The pharmacologic effects of everolimus are also mediated through binding to FK-506 binding protein-12 and the inhibition of mTOR. Everolimus has been used as an immunosuppressive agent following organ transplantation, to treat severe psoriasis, and as an investigational antineoplastic agent (eg, for the treatment of sarcoma or renal cell cancer). Although clinical data in patients with malignancy are sparse, in one study using everolimus in heart transplant recipients, interstitial pneumonitis developed in 3.3% of patients 4 weeks after switching treatment to everolimus. All patients with pneumonitis required mechanical ventilation.