Novel Antineoplastic Agents for Solid Tumors: Monoclonal Antibodies

Bevacizumab

Bevacizumab, a monoclonal antibody against endothelial growth factor, has been used to treat patients with a variety of cancers. There are several reported pulmonary toxicities associated with bevaci-zumab therapy. Pulmonary hemorrhage and hemoptysis has been reported in 2.3% of patients with nonsquamous NSCLC. In these patients, pulmonary hemorrhage may lead to respiratory failure, and fatalities have been reported in 1.6% of patients treated with bevacizumab. Severe hemoptysis and pulmonary hemorrhage associated with bevacizumab therapy is more common in patients, with squamous cell carcinoma being reported in up to 31% of patients. Bevacizumab has also associated with increased risk of deep venous thrombosis (DVT) and pulmonary embolism.

Matuzumab

Matuzumab is a humanized Ig G1 that blocks the activation of EGFR. Matuzumab is active against EGFR-positive NSCLC. Bronchospasm related to matuzumab has been reported in 5% of patients. Premedication with corticosteroids is effective to prevent bronchospasm.

Trastuzumab

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Trastuzumab is a humanized monoclonal antibody that selectively binds to the human EGFR (HER)-2 protein. Trastuzumab is indicated for the treatment of metastatic breast cancers with overexpression of HER-2 protein. The incidence of trastuzumab-induced pneumonitis is 0.4 to 0.6%. Trastuzumab-induced pneumonitis may present with rapidly progressive pulmonary infiltrates and respiratory failure after receiving 1 dose of trastuzumab or after 6 weeks of therapy. The mortality of trastuzumab-induced pneumonitis is about 0.1%. Acute neutrophilic alveolitis and organizing pneumonia after tras-tuzumab treatment also have been reported. Infusion-related symptoms, including hypotension, angioedema, bronchospasm, dyspnea, fever, chills, and urticaria, has been reported to occur in about 15% of patients. Severe episodes of hypotension, bronchospasm, and hypoxemia leading to death are rare.

Nucleoside Analogs

Gemcitabine

Gemcitabine is a nucleoside analog with activity against a variety of solid tumors, especially NSCLC and pancreatic cancer. A variety of forms of pulmonary toxicity have been described with the use of gemcitabine. Dyspnea developing within hours of infusion has been reported to occur in about 10% of patients. Most patients improve with therapy with diuretics and corticosteroids. Bronchospasm develops in about 0.6% of patients. These infusion-related reactions are usually mild and rarely have resulted in the discontinuation of treatment. Gemcitabine-induced pneumonitis has been reported to occur in up to 13.8% of patients. An analysis’ of pooled data from a large database showed the incidence of gemcitabine-induced pulmonary toxicity to vary from 0.02 to 0.27%. The following three types of gemcitabine-induced pneumonitis have been described: (1) a capillary leak syndrome with pulmonary edema; (2) diffuse alveolar damage; and (3) alveolar hemorrhage. Previous lung disease, chest radiation, and concurrent treatment with other agents (eg, paclitaxel, docetaxel, ifosfamide, or granulocyte colony-stimulating factor) are possible risk factors. Restrictive physiology with a marked reduction in diffusion capacity has been reported. Although the mortality rate can be as high as 20%, a rapid response (within days) to prednisone 60 mg daily (you can buy in our store prednisone), has been described in the literature.