Carboplatin and paclitaxel in non-small cell lung cancer: The role of amifostine

Lung cancer remains the leading cause of cancer deaths in industrialized countries. Efforts toward the development of new cytotoxic drugs and more active combination regimens for non-small cell lung cancer (NSCLC) are ongoing. Nevertheless, specific targeting of malignant cells poses a major challenge; toxicities of normal tissues continue to be dose limiting. Cytoprotective agents, such as amifostine (Ethyol; Alza Pharmaceuticals, Palo Alto, CA/US Bioscience, West Conshohocken, PA), that can shield normal tissues from cytotoxic effects are now the subject of intense clinical investigation. Amifostine has been shown to selectively protect normal tissues when used in combination with a large number of chemotherapeutic agents, including cisplatin, carboplatin, and paclitaxel. The addition of amifostine to paclitaxel or carboplatin has been shown to reduce the dose- limiting toxicities associated with each chemotherapeutic agent. However, now the combination regimen of carboplatin/paclitaxel is commonly used in NSCLC. To improve the tolerance of this regimen, a large, phase III, multicenter, randomized trial has been initiated that compares carboplatin/paclitaxel with or without amifostine in patients with locally advanced and metastatic NSCLC. The main objective is to evaluate the impact of amifostine on myelotoxicity and neurotoxicity. The addition of cytoprotective agents such as amifostine to other active NSCLC regimens may also reduce overall toxicity and improve the therapeutic index.