ABSTRACT
Lung cancer is the leading cause of cancer death in men and its incidence is rising worldwide. In the United States, lung cancer-related mortality exceeds that of breast cancer in women (1,2). A clear relationship between cigarette smoking and lung cancer incidence and mortality has been demonstrated (3). There are four major histological subtypes of lung cancer: adenocarcinoma, large cell carcinoma, squamous cell carcinoma, and small cell carcinoma. Around 1970, it became apparent that different treatment modalities were necessary for the different types of tumor. Squamous cell carcinoma, adenocarcinoma, and large cell carcinoma are generally referred to as nonsmall cell lung cancer (NSCLC). Although chemotherapy is increasingly being used in clinical trials in NSCLC, the only treatment modality offering real chances for longterm survival is surgery. In contrast, small cell lung cancer (SCLC), accounting for approximately 20% of the lung carcinomas, is more sensitive to both radiotherapy and chemotherapy than NSCLC both in patients and in tumor model systems (1,2,4). In SCLC-unlike NSCLC-surgery offers a solution in only a small minority of patients (5). Subsequently, chemotherapy has become the cornerstone of treatment for this disease. In the late 1960s, the first randomized placebo-controlled trial with cyclophosphamide demonstrated improvement of survival in patients with SCLC (6). Several cytotoxic drugs have demonstrated efficacy, some of which (for instance, methotrexate and CCNU) have been replaced by more active drugs. It is generally accepted that combination chemotherapy should be used for the treatment of SCLC, because by this approach it is expected that the development of tumor cell resistance will be prevented or delayed. These combinations contain two or, in most cases, three active drugs. The most frequently used induction regimens are cyclophosphamide-doxorubicin-vincristine (CAY), cyclophosphamide-doxorubicin-etoposide (CDE), and cisplatin-etoposide (PE).
