A guide for small cell lung cancer, focusing on chemotherapy regimen selection for small cell lung cancer (SCLC) and the progress of clinical trials done so far. For all SCLC patients, chemotherapy is a fundamental component of treatment. Adjuvant chemotherapy is recommended for patients with surgically resected SCLC. For patients with limited stage SCLC and good PS (0-2), chemotherapy with concurrent chest radiotherapy (grade 1) is recommended. For patients with extensive stage, chemotherapy alone is recommended, although radiotherapy has been used for some patients for symptomatic relief. For patients with extensive stage and brain metastases, chemotherapy may be given before or after whole brain radiotherapy, depending on whether the patient has neurological symptoms. Single-agent or multidrug combination regimens have been used in patients with SCLC. Etoposide and cisplatin (EP) regimens are the most commonly used initial combination chemotherapy regimens, replacing alkylator/anthracycline-based regimens based on their efficacy and adverse effects in limited-stage disease.EP concurrent with thoracic radiotherapy is recommended for the treatment of patients with limited-stage SCLC (grade 1). In combination with chest radiotherapy, EP puts the risk of esophagitis, pulmonary toxicity and hematologic toxicity at increased risk. Bone marrow growth factor is not recommended for patients treated with concurrent chemoradiation. In clinical practice, carboplatin usually replaces cisplatin to reduce the risk of vomiting, neuropathy and nephropathy, but causes an increased risk of bone marrow suppression. Clinical trials have shown comparable efficacy of cisplatin and carboplatin regimens. There are many combination regimens evaluated in extensive stage SCLC, but the evidence supporting their superiority over EP regimens are rarely consistent. The combination of irinotecan and platinum-based agents presents the greatest challenge to EP regimens. A phase III study conducted in Japan showed that irinotecan + cisplatin resulted in a median survival of 12.8 months compared to 9.4 months with the EP regimen (p=0.002). However, two subsequent large phase III studies conducted in the United States also compared irinotecan + cisplatin versus the EP regimen and did not find differences in remission rates or OS. A phase III trial (n=220) found a slight improvement in OS with irinotecan + carboplatin compared to carboplatin + oral etoposide (8.5 vs 7.1 months, p=0.04). Based on these findings, the NCCN guidelines added the carboplatin+irinotecan regimen for the treatment of extensive disease. A number of strategies have been evaluated to improve outcomes in patients with extensive-stage SCLC, including the addition of a third agent to the standard two-drug regimen. In two trials, the addition of isocyclophosphamide (or cyclophosphamide + an anthracycline) to an EP regimen showed some survival benefit. However, these findings were not consistent, and the addition of an alkylating agent, with or without an anthracycline, significantly increased hematologic toxicity. Similarly, the addition of paclitaxel to cisplatin or carboplatin + etoposide showed some promise in phase II trials, but was not found to improve survival in phase III trials and also increased toxicity. Maintenance therapy or consolidation chemotherapy after 4-6 cycles may slightly prolong remission, but does not improve survival and also increases the risk of toxicity. Anti-angiogenic therapy has also been evaluated in patients with SCLC. In patients with limited-stage SCLC, a phase II study exploring the efficacy of simultaneous irinotecan, carboplatin, and bevacizumab radiotherapy followed by bevacizumab maintenance therapy was terminated early because of the high incidence of tracheoesophageal fistulae. In patients with extensive-stage SCLC, two phase II trials examined the efficacy of platinum-based chemotherapy in combination with bevacizumab, finding promise for remission rates and survival data. A phase III study is underway to determine whether the addition of bevacizumab improves outcomes in patients with extensive-stage SCLC. At this time, the NCCN guidelines do not recommend bevacizumab. In summary, current attempts to improve long-term survival by adding more drugs, using dose-enhancing chemotherapy regimens, maintenance therapy, and switching to non-cross-resistant chemotherapy regimens have not yielded significant advantages over standard therapy.