Small cell lung cancer and non-small cell lung cancer are distinctly different in etiology, germline genesis, histopathology and clinical aspects. Small cell lung cancer (SCLC) accounts for about 20-25% of lung cancers, and according to recent epidemiological data, this type has a decreasing trend [1].SCLC is derived from the malignant transformation of lung Kulchitsky cells, which are subdivided into oat cell type, intermediate cell type and mixed cell type by WHO [2]. The disease is more prevalent in males than females; the site of onset is predominantly the large bronchi (central type). The clinical characteristics are: short multiplication time and rapid progression of tumor cells, often accompanied by endocrine abnormalities or carcinoid syndrome; since patients have early hematogenous metastasis and are sensitive to radiotherapy, the treatment of small cell lung cancer should be mainly systemic chemotherapy, combined with radiotherapy and surgery as the main treatment means. Combination therapy is the key to successful treatment of small cell lung cancer. According to the US NCCN guidelines, the first-line chemotherapy regimens for SCLC include ① limited-stage EP regimen (DDP/VP-16), CE regimen (CBP/VP-16), and combined with radiotherapy. These regimens are often used in China and have achieved good efficacy. In addition to the EP and CE regimens, the DDP/CPT-11 regimen can also be used in the extensive stage. If the tumor recurs within 3 months and the patient is in good health, paclitaxel, doxorubicin, gemcitabine and isocyclophosphamide can be considered; if the tumor recurs more than 3 months, topotecan, irinotecan, CAV regimen (CTX/ADM/VCR), gemcitabine, oral VP-16 or norviben can be considered. If the tumor has recurred for more than 6 months, the first-line treatment regimen can still be maintained. See attached. There is no doubt that radiotherapy and chemotherapy are more effective in SCLC than in non-small cell lung cancer (NSCLC). For patients with extensive stage SCLC treated with standard chemotherapy regimens, their median survival time is 8-10 months; the 2-year survival rate is approximately 10-15%. Despite the high efficiency of chemotherapy for SCLC, the median time from the onset of chemoresistance to patient death remains unsatisfactory for patients with extensive-stage SCLC. For patients with limited-stage SCLC, 75%-80% of recurrence still occurs after induction chemoradiotherapy, so second-line treatment is the bottleneck and focus of SCLC treatment. 1. Is second-line chemotherapy effective for SCLC? The effectiveness of second-line treatment for SCLC needs to be studied in a multicenter randomized study of relapsed patients. Whether second-line chemotherapy regimens are superior to supportive care has been seen in the lung cancer literature in only one set of clinical trials with survival benefit [2], which involved 108 evaluable SCLC patients. Initial treatment randomized patients to 2 groups receiving 4 or 8 cycles of CVE (CTX, VCR, VP-16) regimen chemotherapy, respectively. Patients who relapsed were re-randomized into 2 groups to receive supportive therapy and second-line therapy (MTX, ADM), respectively. The results of this study showed that for patients treated initially with only short-term (4 cycles) therapy, survival was significantly shorter after relapse with supportive therapy than in the second-line chemotherapy group (median survival was 30 weeks, compared with 39 weeks in the other 3 groups, P < 0.01). 2. How to choose the second-line treatment plan for patients with recurrent SCLC? The efficiency of second-line chemotherapy for patients with recurrent SCLC depends mainly on the time from remission after first-line treatment to tumor recurrence. Patients who do not respond to first-line therapy or who are in remission for less than 3 months after first-line therapy are highly resistant and usually do not respond to any cytotoxic drugs, and these tumors are called "refractory" SCLC [3]. The aim of first-line therapy is to kill chemotherapy-sensitive cells, and once progression occurs early, it indicates that there are fewer chemotherapy-sensitive tumor cells and more drug-resistant cells. The salvage treatment of refractory tumors has a drug efficiency of less than 10% and survival is usually weeks after second-line treatment [4]. On the other hand, if the time between remission and progression is longer than 3 months, the efficacy of second-line therapy can be increased [5], and these tumors are also called "sensitive" SCLC, whose efficiency is likely to increase with the time between remission and progression. Ebi et al. analyzed 159 patients with SCLC who received multiple first-line regimens, of which 123 (77%) were effective [6]. Of the effective patients, 88 patients relapsed, 48 of whom received salvage second-line chemotherapy, and 16 (33%) were effective. Several papers have shown that the length of remission after chemotherapy, the time to the end of chemotherapy, and the efficiency of first-line treatment all have a significant impact on survival time. The extent of the lesion at the time of first-line chemotherapy, the combination of first-line chemotherapy with radiotherapy, and the patient's physical status (PS) at the time of first-line chemotherapy had no effect on outcome. 26 of the 48 patients with a PS of ECOG 3-4 at the time of second-line treatment had no effect. In contrast, patients with a PS of ECOG 0-1 had an efficiency of 45% and 39%. This shows that the better the physical condition, the better the efficacy of the treatment. Another factor affecting the efficacy of second-line chemotherapy is the combination of chemotherapeutic agents and the type of regimen used in the induction of remission. CTX-based chemotherapy regimens, such as CAV (CTX/ADM/VCR) or CAE (CTX/ADM/VP-16), are the traditional regimens for the treatment of SCLC [7]. The expected efficacy rate after treatment with CAV/CAE + DDP for patients with sensitive SCLC who have relapsed is 40-50% [8] [9]. On the other hand, CAV chemotherapy regimen has a lower efficacy in SCLC patients who have been initially treated with EP (VP-16+DDP) regimen chemotherapy.