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Current Status of Small Cell Lung Cancer in China

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Current Status of Small Cell Lung Cancer in China Central Journal of Cancer Biology & Research Review Article Special Issue on Current Status of Small Cell Lung Lung Cancer China *Corresponding author Cancer in China Ying Cheng, Division of Thoracic Oncology, Jilin Province Cancer Hospital, No.1018, Huguang Road, Jingjing Liu, Ying Cheng *, Hui Li and Shuang Zhang Chaoyang Borough, Changchun, China, Tel: 0086- Division of Thoracic Oncology, Jilin Province Cancer Hospital, China 431-85872688; Email: Submitted: 29 January 2014 Abstract Accepted: 04 March 2014 In China, Small Cell Lung Cancer (SCLC) accounts for over 15% of lung cancers. Published: 15 March 2014 Until now, the morbidity of SCLC has been increasing due to the ineffective smoking Copyright cession in China. Following the Chinese Guidelines of SCLC, the treatment of SCLC in © 2014 Cheng et al. China has been getting more and more standardized, which leads to the mortality of Chinese SCLC reaching the worldwide average. Although the outcomes of patients with OPEN ACCESS SCLC has been limited improved, the Chinese scholars have made many attempts for the treatment of SCLC including emphasizing lung screening, accurate disease staging, Keywords multidisciplinary team-work, as well as actively translational medical research. Multi- • Small cell lung cancer center clinical studies regarding to amrubicin hydrochloride, lobaplatin, endostar and • Clinical trial ipilimumab have been launched, as well as controversial problems for radiotherapy • Translational medicine research and surgery on SCLC. In addition, translational medicine researches on Circulating • Multidisciplinary treatment Tumor Cells (CTCs), Myeloid Suppression Cells (MDSCs) and next generation sequencing have been conducted to explored novel drive genes and prognostic markers of SCLC, which will provide more evidence to guide the diagnosis and treatment of SCLC. ABBREVIATIONS sensitive to chemotherapy and radiotherapy, SCLC patients are liable to relapse and often present with drug resistance. SCLC: Small Cell Lung Cancer; NSCLC: Non-Small Cell Lung Cancer; LS-SCLC: Limited-Stage Small Cell Lung Cancer; In Europe and America, SCLC incidence has decreased ES-SCLC: Extensive-Stage Small Cell Lung Cancer; DNA: through the implementation of tobacco control, but the number Deoxyribonucleic Acid; AP: Amrubicin in Combination with of female patients is increasing, leaving the current prevalence Cisplatin; EP: Etoposide in Combination with Cisplatin; OS: of males to females as 1:1 [7]. There has been little progress Overall Survival; PFS: Progression-Free Survival; ORR: Overall in the development of therapeutic approaches for SCLC in the Response Rate; EL: Lobaplatin Combined Etoposide; TTP: Time To Progression; ASCO: American Society of Clinical Oncology; improved for the past 15 years [8]. past 30 years [7], and overall survival has not been significantly CR: Complete Response; PR: Partial Response; SD: Stable Lung cancer incidence has been increased in China due Disease; PCI: Prophylactic Cranial Irradiation; IFRT: Involved- to huge Chinese populous in the world and a large number of Field Radiotherapy; CT: Computed Tomography; INF: Isolated Nodal Failure; MST: Median Survival Time; CTCs: Circulating that in 2009 the incidence rate was 53.57/10 million and ranks Tumor Cells; MDSCs: Myeloid Suppression Cells; UGT1A1: UDP- topsmokers. one in 2012 all malignant Chinese Cancer diseases, Registry top one Annual in male Report patients, identified and Glucuronosyltransferase 1A1; CSCLC: Combined Small Cell Lung top two in female ones; the mortality rates was 45.57/10 million Cancer. and top one among in overall malignant diseases [9]. According INTRODUCTION to GLOBOCAN, there are 3,065,000 newly diagnosed lung cancer cases in China in 2012, accounting for 22% of worldwide cases. Lung cancer is the most common malignancy worldwide. In Recently, the proportion of newly SCLC cases in China has been 2012, the reported morbidity and mortality rates are as high changed due to aid of newly advanced technologies in diagnosis as 13% (1.8 million) and 19.4% (1.6 million), respectively [1]. regarding to cytological and pathological detection, as well as the Approximately 15% of lung cancer cases are Small Cell Lung changes of lung cancer patients’ number. Different from Western Cancers (SCLCs), which are highly related to smoking [2,3]. SCLC countries, there are not very effective policies in China to reduce is a very invasive, fast-growing cancer that distinctly differs from tobacco consumption, thus the incidence of SCLC, especially in other cancers in its histological and clinical features, response to the north, is still increasing in line with the increasing number of treatment and therapeutic strategy. SCLC often spreads rapidly; smokers. Considering the sex ratio, SCLC is slightly more common approximately 70% of cases present with metastases at diagnosis, in men than in women. and the median overall survival rate is only 8–11 months with a 5-year survival rate of less than 5% [4-6]. Although being Although translational researches on diagnosis and treatment Cite this article: Liu J, Cheng Y, Li H, Zhang S (2014) Current Status of Small Cell Lung Cancer in China. J Cancer Biol Res 2(1): 1032. Cheng et al. (2014) Email: Central for SCLC have not been developed as fast as that for Non-Small meeting in 2013 and the Chinese Society of Clinical Oncology Cell Lung Cancer (NSCLC), Chinese scholars have made great annual meeting in 2012, respectively. progress in the diagnosis and treatment of SCLC in pace with As cisplatin has distinct dose-limiting toxicity on renal, the increasing social and public attention. Here we present the ear, neuron and gastrointestine, drug resistance induced by treatment progress made in Chinese patients with SCLC. treatment and other side-effects, its long-term and wide clinical Medical treatment of SCLC in China application is restricted. Chinese researchers have been actively exploring new platinum drugs and various regimens for more Because SCLC is rarely operable, chemotherapy is the priority for treatment. Combinational chemotherapy is effective in 85– 95% in limited-stage SCLC (LS-SCLC) with 50–60% patients inefficient, China lowerin 2005, toxicity, is currently and no in cross-resistance. the research stage, Lobaplatin, showing a showing a complete response and 60–80% in Extensive-Stage similarthird-generation toxicity platinum-basedto carboplatin anticancerand no cross-resistancedrug first marketed to SCLC (ES-SCLC) [10]. For decades, chemotherapeutic drug cisplatin.. The results of clinical study showed that the ORR of development for SCLC has been slowly, leaving etoposide and Lobaplatin combined Etoposide (EL) for advanced SCLC can be cisplatin as the standard chemotherapy for a long time [11,12] Besides, only irinotecan is recommended by the National and EL with respect to median Time To Progression (TTP) and Comprehensive Cancer Network (NCCN) guidelines as a standard one-yearup to 92% survival [17]. There rate. wasBase no on significant the good differenceprospect of between lobaplatin EP in the treatment of SCLC, from September 2010, Cheng, as been attempting some new drugs for SCLC, including topotecan, first-line therapy for ES-SCLC [13]. Chinese researchers have main principle investigator, started a prospective, randomized, teniposide, nedaplatin, oxaliplatin etc, however most of them are positively controlled, multi-center clinical trial (HNCA002) in single-center and small-size studies. China (registration number: ChiCTR-TRC-10001047). This study Numerous clinical studies on new drugs have been conducted in recent years relying on very rich resource of Chinese patients, regimen (etoposide-lobaplatin) with EP regimen (etoposide- which also gradually improve Chinese clinical study, NSCLC is cisplatin)aims to compare for ES-SCLC. the effective, A total of safety 14 research and tolerance centers profileparticipated of EL the main target in clinical researches and achieved more than in this study. This study has been completed with a total of 240 SCLC did. Amrubicin has shown promising for the treatment cases enrollment and the results are processed at present. of SCLC. Amrubicin, a synthetic anthracycline, can inhibit Besides chemotherapeutic drugs, the Chinese scholars topoisomerase II and relax supercoils of deoxyribonucleic acid have also explored targeted drugs. Endostar is a new kind of (DNA) for replication. Data from Japanese researchers showed biological products under the category of angiostatins, which has broad-spectrum antimicrobial and anti-angiogenesis effects. approved in Japan in 2002 and is applicable for treatment of lung amrubicin has good efficacy and tolerance [14,15]. It was first Endostar inhibits angiogenesis in tumor by inhibiting the cancer including SCLC and NSCLC. Clinical trials of amrubicin migration of endothelial cells to form blood vessels and cutting in Western patients showed that it is not inferior to standard off the nutrition supply to tumor, as well as inhibiting tumor proliferation and transfer. As Endostar shows good effects on 2008 to July 2010, Sun et al. organized a phase III clinical trial to regimen in the first-line and second-line treatment. From June NSCLC treatment, Chinese scholars also hope it would show compare the effects of amrubicin in combination with cisplatin great effects on SCLC. Zhou et al reported the results of a pahse (AP) and etoposide in combination with cisplatin (EP) in patients study using cisplatin/etoposide and endostar for ES-SCLC with previously untreated
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