TCM Combined Chemoradiotherapy in the Treatment of Limited-Stage Small Cell Lung Cancer: Current Status and Perspectives

About 13% of lung cancer cases are of the small cell subtype, but this variant is highly aggressive, and approximately 40% of patients with small cell lung cancer will have limited-stage disease, which is potentially curable with the combination of chemotherapy and radiation therapy. The standard therapy for limited-stage small cell lung cancer is concurrent chemoradiotherapy, and the 5-year survival rate observed in clinical trials is approximately 25%. For patients who obtain a near complete or complete response, prophylactic cranial irradiation (PCI) reduces the incidence of brain metastases and improves overall survival. However, chemotherapy has its limitations, the side effect caused by chemotherapy and radiotherapy is critical, so extending patient lifespan by using treatments with lower toxicities is necessary. TCM plays an important role in improving quality of life and a reduction in side effects. This may be of significant clinical value in prolonging patient’s survival time. Small cell lung cancer (SCLC) is characterized by rapid growth, a high prevalence of mediastinal lymph node and distant metastases at the time of diagnosis. Patients with very early stage could take the lump resection, while most patients with SCLC are not considered to be candidates for surgery. SCLC is one of the most chemosensitive solid tumors, and the outcome of SCLC patients is surely improving but slowly. Chemoradiotherapy plays a very important role in the treatment of patients with limited-stage SCLC (LS-SCLC). The chemotherapy consisting of cisplatin plus etoposide and concurrent twice-daily thoracic radiotherapy has yielded a 5-year survival rate of approximately 25% in LS-SCLC patients [5,6], which also became the standard chemoradiotherapy regimen worldwide. Prophylactic cranial irradiation (PCI) is used for patients with LS-SCLC who have achieved a complete or near complete response following initial therapy, as it decreases the risk of brain metastases and provides an overall survival benefit. However, the adverse effect caused by chemotherapy and radiotherapy is serious; TCM combined with chemotherapy demonstrated significant improvements in quality of life and a reduction in anemia and neutropenia [7]. Because of its low cost and toxicity, and high effectiveness [8,9], TCM is often used in cancer patients who have finished conventional treatment, such as surgery, chemotherapy, Introduction Lung cancer has become the most common cancer and the leading cause of cancer-related death in the world [1]. In 2010, both the incidence and mortality rates of lung cancer in China ranked first among all malignancies [2]. Lung cancer is one of the most common carcinomas not only in China, but also in the United States and Europe. It is estimated that approximately 13% of the 219,000 patients who receive a diagnosis of lung cancer will have small cell histology [3,4]. ISSN: 2378-3419 DOI: 10.23937/2378-3419/1410124 He et al. Int J Cancer Clin Res 2019, 6:124 • Page 2 of 4 • who had received different therapies, 55 had received concurrent radiochemotherapy, 66 received sequential radiochemotherapy, and 50 received chemotherapy alone. For the concurrent group, sequential group, and chemotherapy alone group, the median overall survival (OS) were 30.6, 23.1, and 19.1 months, the median progression-free survival (PFS) were 19.7, 13.3, and 11.5 months, and the 5-year survival was 28.7%, 13.6%, and 9.4%, respectively (all P < 0.05). The main toxic effects were myelosuppression, radiation pneumonia, and radiation esophagitis. The incidences of I-II grade myelosuppression were 92.7%, 89.4%, and 92% in the concurrent group, sequential group, and chemotherapy alone group (P = 0.25). For concurrent group and sequential group, the incidence of I-II grade radiation pneumonia were 47.2% and 50%, whereas the incidence of I-II grade radiation esophagitis were 94.5% and 75.8%. Bing Xia, et al. [19] performed a quantitative analysis of tumor shrinkage due to chemotherapy and its implication for radiation treatment planning in limited-stage small-cell lung cancer, which suggests that the first cycle of chemotherapy is very important for tumor shrinkage and that initiating thoracic radiation therapy at the second cycle of chemotherapy may be a reasonable strategy for timing of radiation therapy in LS-SCLC treatment. PCI for limited-stage small cell lung cancer Despite a high response to chemotherapy and radiation therapy, most patients suffer from local recurrence or/and distant metastasis within 2 years [20]. Brain metastases are the most common site of distant failure in patients with SCLC, regardless of disease stage at presentation. The prevalence of brain metastases detected at the time of diagnosis ranges from 10% to 24% and the probability of developing brain metastases during the metastasis is associated with a poor prognosis and the median survival after the development of BM is only 4-6 months [21-23]. The positive role of PCI in patients with limited SCLC and extensive SCLC who achieve a complete response (CR) to chemotherapy was established in 1999 by a meta-analysis that included data from seven randomized prospective studies comparing PCI with no PCI after a CR [24]. Studies considered pivotal in supporting the use of PCI have been identified in three meta-analyses [25-27] and two current national guidelines [28,29]. Studies in TCM combined chemotherapy Chemotherapy is highly responded to patients with limited disease, but chemotherapy alone is prone to induce relapse and metastases, with a high rate of loco-recurrence. The traditional treatment of SCLC is chemoradiotherapy, but the side effects are serious, which may also lead to the failure of completion of chemoradiotherapy. Traditional Chinese Medicine (TCM) has been used for thousands of years and play or radiotherapy and acts as a maintenance treatment. In this review, we will mainly focus on the TCM combined therapeutic options currently available for the management of the patients who have LS-SCLC at diagnosis.