The Possibility of Traditional Chinese Medicine as Maintenance Therapy for Advanced Non-small Cell Lung Cancer

Xu Wr, Yang Gw, Xu Ym, et al. Evidence-Based Complementary and Alternative Medicine. Volume 2014 (2014) http://dx.doi.org/10.1155/2014/278917 Lung cancer has become the leading cause of cancer deaths, with nonsmall cell lung cancer (NSCLC) accounting for around 80% of lung cancer cases. Chemotherapy is the main conventional therapy for advanced NSCLC. However, the disease control achieved with classical chemotherapy in advanced NSCLC is usually restricted to only a few months. Thus, sustaining the therapeutic effect of first-line chemotherapy is an important problem that requires study. Maintenance therapy is given for patients with advanced NSCLC if three is no tumor progression after four to six cycles of first-line platinum-based chemotherapy. However, selection of appropriate maintenance therapy depends on several factors, while traditional Chinese medicine (TCM) as maintenance therapy is recommended for all kinds of patients. It has been demonstrated that TCM can prolong the survival time, improve the quality of life (QOL), and reduce the side effects for advanced NSCLC. Although the trials we searched about TCM serving as maintenance therapy is only 9 studies, the results indicate TCM can prolong the progression free survival (PFS) and improve the QOL. So it is possible for TCM to be as maintenance therapy for advanced NSCLC. Lung cancer has become the leading cause of cancer deaths in both men and women [1, 2]. Nonsmall cell lung cancer (NSCLC) accounts for around 80% of lung cancer cases [3]. At diagnosis, approximately 70% of patients present advanced stage of malignancy, for which curative therapy will not be available. Chemotherapy, radiotherapy, and targeted therapy are the conventional treatment for advanced NSCLC, among which chemotherapy is the main one. Platinum based doublets chemotherapy is the standard of care for advanced NSCLC. However, the disease control achieved with classical doublets chemotherapy in advanced NSCLC is usually restricted to only a few months [4–6]. About 20–80% of NSCLC patients cannot receive second-line chemotherapy for multiple reasons, including poor compliance [7]. Maintenance therapy can suppress disease progression and provide the opportunity to receive additional treatment. Thus, sustaining the therapeutic effect of first-line chemotherapy is an important problem that requires study. In recent years, maintenance therapy has become a new treatment strategy that aims to sustain a reduced tumor size and relieve tumor-related symptoms, in contrast to conventional chemotherapy that aims to maximize tumor cell death [7]. Maintenance therapy is an option in the National Comprehensive Cancer Network (NCCN) Guidelines only for responding and stable disease patients. Many clinical studies of multiple regimens and modalities about maintenance therapy are currently underway, which has been shown to improve the progression free survival (PFS) [8, 9]. However, some concerns remain regarding the overall survival (OS) and quality of life (QOL) [10]. The application of these chemotherapeutic drugs and molecular targeted drugs in maintenance therapy increase the financial burden of cancer treatment, which is another concern of this therapy. Traditional Chinese medicine (TCM) has increasingly become popular in the west including in cancer patients [11]. It is estimated the United States National Cancer Institute (NCI) spends around $120 million each year on complementary and alternative medicine (including TCM) related research projects [12]. It has been demonstrated that TCM can alleviate the clinical symptoms, improve the QOL, and reduce the side effects [13]. It helps NSCLC patients to “survive with tumor.” So TCM is very suitable for maintenance therapy. In fact, TCM is widely used for NSCLC patients as consolidation therapy which actually includes TCM maintenance therapy. The difference is that maintenance therapy is between first-line and second-line therapy. TCM is endowed with new meaning as the introduction of the concept of maintenance therapy. If the disease is not progressed after first-line therapy, the tumor will be suppressed temporarily. The progression of the tumor is inevitable as time goes by. It is possible to stabilize the tumor, prolong the time to progression, and improve the QOL given with TCM maintenance therapy. Moreover, maintenance therapy is only recommended for patients with performance status (PS) 1-2, while TCM maintenance therapy is recommended for all kinds of patients no matter PS 1-2 or PS 3-4. So it is possible for TCM to be as maintenance therapy for advanced NSCLC. We searched the following sources up to March 2014 using PubMed, CNKI (China National Knowledge Infrastructure), Wanfang Database. Keywords searched were “maintenance therapy” “wei chi zhi liao”, “nonsmall cell lung cancer” “fei xiao xi bao fei ai” or “NSCLC.” No language restriction was applied. After screening titles and/or abstracts, 9 articles were included involving TCM as maintenance therapy in the treatment of advanced NSCLC from the electronic and manual searches. These trials were all conducted in China and published in Chinese. The characteristics of the 9 trials were summarized in Table 1. Most of these trials are small sample, randomized controlled studies. The results indicate that TCM as maintenance therapy can improve the QOL. Part of the studies show that TCM can prolong the PFS compared with the control group (follow-up group). Among them, one study shows that TTP in TCM group is equivalent to that of chemotherapy group, but shows better QOL. Furthermore, there is another study with 162 patients involved from 1992–2007 [14]. It is a nonrandomized controlled study aiming to evaluate the efficacy of TCM as consolidation treatment after conventional therapy. 162 IIIA-IV NSCLC patients after conventional therapy were assigned into TCM group (decoction was applied after conventional therapy) and control group (follow-up after conventional therapy). The results showed that the 2-year and 3-year survival rate of TCM group were much higher than those of the control group. The MST of TCM group was 18 months, while that of control group was 12 months. So it supports that TCM as consolidation therapy can prolong the MST and improve the 2-year, 3-year survival rate. Although the IIIA-IV NSCLC patients after conventional therapy were included into this trial, which did not meet the criteria of maintenance therapy (advanced NSCLC after first-line chemotherapy with no tumor progression), it suggested that advanced NSCLC patients can benefit from TCM consolidation therapy to some degree. Summary Maintenance therapy with chemotherapy or targeted agents can prolong the PFS of advanced NSCLC patients to some degree, but chemotherapy may increase the toxicity and the risk of drug resistance, and targeted therapy is very expensive and only suited for certain patients with specific genetic alternation [43]. So some patients lose the opportunities to accept maintenance therapy. TCM is widely used in China for cancer patients. Although the effects of TCM in eradicating cancer cells are not obvious, it helps cancer patients to fight against cancer and restore the body into a balanced state by regulating the balance of yin and yang. 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