Clinical Safety and Efficacy of Kanglaite ® ( Coix Seed Oil ) Injection Combined with Chemotherapy in Treating Patients with Gastric Cancer

Gastric cancer is one of the most frequent cancers in the world. The highest incidence and mortality rate are in Eastern Asia (Jemal et al., 2011). In China, gastric cancer has become a significant cancer burden and one of the key issues regarding cancer prevention and treatment. It was predicted that, in 2005, 0.3 million deaths and 0.4 million new cases from gastric cancer thus would rank the third most common cancer (Yang, 2006). The main treatment modalities for gastric cancer available are: surgery, chemotherapy, radiotherapy, immunochemotherapy, multimodality therapy etc. Chemotherapy is one of the treatment options available in advanced gastric cancer. It may relieve gastric cancer-related symptoms, improve quality of life and prolong survival in some patients who respond to treatment. How to increase efficacy and decrease toxicities of chemotherapy remains a focus in this area. Kanglaite® (Coix Seed Oil) Injection, which had been confirmed with anti-tumor activity, is one of Chinese herb Preparations that is developed and manufactured by Zhejiang Kanglaite Pharmaceutical Co., Ltd in China (Li 2005). It is mainly used for the treatment of no-small cell lung cancer, liver cancer, gastric cancer etc (Lian et al., 2006; Zhu et al., 2009). We hypothesize that it


Introduction
Gastric cancer is one of the most frequent cancers in the world.The highest incidence and mortality rate are in Eastern Asia (Jemal et al., 2011).In China, gastric cancer has become a significant cancer burden and one of the key issues regarding cancer prevention and treatment.It was predicted that, in 2005, 0.3 million deaths and 0.4 million new cases from gastric cancer thus would rank the third most common cancer (Yang, 2006).The main treatment modalities for gastric cancer available are: surgery, chemotherapy, radiotherapy, immunochemotherapy, multimodality therapy etc. Chemotherapy is one of the treatment options available in advanced gastric cancer.It may relieve gastric cancer-related symptoms, improve quality of life and prolong survival in some patients who respond to treatment.How to increase efficacy and decrease toxicities of chemotherapy remains a focus in this area.
Kanglaite ® (Coix Seed Oil) Injection, which had been confirmed with anti-tumor activity, is one of Chinese herb Preparations that is developed and manufactured by Zhejiang Kanglaite Pharmaceutical Co., Ltd in China (Li 2005).It is mainly used for the treatment of no-small cell lung cancer, liver cancer, gastric cancer etc (Lian et al., 2006;Zhu et al., 2009).We hypothesize that it

Patient
All the patients were required to be pathologically diagnosed with gastric cancer, with Karnofsky performance status≥60, aged between 18 and 75 years, predicted survival time≥3 months.With adequate bone marrow (white blood cell count>4.0x109andplatelet count >100x109), and liver function (bilirubin and transaminases <2 times the upper limit normal), no heart and kidney disease, and signed an informed consent before chemotherapy.
Patients excluded from this study if they failed to complete two cycles of chemotherapy, with any serious medical or psychiatric condition, or other malignancies.Pregnant or lactating women are excluded from the study.

Treatment
In experimental group, Kanglaite ® Injection combined with DOC regimen, which consisted of docetaxel (D), oxaliplatin (O) and capecitabine (C).Docetaxel and

Efficacy Observation
Treatment efficacy was evaluated after more than two cycles of chemotherapy.Complete remission (CR), partial response (PR), stable disease (SD), and progressive disease (PD) were determined based on RECIST criteria (Eisenhauer et al., 2009).Quality of life was evaluated in accordance with the Karnofsky Scale (Clancey, 1995;Friendlander and Ettinger, 2009), designated increasing if the score increased by 10 after treatment, decreasing if the score decreased by 10 and otherwise stable.

Toxicity Assessment
Patients were assessed and graded for toxicity according to WHO criteria (Kaba et al., 2004).

Efficacy
Sixty patients fulfilled eligibility and had completed at least 2 cycles of treatment.All patients were divided into two groups.No statistically significant difference was found between two groups of patients regarding age, sex, and clinical stage (P > 0.05).
No CR was observed in all patients.The response rate in experimental group (CR+PR) was 40%, while that in control group was 16.7%, with statistically significant difference (p<0.05).The clinical benefit rate of two groups (CR+PR+SD) were 86.7% (in experimental group), 66.7% (in control group) respectively, without statistical significance (p>0.05)(Table 1).

Quality of life before and after treatment
KPS score of experimental group increased in 15 cases (50%), 10 cases stable and 5 cases decreased, while that of control group increased in 6 cases (20%), 13 cases stable and 11 cases decreased.The difference between two groups was statistically significant (p<0.05)(Table2).

Toxicity
All patients underwent toxicity assessment.Treatment related side effects were reversible, and no termination of chemotherapy or death caused by adverse events occurred.the main adverse effects were bone marrow suppression, gastrointestinal symptoms, neurotoxicity, oral mucositis, and hand-foot syndrome etc.The statistical significance differences were discovered between two groups in terms of leukopenia (50% in experimental vs. 63.3% in control group), thrombocytopenia (30% in experimental vs. 43.3% in control group), diarrhea (33.3%in experimental vs. 46.7% in control group) and nausea/vomiting (53.3% in experimental vs. 66.7% in control group) (Table3).

Discussion
Gastric cancer chemotherapy was still not normalized and standardized.Chemotherapy could reduce the rate of recurrence and metastasis, and prolongs survival time.But, chemotherapy often brings about serious side effects.Therefore, how to reduce side effects of chemotherapy, in the meantime increase efficacy and improve quality of life have aroused more and more attention.It is a distinguishing feature of traditional Chinese medicine to contribute in this area.
The main ingredient of Kanglaite ® Injection is Coix seed oil, which has been used to treat cancers in Chinese traditional medicine (Yu et al., 2008;Yu et al., 2008).It can induce tumor cell apoptosis, block tumor cell mitosis, improve immune function, reduce the toxicity of chemotherapy, and relieve cancer pain etc.

Table 1 . Comparison of Treatment Efficacy in Two Groups n (%)
N, number cases; CR, Complete Remission; PR, Partial response; SD, stable disease; PD, progressive disease; *experimental group was chemotherapy combined with Kanglaite injection.which is developed and manufactured by Zhejiang Kanglaite Pharmaceutical Co., Ltd in China.Control group.control group was given chemotherapy alone *