Yufei Yang1*, Jianzhong Ge 1, Yu Wu1, Yun Xu1, Zhongning Guo1, Jianbin Wang1,
Jianping Liu 2
1 Department of Oncology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing (100091)
2 Center for Evidence-Based Medicine, Beijing University of Chinese Medicine, Beijing (100091)
In recent 10 years, a prospective cohort study with randomized controlled trial in reducing the relapse and metastasis of stage II & III colorectal cancer based on conventional Western medicine therapy (radical surgery, chemotherapy, and radiotherapy) have been conducted in Xiyuan hospital affiliated to China Academy of Chinese Medical Sciences and a conclusion with the guide of review and study on principle of differentiation of symptoms and signs has drawn. So far, the study is summarized as follows.
1. Review registered in Cochrane collaboration web of international center for evidence-based medicine. In 2002, we had registered the protocol, its title was “Herbal medicine for relapse and metastasis of postoperative colorectal cancer. (DWU054)” [1]. Norway national evidence-based medicine provided financial assistance to this project. A total of 4413 literatures were retrieved in nine databases. At last, eight randomized trials and one quasi-randomized trial were included in this review, among them one clinical trial was unequal randomization control trial that reported participants were assigned to groups according to criterion of 2:1[2]. One quasi-randomized trial described that the participants were assigned by sequence of visit [3]. There were 715 patients included in this review who were all Chinese. Among all of them, 451 subjects were male and 264 were female. According to TNM classification, there are 30 cases with stage I, 203 cases with stage II and 482 cases with stage III. Most of their age was from 50 to 70 years old. They all received radical colorectal operation and they had no signs of metastases. Eight trials clearly described the tumor position of all participants, it included 265 colon cancer and 349 rectal cancers. One trial only reported 101 patients with colorectal. The results also showed most of Chinese herbs had the capacity to improve quality of life and immune function, degrade adverse events caused chemotherapy/radiotherapy, and prevent the blood cell from descending. But because the quantity of clinical studies on herbs medicine for relapse and metastasis were less and their qualities of methodology were low, so the conclusion of systematic review for the herbal medicine for relapse and metastasis in patients operated for colorectal cancer was uncertain. It also needs randomized controlled trial of large sample size and high quality to test it.
2. In 2002, we also registered the protocol “Herbal Medicine for advanced colorectal carcinoma”, its number is DWU055 which was provided financial assistance from Norway national center for evidence-based medicine. A total of 4903 literatures were retrieved in 9 databases. 22 clinical trials were discussed by research group after reading title and abstracts. The result indicated that although the research method was deficient and no high quality of RCT trials, multiple centers and large sample were established, the evidence showed combined therapy of traditional and western medicine might have advantage to promote the objective remission rate in advanced stage patients. Because the quality of research method in RCT were comparatively low, distribute of prognosis factors were uneven, and publish bias existed, not a kind of therapy regimen was proved repeatedly, so we can’t draw positive conclusion and also can’t recommend concreted herbs for advanced colorectal cancer. With the development of research of advanced colorectal cancer, some new research will make up at the aspects of blindness, allocation concealment, and analysis function. Above conclusions will be gradually updated while they are referred to be as clinical decision analysis. Though we have finished many studies on herbs for advanced colorectal, only a few studies were included in this review due to low quality of research method. We also found that researchers of Chinese medicine didn’t pay attention to the methodology. Meanwhile, methods of Chinese medicine have made more progress of research method than before. It is urgent to promote the quality of methodology for clinical researchers.
3. With the help of national nature science foundation, we make a study on literature of colonic and rectal cancer. The license number of topic was 3057245. It is believed that occurrence of colorectal cancer is related to three viscera including spleen, lung, and liver and two organs including colon and rectum. Differentiation of symptoms and signs for classification of syndrome was initially formulated. It included syndrome of dryness of the intestine and deficient of saliva, syndrome of insufficiency of spleen and stomach, syndrome of piqikuixu, syndrome of ganyinkuixu, syndrome of shire neiyun, syndrome of in coordination between the liver and stomach, syndrome of deficiency of kidney-Qi, and syndrome of yangxu shiting. With the increase of TNM stage, there are tendency from organ to viscus and from superficies to interior. Sthenia syndrome was conspicuous in severe patients by TNM stage. KPS score of patients with asthenia syndrome was lower than patients with asthenia and sthenia syndrome. Aged patients easily suffered from asthenia syndrome, younger patients easily suffered from asthenia and sthenia syndrome.
4. Clinical RCT Research about QUXIE Capsule of T.C.M. in Improving the Median Survival Time and Qualify of Life for Advanced Colorectal Carcinoma. In order to evaluate the efficacy of QUXIE capsule in prolonging the median survival time and quality of life for advanced colorectal carcinoma. We designed a randomized controlled research program, 40 patients with advanced colorectal carcinoma were included. 2 patients were dropped out; 1 patient was excluded. 18 patients with advanced colorectal carcinoma were treated by routine methods including chemotherapy, radiotherapy and TCM of QUXIE capsule (treatment group); 19 patients in control group were treated by routine cancer treatment methods without QUXIE capsule (control group). Grades of TCM symptoms, quality of life and KPS were evaluated after 3 months treatment. Survival time, media survival time and existing condition of the patients were evaluated after long follow up period. Results: 2 patients died, and 16 patients are alive in treatment group; 8 patients died, and 11 patients are alive in control group (P<0.05), the media survival time of treatment group and control group are 17 months and 13 months respectively. The survival time and time to progression of treatment group and control group is 22.63±7.34 months VS 19.76±8.28 months (P<0.05) and 17.76±5.62 months VS 12.68±9.26 months (P<0.05) respectively. The grades of TCM symptoms, quality of life and KPS of treatment group before treatment are 15.59±3.77, 54.06±3.96, 64.71±6.24; and the grades after treatment are 10.53±5.57, 58.65±4.03, 69.41±4.29, there are significant difference (P<0.05) in all grades with a improving tendency, The grade of TCM symptoms, quality of life and KPS of control group before treatment are 16.11±3.99, 54.04±4.39, 64.44±5.11; and the grades after treatment are 19.61±7.79, 50.17±8.26, 60.00±9.70, the latter two figure group have significant difference (P<0.05), but the tendency is becoming worse. Conclusion: QUXIE capsule can prolong the media survival time, elevate the quality of life, and reduce the death rate, improve the TCM symptoms of the patients with advanced colorectal carcinoma, and the correctness of the discussion of TCM for tumor and the therapeutics and drug usage about collaterals was verified at the same time.
5. Cohort Study on Effect of Combined Treatment of Traditional Chinese Medicine and Western Medicine on the Relapse and Metastasis of 222 Patients with Stage II and III Colorectal Cancer after Radical Operation [4]. ABSTRACT Objective: To evaluate the effectiveness of comprehensive therapy of Traditional Chinese Medicine (TCM) in reducing the relapse and metastasis of stage II & III colorectal cancer based on conventional Western medicine therapy. Methods: A total of 222 patients diagnosed as stage II & III colorectal cancer from February 2000 to March 2006 were recruited from Xiyuan Hospital and the General Hospital of Beijing Military Area. They were followed up once every 3-6 months. Finally, 20 cases dropped out from the cohort. These remained 202 patients were all treated with routine Western medicine treatment (including R0 radical operation, or chemotherapy or/and radiotherapy according to NCCN (national comprehensive cancer network) clinical guideline. These patients were assigned to two groups by whether they were added with TCM comprehensive therapy (administered decoction orally according to syndrome differentiation combined with a kind of traditional patent drug over one year). Ninety-eight patients from Xiyuan Hospital were treated with Western medicine (WM) and TCM (combined group), and 104 patients from the General Hospital of Beijing Military Area were treated with WM alone (WM group), while demography data of the baseline were comparable, including operation times, age, sex, TNM staging, pathological types. They were followed up for one to five years. Up to now, there are 98, 98, 77, 64, and 47 patients with 1, 2, 3, 4, and 5 years of follow-ups in the combined group respectively, and 104, 104, 97, 81, and 55 patients within the WM group respectively. The results of 5-year follow- up of all patients will be available in 2011. Results: The relapse/metastasis rate of 1-, 2-, 3-, 4-, and 5-year were 0 (0/98), 2.04% (2/98), 11.69% (9/77), 14.06% (9/64), 21.28% (10/47) in the combined group and 4.80% (5/104), 16.35% (17/104), 21.65% (21/97), 25.93% (21/81), and 38.18% (21/55) in the WM group, respectively. Significant difference was found in the second year between the two groups (X2=12.117, P＝0.000). Median relapse/metastasis time was 26.5 months in the combined group whereas 16.0 months in the WM group. Conclusions: Combined therapy of TCM and WM may have the great clinical value and the potential for decreasing the relapse or metastasis rate of stage II and III colorectal cancer after conventional WM therapy.
6. At present, we are carrying out national eleventh five project “International multicenter pilot study on comprehensive therapy of Traditional Chinese Medicine raising the radical curative rate after colorectal cancer surgery”. Its license number is 2006BAI11B01 and the number registered in cohort study web is NCT00689364.We take this clinical trial with retrospective- prospective cohort study based on previous studies by international multi-center way. The participation of study included Norway national complimentary and alternative center and five grade III hospitals in Beijing. 450 patients who suffer from stage II, III colorectal cancer will be included in this study. The last result will display the conclusion with or without herbal medicine, on the basis of Conventional Western Medicine Therapy. We expect good result and let traditional Chinese medicine go into the world.
7. Currently, the Department of Oncology is awarded an operating grant to build the National Colorectal Cancer Specialty Centre and Clinical Program Leader for national Colorectal Cancer Care Alliance supported by State Administration of Traditional Chinese Medicine (SATCM) of the People’s Republic of China 11th Five-Year Plan, we are revising the diagnose and treatment standard of colorectal cancer. We believed that the objective study of colorectal cancer should be undertaken in several phases. If the study shows a positive result, a pragmatic randomized controlled study with prospective, multi-center and large sample design will be given continuously. The aim is to establish recommended programs suggested by CTTCM strategies under conventional Western medicine therapy (CWMT) for stage II & III colorectal cancer.
Acknowledgement: We would like to thank the director Liu Duanqi, oncology department in General hospital of Beijing military area, Dr. Zhao Aiguang and Dr. You Jie, Longhua hospital of Shanghai for their clinical support and help.
REFERENCE
1. May Lin Tao. Quality-of-Life Assessment in Pediatric Brain Tumor Patients and Survivors: Lessons Learned and Challenges to Face. Journal of Clinical Oncology. 2005, 23(24): 5424-5426.
2. Sheng Xiaoheng, Zhu Weirong , Zheng Lan. The clinical observation on enhancing the treatment effect and reducing the side and toxic effect in postoperative colorectal cancer patients treated by Shen-Mai injection and intraperitoneal chemotherapy (IPC). The 2nd international seminar paper assembles of integrated traditional and western medicine, and oncology of TCM. 2004:676-682.
3. Zhijun Tang, Shiping Tan, Shizhong Li et al. The clinical research on locus flower deintoxication anticancer decoction for the treatment of relapse and metastasis o f colorectal cancer. Journal of Chinese Medicine Forum. 2007; 5(51):33.
4. Yufei Yang, Jianzhong Ge, Yu Wu et al. Cohort Study on Effect of Combined Treatment of Traditional Chinese Medicine and Western Medicine on the Relapse and Metastasis of 222 Patients with Stage Ⅱ and Ⅲ Colorectal Cancer after Radical Operation. Chinese Journal of Integrated Traditional and Western Medicine. 2008; 14 (To be published).
* Correspondence to: Yufei Yang,
Department of Oncology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing (100091)
Email: yyf93@vip.sina.com