Evaluation of Adjuvant Chemotherapy-Associated Steatosis (CAS) in Colorectal Cancer

Chemotherapy-associated steatosis is poorly understood in the context of colorectal cancer. In this study, Stage II–III colorectal cancer patients were retrospectively selected to evaluate the frequency of chemotherapy-associated steatosis and to determine whether patients on statins throughout adjuvant chemotherapy develop chemotherapy-associated steatosis at a lower frequency. Baseline and incident steatosis for up to one year from chemotherapy start date was assessed based on radiology. Of 269 patients, 76 (28.3%) had steatosis at baseline. Of the remaining 193 cases, patients receiving adjuvant chemotherapy (n = 135) had 1.57 (95% confidence interval [CI], 0.89 to 2.79) times the adjusted risk of developing steatosis compared to patients not receiving chemotherapy (n = 58). Among patients who underwent chemotherapy, those using statins for pre-existing hyperlipidemia (n = 37) had 0.71 (95% CI, 0.10 to 2.75) times the risk of developing steatosis compared to patients who were not prevalent users of statins (n = 98). Chemotherapeutic treatment of Stage II–III colorectal cancer appears to be consistent with a moderately increased risk of steatosis, although larger studies are necessary to assess the significance of this observation. Prospective trials should be considered to further explore the potential for protective use of statins in this curative patient population.     

Cooperative study of surgical adjuvant chemotherapy for colorectal cancer (third report): five-year results. Cooperative Study Group of Surgical Adjuvant Chemotherapy for Colorectal Cancer in Japan

A randomized controlled study was carried out by the envelope method with 491 institutions in participation across the country in order to find an optimal surgical adjuvant chemotherapy for curatively resected colorectal cancer. The schedules for drug administration were different in four districts: ACNU + Futraful (FT) group and FT alone group in the Hokkaido-Shikoku district; the same schedule groups plus untreated group in the Chubu-Kinki district; MMC+FT group, FT alone group in the Tohoku-Kanto district; and ADM+FT group and FT alone group in the Chugoku-Kyushu district. The numbers of patients admitted to this study were 2,450 cases with colon cancer and 2,456 cases met the evaluation criteria of this study. The 5-year survival rate on the whole did not differ from combination therapy to single drug therapy in either colon cancer or rectal cancer, but in Dukes C rectal cancer the five-year survival rate tended to be higher with the combination therapies. In n2 (+) or a2(s) rectal cancer in particular, combination therapies with MMC and FT and with ADM and FT achieved significantly higher five-year survival rate, and the rate of local recurrence was significantly lower with ADM+FT.     

美国乳腺与肠道外科辅助治疗研究组结直肠癌临床试验研究进展

美国乳腺与肠道外科辅助治疗研究组由美国国家癌症研究中心资助,主要进行大规模乳腺癌和结直肠癌临床试验.其临床试验为乳腺癌以及结直肠癌的治疗提供了重要的参考和指导价值.近5年来,NSABP结直肠癌临床试验就新的辅助化疗方案、靶向药物的作用以及直肠癌的新辅助治疗和辅助治疗的作用进行了深入的研究,取得了一些新的进展.     

美国乳腺与肠道外科辅助治疗研究组（NSABP）乳腺癌临床试验进展

美国乳腺与肠道外科辅助治疗研究组（National Surgical Adjuvant Breast and Bowel Project,简称NSABP）是一个进行大规模乳腺癌和结,直肠癌临床试验的合作团体,本文就NSABP有关乳腺癌的临床试验作一综述。     

The half century of clinical trials of the National Surgical Adjuvant Breast And Bowel Project

The supplanting of radical mastectomy by simple mastectomy and then by lumpectomy plus radiation, the use of adjuvant therapy to alter the natural course of breast and colorectal cancer, the use of tamoxifen for the prevention of breast cancer, and the dramatic improvement in survival demonstrated with the use of the monoclonal antibody trastuzumab in women with HER2-positive breast cancer are all the direct results of research that has been carried out over the past 50 years by the National Surgical Adjuvant Breast and Bowel Project (NSABP). This National Cancer Institute-supported clinical cooperative trials group based in Pittsburgh, PA, currently has 200 member institutions and 700 satellite centers located throughout the United States, Canada, Puerto Rico, and Ireland. The NSABP's mandate is to conduct large randomized phase III trials to evaluate therapies designed to improve the treatment and prevention of breast and colorectal cancer. Over the past half century, the NSABP has entered more than 150,000 patients and participants into clinical studies that have changed the treatment of colorectal cancer and have revolutionized the treatment and prevention of breast cancer.     

Final results of a randomized clinical trial of adjuvant intraportal chemotherapy for colorectal cancer: Intraportal Chemotherapy for Colorectal Cancer Group

The purpose of the present multi-center collaborative study was to elucidate the efficacy of intraportal chemotherapy with the combination of 5-FU and MMC for the prevention of liver recurrence after resection for colorectal cancer. A total of 125 patients with Stage II, III, and IV colorectal cancer were enrolled in this study between June 1993 and December 1995. Of them, 45 patients were randomized to a portal group: 10 mg/body of mitomycin one shot portal infusion, before and after 500 mg/m2 of 5-FU per 24 h for 7 days portal infusion followed by administration of oral 5-FU. Fifty-three patients were randomized to a control group: oral administration of 5-FU. Twelve patients suffered from temporary mild liver damage. One patient (2%) in the portal group and 6 patients (11%) in the control group developed liver metastases; there was not a significant difference between these two groups regarding development of liver metastases. There was also no significant difference by tumor stage between the portal and control groups regarding development of liver metastases. The 5-year survival rate and 5-year disease-free survival were 84.3% and 81.9%, respectively, in the portal group, and 70.7% and 72.4%, respectively, in the control group; the difference was not significant. Although there was not a significant difference between the portal and control groups regarding the prognosis in stage II, there was a significant difference between the portal and control groups regarding the 5-year disease free survival in stage III (81.1% vs 54.2%). These results suggest that intraportal chemotherapy is effective for stage III colorectal cancer.     

高龄大肠癌的外科治疗——附78例分析

通过对 78例高龄大肠癌的外科治疗 ,认为高龄大肠癌患者病程长 ,病情进展缓慢 ,预后好 ,就诊时间晚 ,误诊率高 ,并存病发生率高 ,手术是首选治疗方法 ,围手术期重要脏器检测处理是手术成功的关键。     

Establishment of histological criteria for high-risk node-negative breast carcinoma for a multi-institutional randomized clinical trial of adjuvant therapy. Japan National Surgical Adjuvant Study of Breast Cancer (NSAS-BC) Pathology Section

BACKGROUND: A multi-institutional randomized clinical trial of adjuvant therapy for patients with high-risk node-negative (n0) breast cancer has been undertaken in Japan. The pathology panel was organized in order to establish histological criteria to identify patient groups with higher rates of recurrence. METHODS: Initially, three pathologists independently judged the nuclear grade, composed of nuclear atypia and mitotic counts, of 100 n0 invasive ductal carcinomas, focusing on interobserver variation of the nuclear grade and its correlation with patient prognosis. These pathologists then gave consensus histological types and nuclear grades for 130 other n0 breast carcinomas and examined the prognostic significance of the grade. RESULTS: In the first study, nuclear grade 2-3 significantly identified a patient group with a rate of recurrence of 17-20% by any pathologists and the degree of agreement for the grade was fair. In the second study, the consensus type and nuclear grade identified a group (n = 66) with a 22% recurrence rate and another group (n = 64) with a 3.6% recurrence rate at 10 years. In 12 tumors, the resection-fixation interval of the tumor did not generate any significant difference in mitotic counts. CONCLUSIONS: The histological type and the nuclear grade clearly identified a higher-risk patient group with n0 breast carcinoma, and may be applied to the multi-institutional protocol study when the criteria have been well standardized by the pathologists.      

Tamoxifen and depression: more evidence from the National Surgical Adjuvant Breast and Bowel Project's Breast Cancer Prevention (P-1) Randomized Study.

BACKGROUND: Concerns have been raised that tamoxifen may be associated with depression. To investigate this question, we examined the psychological effects of tamoxifen treatment for breast cancer prevention on women at different levels of risk for clinical depression who were enrolled in the National Surgical Adjuvant Breast and Bowel Project's Breast Cancer Prevention (P-1) Study. METHODS: A total of 11 064 women were randomly assigned to receive for 5 years daily doses of 20 mg of tamoxifen or placebo in the P-1 study, a multicenter, double-blind, placebo-controlled chemoprevention trial. Each woman was prospectively assessed for depression risk on the basis of medical history items collected at the baseline examination and placed in a high-, medium-, or low-risk group. Every 6 months, for a total of 36 months, the participants were assessed for depressive symptoms by completing the Center for Epidemiological Studies-Depression (CES-D) questionnaire. Scores of 16 or higher were indicative of an episode of affective distress. Differences between the risk groups and treatment arms were analyzed by logistic regression. All statistical tests were two-sided. RESULTS: Women in the higher risk depression groups were more likely to score 16 or higher on the CES-D (percent follow-up examinations with a score of > or = 16: high-risk group = 35.7%, with 95% confidence interval [CI] = 32.5% to 38.9%; medium-risk group = 19.2%, with 95% CI = 18.1% to 20.3%; and low-risk group = 8.7%, with 95% CI = 8.3 to 9.1%) and to have these scores more frequently and for longer periods than women in the lower risk groups. Within each depression risk group, there was no difference in the proportion of women scoring 16 or higher by treatment assignment (tamoxifen versus placebo) (odds ratio = 0.98; 95% CI = 0.93 to 1.02). A post-hoc analysis indicated that the lack of a tamoxifen effect was not a result of differential missing data. CONCLUSIONS: Physicians need not be overly concerned that treatment with tamoxifen will increase the risk for or exacerbate existing depression in women. Nevertheless, physicians should continue to screen for and treat or refer potential cases of depression encountered in routine clinical practice.     

Adjuvant chemotherapy of colorectal cancer--results of prospective randomized trials

The group of research for colorectal cancer treatments-Kajitani-group (chief T. Kajitani) has carried out the co-operative study for the evaluation of adjuvant chemotherapy after curative resection of colorectal cancer. During the period 1975 and 1978, a series of 1,156 cases of cancer of colon and rectum were entered into the prospective randomized controlled study which consisted of three treatment programs. There included chemotherapy of 2 modes of regimen combining MMC with Tegaful and non adjuvant treatment as control. In colon cancer, adjuvant chemotherapy combining MMC with Tegaful was effective on the increasing of survival rates, especially significantly (p = 0.017) in the cases of Dukes B stage (85-88% vs 69.2% in survival rates of 8 year). In rectal cancer, systemic intravenous administration of MMC 4 mg, two times a week for immediately postoperative three weeks, combined with postoperatively prolonged oral administration of Tegaful 800 mg/day more than three months was also significantly effective, especially in the cases of Dukes C stage (52.3% vs 40% in survival rates of 8 year). However, the analysis of recurrence did not prove that the intra-operative local intra vessel administration of MMC 10 mg was useful for the prevention of liver metastasis in colon cancer or pelvic recurrence in rectal cancer respectively.     

Adjuvant chemotherapy in the treatment of colon cancer: randomized multicenter trial of the Italian National Intergroup of Adjuvant Chemotherapy in Colon Cancer (INTACC).

BACKGROUND: To determine whether the addition of leucovorin to the combination 5-fluorouracil plus levamisole prolongs disease-free survival and overall survival in patients with radically resected colon cancer (Dukes' B(2-3) and C). PATIENTS AND METHODS: Patients (1703) were accrued between March 1992 and February 1995 in a large-scale clinical trial within five Italian cooperative groups. After stratification for center, patients were randomized as follows: arm A, 5-fluorouracil [450 mg/m(2) intravenous (i.v.) bolus on days 1-5] and levamisole (150 mg orally for 3 days, every 14 days for 6 months) versus arm B, 6-S-leucovorin (100 mg/m(2) i.v. bolus on days 1-5) followed by 5-fluorouracil (370 mg/m(2) i.v. bolus on days 1-5), plus levamisole (as arm A), every 4 weeks for six cycles. RESULTS: After a median follow-up of 6.4 years no significant difference was seen for either disease-free survival (58% versus 60%, not significant) or 5-year overall survival (68% versus 71%, not significant), respectively. Gastrointestinal toxicity (World Health Organization grade 3/4) was more frequent in arm B (8% versus 18%, not significant). CONCLUSIONS: In this trial the schedules used showed no statistically significant differences in terms of disease-free survival or overall survival in the treatment of colorectal cancer.     

结直肠癌外科及辅助治疗新进展

随着循证医学的兴起,有关大肠癌治疗的多中心随机化研究在世界范围内广泛开展,为临床应用提供了可靠的证据。TME的疗效得到了进一步证实,强调在根治基础上保留植物神经功能的重要性。腹腔镜技术得到推广,腹腔镜大肠癌手术肿瘤学原则得到体现。进展期直肠癌术前辅助治疗安全性及疗效得到进一步肯定。辅助化疗方案得到进一步规范,分子靶向药物的临床应用给大肠癌治疗带来新的曙光。     

Adjuvant Treatment of Colorectal Cancer: Towards Tumor-specific Immunotherapies

Colorectal cancer is one of the leading causes of cancer-related mortality. After a series of clinical trials, the adjuvant 5-FU based chemotherapy has established a definitive role in the management of stage III colon cancer. The precise role for chemotherapy in stage II disease remains under investigation and less toxic treatment modalities like active specific immunotherapy have emerged as potentially attractive alternatives. It is most likely that the adjuvant treatment of colon cancer will move towards more tumor-specific immunotherapies using antibody- or vaccination-based strategies. Phase II/III clinical trials investigating these different modalities in colorectal cancer are reviewed.     

结直肠癌患者对含奥沙利铂辅助化疗的耐受性

 目的　对结直肠癌根治术后接受含奥沙利铂(LOHP) 辅助化疗患者的耐受性进行评价。 方法　对2001 年11 月～2008 年1 月在我院接受含LOHP 方案辅助化疗的250 例患者的临床资料进行 回顾性分析。包括三种化疗方案:LOHP 联合持续灌注5 氟尿嘧啶(52Fu) 和甲酰四氢叶酸钙(LV) 的两 周方案( FOL FOX4) 、LOHP 联合快速输注52Fu 和LV 的三周方案(LOHP/ Fu/ LV) 、LOHP 联合口服卡 培他滨的三周方案( XELOX) 。结果　三种方案LOHP 的相对剂量强度分别为99. 4 %、93. 3 %、 100. 5 %。中位完成治疗周期数分别为8 、6 、6 周期。不能耐受不良反应是患者提前终止治疗的主要原 因。恶心(88. 8 %) 、呕吐(45. 6 %) 和外周神经毒性(71. 2 %) 、中性粒细胞下降(38 %) 和血小板下降 (55. 6 %) 是最常见的不良反应。直肠癌患者与结肠癌相比,除了贫血的发生率稍高外,其他不良反应两 组之间无明显差别。结论　本组患者对含奥沙利铂方案辅助化疗的耐受性较西方人差。疗效是否有差 异还需等待生存的随访结果。     

直肠癌外科治疗进展

近几年随着直肠癌外科治疗的进展,直肠癌患者5年生存率明显提高,生活质量明显改善。全文对直肠癌外科治疗在保肛手术、腹腔镜技术、改善肛门功能方面的进展作一评述。     

Cooperative study of surgical adjuvant chemotherapy of colorectal carcinoma (second study): a preliminary report. Cooperative Study Group of Surgical Adjuvant Chemotherapy of Colorectal Cancer in Japan

In a prospectively randomized study, the effect of adjuvant chemotherapy with mitomycin C (MMC) and tegafur (FT) on survival and recurrence was analyzed in 2,477 evaluable patients with colon or rectal cancer who underwent macroscopically curative resection. Patients (1,256 with colon cancer, 1,221 with rectal cancer) were divided into the treatment group (group A) and the control group (surgical resection only, group B). In group A, chemotherapy consisted of intravenous administration of MMC (12 mg/m2 on operative day, followed by 6 mg/m2/2 months, 6 times) and oral administration of FT (800 mg/day for one year). No serious adverse effects were observed in the treatment group. There was no significant difference between group A and group B in three-year survival rate. The disease-free interval curve in group A of rectal cancer revealed significantly better results than group B (p = 0.044). There was no difference in the incidence of local recurrence at three years after operation between group A and group B. The incidence of metachronous liver metastases in group A of rectal cancer was significantly lower than in group B (p = 0.036).