A randomized trial of chemotherapy and hormonal therapy in advanced breast cancer

We randomized 81 postmenopausal women with advanced breast cancer, whose tumors were rich in estrogen receptors or of unknown estrogen-receptor status, to receive either estrogen therapy alone or estrogen therapy combined with chemotherapy. An additional 31 patients, whose tumors were poor in estrogen receptors, were randomized to receive either chemotherapy alone or estrogen combined with chemotherapy. The median duration of follow-up was 87 months. In the receptor-rich group, the survival of the 21 patients receiving combined therapy was significantly longer than that of 19 patients receiving estrogen as initial therapy (followed by chemotherapy after failure or relapse). The median survivals were 72 and 29 months, respectively (P = 0.05 by the generalized Wilcoxon method). Among 41 patients with tumors of unknown receptor status, a survival advantage from combined therapy over chemotherapy was seen in the first two years and then disappeared. The survival in 31 patients with receptor-poor tumors was uniformly short regardless of the therapeutic method. We conclude that combined therapy offers a survival advantage in postmenopausal patients with receptor-rich tumors.     

A randomized trial of amifostine and carmustine-containing chemotherapy to assess lung-protective effects.

We conducted a randomized, double blind, placebo-controlled multi-institutional trial to assess the ability of amifostine to protect patients against acute lung injury associated with cyclophosphamide/cisplatin/carmustine (BCNU) (STAMP I), a BCNU-containing high dose chemotherapy regimen used with hematopoietic cell transplantation. Amifostine was administered in a dose of 740 mg/m(2) for 2 doses preceding administration of BCNU, the presumed pulmonary-toxic component of the regimen. The trial was stopped after 79 patients were randomized and a planned interim analysis demonstrated that it was unlikely that pulmonary cytoprotection would be detected with further accrual. We conclude that amifostine, used in the dose and schedule we tested, does not reduce the incidence of acute lung injury produced by STAMP I. Further, we suggest that amifostine use with BCNU in other contexts and with clinically achievable doses is unlikely to protect the lung from BCNU-associated acute injury.     

A randomized trial of induction chemotherapy plus high-dose radiation versus radiation alone in stage III non-small-cell lung cancer

BACKGROUND. For patients with locally or regionally advanced non-small-cell lung cancer radiation is the standard treatment, but survival remains poor. We therefore conducted a randomized trial to determine whether induction chemotherapy before irradiation improves survival. METHODS. All the patients had documented non-small-cell cancer of the lung with Stage III disease established by clinical or surgical staging. Eligibility requirements included excellent performance status, minimal weight loss, and visible disease on radiography. Patients randomly assigned to group 1 received cisplatin (100 mg per square meter of body-surface area given intravenously on days 1 and 29) and vinblastine (5 mg per square meter given intravenously on days 1, 8, 15, 22, and 29) and then began radiation therapy on day 50 (60 Gy over a 6-week period). Patients assigned to group 2 received the same radiation therapy but began it immediately and received no chemotherapy. RESULTS. The eligible patients in group 1 (n = 78) and group 2 (n = 77) were comparable in terms of age (median, 60 years), sex, performance status, histologic features, stage of disease, and completeness of radiation therapy. The median survival was greater for those in group 1-13.8 versus 9.7 months (P = 0.0066 by log-rank test). Rates of survival in group 1 were 55 percent after one year, 26 percent after two years, and 23 percent after three years, as compared with 40, 13, and 11 percent, respectively, in group 2. Those in group 1 had a higher incidence of serious infections requiring hospitalization (7 percent, vs. 3 percent in group 2) and severe weight loss (14 percent vs. 6 percent), but there were no treatment-related deaths. CONCLUSIONS. In patients with Stage III non-small-cell lung cancer, induction chemotherapy with cisplatin and vinblastine before radiation significantly improves median survival (by about four months) and doubles the number of long-term survivors, as compared with radiation therapy alone. Since three quarters of the patients still die within three years, however, further improvements in systemic and local therapy are needed.     

Hepatic arterial infusion of chemotherapy after resection of hepatic metastases from colorectal cancer

BACKGROUND: Two years after undergoing resection of liver metastases from colorectal cancer, about 65 percent of patients are alive and 25 percent are free of detectable disease. We tried to improve these outcomes by treating patients with hepatic arterial infusion of floxuridine plus systemic fluorouracil after liver resection. METHODS: We randomly assigned 156 patients at the time of resection of hepatic metastases from colorectal cancer to receive six cycles of hepatic arterial infusion with floxuridine and dexamethasone plus intravenous fluorouracil, with or without leucovorin, or six weeks of similar systemic therapy alone. Patients were stratified according to previous treatment and the number of liver metastases identified at operation. The study end points were overall survival, survival without recurrence of hepatic metastases, and survival without any metastases at two years. RESULTS: The actuarial rate of overall survival at two years was 86 percent in the group treated with local plus systemic chemotherapy and 72 percent in the group given systemic therapy alone (P=0.03). The median survival was 72.2 months in the combined-therapy group and 59.3 months in the monotherapy group, with a median follow-up of 62.7 months. After two years, the rates of survival free of hepatic recurrence were 90 percent in the monotherapy group and 60 percent in the monotherapy group (P<0.001), and the respective rates of progression-free survival were 57 percent and 42 percent (P=0.07). At two years, the risk ratio for death was 2.34 among patients treated with systemic therapy alone, as compared with patients who received combined therapy (95 percent confidence interval, 1.10 to 4.98; P=0.027), after adjustment for important variables. The rates of adverse effects of at least moderate severity were similar in the two groups, except for a higher frequency of diarrhea and hepatic effects in the combined-therapy group. CONCLUSIONS: For patients who undergo resection of liver metastases from colorectal cancer, postoperative treatment with a combination of hepatic arterial infusion of floxuridine and intravenous fluorouracil improves the outcome at two years.     

胰腺癌的区域动脉灌注化疗

对20例不可切除胰腺癌病人进行了区域动脉灌注化疗,采用经胃网膜右动脉置管至胃十二指肠动脉或胰十二指肠上动脉DDS泵植入术。经泵注入5—Fu 500mg、丝裂霉素C 8mg、卡铂100mg,每2周1次。29例中6例呈部分反应,占20.1％,15例呈稳定期,占51.7％,8例呈进展期,占28.2％,平均生存期9个月。结论,我们认为区域动脉灌注化疗治疗不可切除胰腺癌,具有改善病人生活质量、延长病人生存期的疗效。     

Exercise beliefs of breast cancer survivors before and after participation in a randomized controlled trial

The purpose of this study was to examine the exercise beliefs of breast cancer survivors before and after participation in a randomized trial. Prior to randomization, 52 breast cancer survivors completed exercise belief measures based on the theory of planned behavior. After the trial, participants assigned to the exercise group (n = 24) completed the belief measures again. Results show that there was significant variability in the expected benefits of exercise prerandomization, ranging from 40% for a reduced risk of breast cancer recurrence to 94% for an improved energy level. Moreover, attitudes toward exercise and perceptions of control were higher in the exercise group after the exercise program. The findings are discussed in terms of the veracity of the exercise beliefs held by breast cancer survivors as well as the aspects of the program that may have contributed to the positive changes in exercise beliefs.     

标准根治术与扩大根治术对于胰腺癌治疗的意义

目的 探讨标准根治术和扩大根治术对于治疗胰腺癌的临床疗效.方法 回顾性分析我院2010年7月至2012年10月收治的100例胰腺癌患者的临床资料,按治疗方法分为实验组58例(采用扩大根治术)和对照组42例(采用标准根治术),比较2组患者治疗效果.结果 实验组疼痛缓解率为89.55％,而对照组为66.67％,实验组并发症发生率为20.69％,对照组则高达40.48％,实验组患者切除率、疼痛缓解率以及生存率均明显高于对照组,具有统计学意义(P＜0.05).结论 胰腺癌确诊后应根据患者癌细胞转移范围,确定清除范围及根治术方案,使患者症状得到缓解.     

Histological differences between preoperative chemoradiotherapy and chemotherapy for rectal cancer: a clinicopathological study

Pathological studies on the different histological effects between neoadjuvant chemotherapy (NAC) and preoperative chemoradiation therapy (preoperative CRT) have not been performed. The purpose of this study is to elucidate the histological differences in tissue received from NAC and preoperative CRT for rectal cancer to evaluate whether a pathological assessment method used after CRT can be applied for NAC. One hundred and thirty‐eight patients were enrolled in this study; 88 patients underwent their operations after preoperative CRT or NAC, and 50 patients underwent surgery only. Residual tumor area was measured using morphometry software and we compared the stromal component of myofibroblasts, immune cells, and vasculature to elucidate the difference of therapeutic effect between them. The grade of reduction after preoperative CRT was more prominent than that seen in NAC. Also, ypT downstaging was more prominent in preoperative CRT than in NAC, and ypN downstaging was more frequent in NAC than in preoperative CRT. Preoperative CRT showed more marked myofibroblasts and fewer immune cells than did NAC, which indicates different effects on the cancer microenvironment. Our histological results suggest different effects between NAC and preoperative CRT on tumor tissue. The best assessment method available for a variable therapeutic protocol should be further investigated.     

Meta-analysis of FOLFIRINOX regimen as the first-line chemotherapy for locally advanced pancreatic cancer and borderline resectable pancreatic cancer

Clinical and Experimental Medicine - The study aimed to evaluate the effectiveness of the first-line chemotherapy FOLFIRINOX in treating pancreatic cancer. Pertinent studies were derived from the...     

Bevacizumab and cetuximab with conventional chemotherapy reduced pancreatic tumor weight in mouse pancreatic cancer xenografts

Pancreatic cancer remains the fourth leading cause of cancer-related death in the USA with a 5-year survival rate of 5 %. The effects of epidermal growth factor receptor and vascular endothelial growth factor A blockade with chemotherapy on pancreatic tumor growth were examined. Mice bearing human PANC-1 cell xenografts were divided into three groups: T-CR (gemcitabine, cisplatin, and 5-fluorouracil), T-TR (cetuximab, bevacizumab, gemcitabine, cisplatin, and 5-fluorouracil), and vehicle control (T). The therapies were administered via intraperitoneal injections every 4 days for seven cycles from 7 weeks after cancer cell implantation. Mice treated with T-TR had significant reductions in tumor weight as compared to the control group (p < 0.05). Although mice in the T-CR group experienced a significant reduction in body weight gain, serum albumin, and gastrocnemius muscle mass (p < 0.05), no such reductions were observed in the T-TR group. Mice treated with T-TR had slightly increased CD11c⁺ DC and CD49b⁺ NK cell levels in the spleen (p < 0.05) and significantly lower tumor VEGF expression (p < 0.05). Tumor carcinoembryonic antigen expression was significantly reduced in both treatment groups (p < 0.05). Thus, addition of bevacizumab and cetuximab to gemcitabine, cisplatin, and fluorouracil may represent an effective treatment option for pancreatic cancer that warrants further study.     

Routine assessment of psychosocial problems after cancer genetic counseling: results from a randomized controlled trial

Approximately 70% of counselees undergoing cancer genetic counseling and testing (CGCT) experience some degree of CGCT‐related psychosocial problems. We evaluated the efficacy of an intervention designed to increase detection and management of problems 4 weeks after completion of CGCT. In this randomized, controlled trial, 118 participants completed a CGCT‐related problem questionnaire prior to an – audiotaped – telephone session with their counselor 1 month after DNA‐test disclosure. For those randomized to the intervention group (n = 63), a summary of the questionnaire results was provided to the counselor prior to the telephone session. Primary outcomes were discussion of the problems, counselors' awareness of problems, and problem management. Secondary outcomes included self‐reported distress, cancer worries, CGCT‐related problems, and satisfaction. Counselors who received a summary of the questionnaire were more aware of counselees' problems in only one psychosocial domain (practical issues). No significant differences in the number of problems discussed, in problem management, or on any of the secondary outcomes were observed. The prevalence of problems was generally low. The telephone session, combined with feedback on psychosocial problems, has minimal impact. The low prevalence of psychosocial problems 1 month post‐CGCT recommends against its use as a routine extension of the CGCT procedure.     

miR-21 与 antimiR-21 在胰腺癌化疗中的作用简

胰腺癌发展恶化极快,加上非常容易产生化学治疗耐受,因此治疗颇为棘手。近年来发现这些均与microRNA（miR）-21高表达有关。antimiR-21是miR-21的抑制剂,含有与miR-21互补的核苷酸序列,与miR-21杂交使miR-21无功能从而达到治疗效果。文章阐述了miR-21在胰腺癌恶化中的作用机制及应对方案;在超声靶向破坏微泡技术（UTMD）的助推下荷药载体特异性大量进入胰腺癌细胞．实现靶向递送药物的目的,在简要综述的基础上对发展前景做一展望。     

Cimetidine for anastomotic ulcers after partial gastrectomy. A randomized controlled trial.

In a randomized double-blind multicenter trial, 15 outpatients with endoscopically proved anastomotic ulceration after Billroth I or Billroth II partial gastrectomy received cimetidine, 1 g daily over eight weeks, or a placebo. All patients also received antiacid. The ulcer healed completely in all seven cimetidine-treated patients and in one of the eight placebo-treated patients (P less than 0.01). Ulcers not healed during the double-blind phase of the trial were all subsequently healed on open cimetidine treatment. There was a trend toward improvement of daytime symptoms in favor of cimetidine (P = 0.06), and nighttime symptoms were significantly relieved during the initial four weeks of cimetidine treatment P = 0.02). We conclude that cimetidine, 1 g daily, promotes healing of anastomotic ulcers after partial gastrectomy.     

A randomized trial comparing combination electron-beam radiation and chemotherapy with topical therapy in the initial treatment of mycosis fungoides

Mycosis fungoides is a T-cell lymphoma that arises in the skin and progresses at highly variable rates. Nonradomized studies have suggested that early aggressive therapy may improve the prognosis in this usually fatal disease. We studied 103 patients with mycosis fungoides, who, after complete staging, were randomly assigned to receive either combination therapy, consisting of 3000 cGy of electron-beam radiation to the skin combined with parenteral chemotherapy with cyclophosphamide, doxorubicin, etoposide, and vincristine (n = 52) or sequential topical treatment (n = 51). The prognostic factors were well balanced in the two groups. Combined therapy produced considerable toxicity: 12 patients required hospitalization for fever and transient neutropenia, 5 had congestive heart failure, and 2 were later found to have acute nonlymphocytic leukemia. Patients receiving combined therapy had a significantly higher rate of complete response, documented by biopsy, than patients receiving conservative therapy (38 percent vs. 18 percent; P = 0.032). After a median follow-up of 75 months, however, there was no significant difference between the treatment groups in disease-free or overall survival. We conclude that early aggressive therapy with radiation and chemotherapy does not improve the prognosis for patients with mycosis fungoides as compared with conservative treatment beginning with sequential topical therapies.