The effect of postoperative radiotherapy on the feasibility of optimal dose adjuvant CMF chemotherapy in stage II breast carcinoma

The impact of a number of variables upon the effectiveness of adjuvant chemotherapy given to 87 patients with Stage II breast carcinoma was retrospectively analyzed. Adjuvant chemotherapy consisted of cyclophosphamide, methotrexate and 5-fluorouracil (CMF). Drugs were given in optimal doses (85% or more of the planned dose) to 17% of the patients; in intermediate doses (66 to 84% of the planned dose) to 50% of the patients; and in low doses (65% or less of the planned dose) to 33% of the patients. Myelosuppression was the main reason for giving intermediate or low doses. At a median follow-up of three years, 84% of all patients remain alive. Radiation therapy preceding chemotherapy was given to 70 % of the patients, concomitant irradiation and chemotherapy to 15 %, and 13 patients (15%) received chemotherapy only. Of the 14 patients who received optimal doses of CMF, 12 (86%) also received radiation therapy. Disease-free survival at three years is similar for irradiated and nonirradiated patients, but the latter have a higher incidence of local recurrence (5 % vs. 15 %), although the difference is not statistically significant. Delay in the initiation of chemotherapy, mostly because of the administration of postoperative irradiation, adversely affected the probability and duration of disease-free survival, particularly in premenopausal women in whom chemotherapy was started within more than 90 days of mastectomy. The administration of optimal doses of adjuvant chemotherapy should follow the primary treatment to the breast tumor as closely as possible. If radiation therapy is indicated as well, it should be delivered concomitantly with chemotherapy, given the feasibility of administering both modalities simultaneously, as demonstrated in this study.     

Feasibility of weekday-on/weekend-off oral UFT/Leucovorin schedule as postoperative adjuvant chemotherapy for colorectal cancer

Two phase III studies revealed an oral UFT/Leucovorin (LV) regimen, in which the drugs are taken for 28 consecutive days every 35 days, which proved to be equivalent to an infusional 5-fluorouracil/LV regimen for metastatic colorectal cancer (CRC). The weekday-on/weekend-off schedule for UFT, which is taken for 5 consecutive days followed by 2 drug-free days,has been reported to be safe and to have good feasibility. In the present study, we investigated the weekday-on/weekend-off schedule for UFT/LV in 54 patients with CRC. The median administration period was 8 months. Ten patients (19%) showed grade 2 or more severe adverse reactions. One of them had grade 3 diarrhea and anorexia. Grade 2 anemia was observed in 9 cases (19%) and grade 2 leucopenia was in 2 cases (4%). Myelotoxicity was mild. These results suggested that the adverse reactions in the weekday-on/weekend-off schedule for UFT/LV are less severe than the conventional UFT/LV schedule reported previously. Antitumor effects and survival benefits of the two schedules should be evaluated by a phase III study.     

Feasibility of a novel weekday-on/weekend-off oral UFT schedule as postoperative adjuvant chemotherapy for colorectal cancer

Purpose: When oral anticancer agents are used for adjuvant chemotherapy of colorectal cancer, compliance and feasibility become issues because of the long treatment time. Appropriate studies of these issues are lacking. We investigated compliance and feasibility during a weekday-on/weekend-off schedule of oral UFT (uracil-tegafur) over a period of 1 year administered as adjuvant chemotherapy to patients with colorectal cancer. Patients and methods: A UFT dose of 600 mg/day was prescribed according to a weekday-on/weekend-off schedule to 87 patients after potentially curative resection. Compliance was investigated in three ways: physician interview, patient self-report, and chemical analysis of urine. The results were compared with the dose prescribed. Feasibility was evaluated on the basis of two indices: relative performance (RP), which was the ratio of the actual total dose taken to the total dose planned, and individual dose intensity (IDI), which was the ratio of the actual dose taken to the dose planned during a given period. Results: The compliance assessed by physician interview and by patient self-report conformed well with the prescribed dose, the rate of agreement among the three compliance measures being more than 94%. Chemical analysis of urine in 38 of the patients revealed that they were actually taking the drug. The RP was 0.72, and the IDI was 0.8. Conclusion: From these results, the feasibility of the weekday-on/weekend-off schedule was judged to be good. It is suggested that the feasibility would be even better if the dose of UFT was set according to body surface area. Received: 10 November 1999 / Accepted: 5 April 2000     

Clinical effect of postoperative adjuvant chemotherapy for advanced colorectal cancer--comparisons of between tegafur (FT) and UFT

A randomized controlled study was conducted on a FT 600 mg/day daily oral administration group and a UFT 400 mg/day daily oral administration group as an adjuvant chemotherapy after curative operation for colorectal cancer patients with injection of Mitomycin 30 mg (20 mg during operation and 10 mg on the day following), and the results were examined. FT and UFT were administered orally for one year from the 3rd week after operation. The 5-year survival rate was slightly higher in the UFT administration group. Five-year survival was 82.7% for colon cancer and 82.1% for rectal cancer in the UFT administration group, against 72.6% and 72.0 % in the FT administration group. The same trend was observed when the survival rate was studied by various factors such as the size of tumor, depth of cancer invasion of the wall, histological type, lymph node metastasis, vascular invasion and the degree of progression. There was no difference between both groups in the patterns and times of recognition of the recurrences and in the appearance rate of side effects. The results suggest that UFT 400 mg/day is equal to or better than FT 600 mg/day in therapeutic effect for colorectal cancer patients, although the UFT dose is only 2/3rd the FT dose.     

Optimal dosage of UFT in a weekday-on/weekend-off schedule as a postoperative adjuvant chemotherapy for colorectal cancer

In evaluations of adjuvant chemotherapy with oral anticancer agents, compliance in taking the drug as prescribed (compliance), adverse reactions, and feasibility are important factors in setting the dose. A weekday-on/weekend-off schedule, in which 600 mg/day of UFT was taken for 5 consecutive days and not taken on the following 2 days, was carried out as a postoperative adjuvant chemotherapy for one year in 87 patients with colorectal cancer who had undergone potentially curative resection. The prescribed dose and the dose of ingestion confirmed by physician interview were both highly consistent with the dose of ingestion according to the patients' self reports, with consistency rates of more than 94% for both. Relative performance (RP) yielded a value of 0.72, and individual dose intensity (IDI) yielded 0.8 on average. Female gender, low body weight, and low body surface area were factors that negatively affected feasibility. None of the adverse reactions was serious. Based on the feasibility and adverse reactions, the dosage of UFT should be set according to the body surface area at 375-425 mg/m2/day. When this schedule is used as one arm of a controlled study, it is suggested that the dose should be decided with 400 mg/m2 as a guideline.     

高危早期子宫内膜癌术后辅助放疗与化疗的临床对比研究

目的探讨高危早期子宫内膜癌术后辅助放疗与化疗的临床效果。方法选取2011年11月至2013年11月间新疆维吾尔自治区人民医院收治的接受手术治疗的90例高危早期子宫内膜癌患者,采用随机数表法分为放疗组与化疗组,每组45例,比较两组患者的近期不良反应及随访3年的生存率、局部复发率和远处转移率。结果与放疗组比较,化疗组骨髓抑制、肠道反应、泌尿系统反应及皮肤反应发生率均较低,差异均有统计学意义(均P<0.05)。放疗组患者的3年生存率、局部复发率和远处转移率分别为66.7%、20.0%和28.9%,化疗组生存率、局部复发率和远处转移率分别为86.7%、8.9%和13.3%,化疗组随访3年生存率较高,局部复发率及远处转移率较低,差异均有统计学意义(均P<0.05)。结论对接受手术治疗的高危早期子宫内膜癌患者术后给予化疗的效果明显优于放疗,局部复发率及远处转移率较低,生存率较高,不良反应较轻。     

Adriamycin-methotrexate high dose versus adriamycin-methotrexate moderate dose as adjuvant chemotherapy for osteosarcoma of the extremities: a randomized study

Adjuvant chemotherapy comprising Adriamycin (ADM) and Methotrexate (MTX) with Citrovorum Factor (CF) was administered on a randomization basis to 2 groups of patients with osteosarcoma after surgical ablation of the primary tumor. One group received high dose MTX (regimen I) and the other moderate dose MTX (regimen II). In both groups a short period of heparin treatment was also administered to prevent neoplastic emboli during surgery. All patients were free of metastasis at the beginning of therapy. The efficacy of therapy was determined by recording the percentage of continuously disease-free patients. This was compared to the disease-free survival in 132 patients previously treated with other ADM or ADM-MTX regimens and to a group of 39 patients treated during this period with amputation only. The latter did not receive adjuvant chemotherapy for a variety of reasons and are equated to a concurrent control group. Over the ensuing 27–66 months, 31 of 56 patients (55%) treated with regimen I and 25 of 50 (50%) treated with regimen II were disease-free. The overall disease-free survival in both regimens was 53%. This is similar to the 132 patients treated with previous adjuvant chemotherapy protocols (45–50%). However, the percentage of continuously disease-free patients treated with adjuvant chemotherapy was significantly better than the 39 patients (12%) treated contemporaneously with surgery only (P < 0.0005). Survival in the latter is similar to that of historical control patients. These results do not suggest any change in the natural history of osteosarcoma and reveal benefits which may accrue with adjuvant chemotherapy. These results also demonstrate that in adjuvant treatment of osteosarcoma performed with ADM and MTX the high and the moderate doses of MTX are equally efficacious.     

Study on the intensity of MMC and UFT in postoperative adjuvant chemotherapy for gastric cancer--study report of JFMTC Study No. 10

The purpose of this study was to investigate the correlation between efficacy and dose intensity of postoperative adjuvant chemotherapy with MMC and UFT. A total of 1,410 patients from 180 institutions were allocated into a low-dose group and a high-dose group. The patients in the low-dose group received MMC at 8 mg/m2 on the day of surgery and 3 capsules of UFT (300 mg in tegafur) daily for 6 months. The patients in the high-dose group received MMC at 8 mg/m2 on the day of surgery, and in weeks 4, 10, 16, and 22 after surgery and 6 capsules of UFT (600 mg in tegafur) daily for 6 months. The patients in the high-dose group tended to exhibit higher survival rates than those in the low-dose group, although the difference was not significant. For the n(+)ps(-) patients, however, the survival rates were significantly higher in the high-dose group (p = 0.043). The recurrence-free rates showed a similar tendency. The incidence rates of adverse events were significantly higher in the high-dose group than in the low-dose group. Compliance was poorer in the high-dose group. Although the number of adverse events increases, a better prognosis can be expected with a high dose. These results confirmed a dose-dependency in adjuvant chemotherapy with MMC and UFT.     

胃肠肿瘤术后辅助化疗患者对口服营养补充体验的质性研究

目的 在口服营养补充广泛应用在胃肠道恶性肿瘤患者的营养治疗的背景下,了解胃肠肿瘤术后辅助化疗患者服 用口服营养粉后的认识和感受,为临床指导提供依据,进而提高患者依从性,确保营养治疗效果。方法 采用目的抽样法,以分层目的性选样策略,选取14名于2017年11月至2018年4月在南京市某三甲医院接受口服营养补充的胃肠肿瘤术后 辅助化疗患者,对患者进行半结构式深入调研,运用Nvivo11软件,对调研结果进行分析和整理。结果 分析提炼出3个主题, 患者对口服营养补充的态度认知、服用问题反馈和健康信息关注情况。大部分患者对口服营养补充认识不足,仅有21% 的 患者在服用口服营养补充后对其持肯定态度;有合并症的患者有特殊需求、不明白服用方法和出现不适反应为患者服用问 题反馈;半数患者不主动关注健康信息。主动关注的患者主要通过互联网和咨询医务人员。结论 患者对口服营养补充的体 验具有多面性,反映的问题也不容乐观。应采取医护一体化合作模式,改进健康教育流程,在院和延续护理中重视症状管理, 推广多口味、多配方的营养粉和加强对网络健康信息的监管。以改善患者临床结局,进而提高生活质量。     

Molecular classification of breast cancer: implications for selection of adjuvant chemotherapy

Adjuvant chemotherapy improves survival of patients with stage I-III breast cancer but it is being increasingly recognized that the benefit is not equal for all patients. Molecular characteristics of the cancer affect sensitivity to chemotherapy. In general, estrogen-receptor-negative disease is more sensitive to chemotherapy than estrogren-receptor-positive disease. Large-scale genomic analyses of breast cancer suggest that further molecular subsets may exist within the categories defined by hormone receptor status. It is hoped that the new molecular classification schemes might improve patient selection for therapy. Before any new molecular classification (or predictive test) is adopted for routine clinical use, however, several criteria need to be met. There must be an agreed and reproducible method by which to assign molecular class to a new case. Cancers that belong to different molecular classes must show differences in disease outcome and treatment efficacy that affect management and treatment selection. Also desirable are results from prospective clinical trials that demonstrate improved patient outcome when the new test is used in decision-making, compared with the current standard of care. This Review describes the current limitations and future promises of gene-expression-based molecular classification of breast cancer and how it might impact on selection of adjuvant therapy for individual patients.     

Prognostic factors in stage I non-seminomatous germ-cell testicular tumors managed by orchiectomy and surveillance: implications for adjuvant chemotherapy

Between February 1979 and March 1985, 126 patients with clinical stage I non-seminomatous germ-cell testicular tumors were entered into a surveillance study after orchiectomy. Of this group, 36 (28%) have relapsed. The prognostic significance of 13 clinical, histopathologic, and biochemical factors has been analyzed. Vascular invasion and lymphatic invasion (LI) within the primary tumor, histology, and involvement of the epididymis and rete testis were significantly associated with an increased risk of relapse. However, multiple regression analysis showed that only histology and LI were significant, independent prognostic factors. These findings provide the basis for the consideration of adjuvant chemotherapy for patients with apparent clinical stage I testicular non-seminoma who are at high risk of harboring occult metastases.     

Meta-analysis of five studies on tegafur plus uracil (UFT) as post-operative adjuvant chemotherapy for breast cancer

Meta-analysis of 5 studies on postoperative breast cancer cases (2 studies on surgery alone vs. tegafur plus uracil (UFT) and 3 studies on tamoxifen (TAM) alone vs. TAM + UFT) were carried out to evaluate the anticancer drug UFT in oral postoperative adjuvant chemotherapy. Of the 1973 patients enrolled, 1898 were eligible and 75 were excluded (exclusion rate 3.8%). There was no bias in major background factors in either the UFT-treated (965) or non-UFT-treated (933) groups. The reduction in the odds of death and the odds of recurrence were 17 +/- 17% (p = 0.33) and 21 +/- 11% (p = 0.060), respectively. Multivariate analysis using Cox's proportional hazards model emphasized the effectiveness of UFT treatment for suppression of recurrence compared with non-treatment with UFT (p = 0.038). Suppression of recurrence was remarkable in the group treated with UFT for 2 years. (the reduction in the odds of recurrence: 23 +/- 11%, p = 0.048) Stratified analysis was applied concerning recurrence, and improved results were obtained in premenopausal cases (the reduction in the odds of recurrence: 33 +/- 11%, p = 0.019). These results suggested that UFT treatment for 2 years was effective as postoperative adjuvant chemotherapy for stage I - IIIA breast cancer for the prolongation of the recurrence-free survival period.     

老年乳腺癌术后多西紫杉醇联合环磷酰胺辅助化疗的毒副作用研究

Objective: The aim of this study was to investigate the side effects of docetaxel with cyclophosphamide as postoperative adjuvant chemotherapy for elderly breast cancer patients. Methods: Thirty-six operable elderly breast cancer patients at intermediate risk based on the St Gallen risk classification underwent modified radical mastectomy and then were given four cycles of TC regimen (docetaxel 75 mg/m2 i.v. on day 1; cyclophosphamide 600 mg/m2 i.v. on day 1; every 21 days ). Primary prophylaxis granulocyte...     

Late effects of adjuvant chemotherapy and postoperative radiotherapy on quality of life among breast cancer patients

Late effects of adjuvant treatment on perceived health and quality of life were assessed through a questionnaire mailed to 448 premenopausal and postmenopausal breast cancer patients, free from recurrence 2–10 years after primary therapy. The patients had been randomised to postoperative radiotherapy or adjuvant chemotherapy as adjuncts to primary surgery. The differences between the two treatments were generally small. However, the radiotherapy patients had significantly greater problems with decreased stamina, symptoms related to the operation scar and anxiety. The chemotherapy patients had significantly more problems with smell aversion. Activity level inside and outside the home, anxiousness and depressive symptoms were similar in both groups. The chemotherapy patients scored their overall quality of life higher than the radiotherapy patients.     

Preoperative chemotherapy for osteogenic sarcoma: selection of postoperative adjuvant chemotherapy based on the response of the primary tumor to preoperative chemotherapy

Since June 1978, 57 patients with primary osteogenic sarcoma of an extremity were treated with high-dose methotrexate (HDMTX) and citrovorum factor rescue (CFR), Adriamycin, and the combination of bleomycin, cyclophosphamide and dactinomycin (BCD) given for 4-16 weeks prior to definitive surgery. Histologic examination of the resected primary tumor determined the effect of preoperative chemotherapy with many primary tumors showing greater than 90% tumor necrosis attributable to preoperative chemotherapy. All patients having this favorable effect of chemotherapy on the primary tumor were continued on the same chemotherapy regimen postoperatively (regimen B). However, in those patients not having a good effect of preoperative chemotherapy on the primary tumor, HDMTX with CFR was subsequently deleted from their postoperative chemotherapy and they were placed on a regimen containing cisplatinum at the dose of 120mg/M2 with mannitol diuresis combined with Adriamycin in addition to BCD (regimen A). In the current study, 35 of the 57 patients did not demonstrate a good effect of chemotherapy on the primary tumor and were assigned to regimen A postoperatively. Of these 35 patients, 32 (91%) have remained continuously free of recurrent or metastatic disease from 6-34 months following the start of therapy. Among the 22 remaining patients having a good histologic response and treated with regimen B postoperatively, there has been only one relapse in a patient who had a local recurrence in the area of an inadequately resected primary tumor three months after the cessation of chemotherapy. Thus, 53 of 57 patients (93%) are continuously with no evidence of recurrent or metastatic disease from 6-35 months (median, 20 months) from the start of treatment. This study demonstrates the value of thorough histologic examination in predicting survival in responding patients and in helping identify patients whose disease-free survival rate can be substantially increased if they are given alternative postoperative adjuvant chemotherapy after failing to have a good response to preoperative chemotherapy. This individualized chemotherapeutic strategy has yielded the highest disease-free survival rate reported to date for osteogenic sarcoma.     

Role of postoperative adjuvant chemotherapy with gemcitabine for pancreatic cancer: feasibility and anti-tumor effect

BACKGROUND: The feasibility and anti-tumor activity of gemcitabine in postoperative adjuvant chemotherapy were evaluated retrospectively. PATIENTS AND METHODS: Sixteen patients with advanced pancreatic cancer, who had a pancreatic resection with curative intent over the three years up to February 2003, were enrolled in this study. Aggressive surgery with dissection of para-aortic nodes and nerves around the superior mesenteric and celiac artery was carried out. After the operation, all patients have been given biweekly administration of 1,000 mg/m2 gemcitabine for more than 12 courses. RESULTS: The chemotherapy was well tolerated with only mild symptomatic and hematologic toxicities. Grade 3 adverse effects were observed in only 3 patients (19%); nausea and vomiting in 1 patient and leucocytopenia in 2 patients. The disease-specific cumulative survival rates were 81% at 1 year and 47% at 2 years, with a median survival of 20.4 months. The median disease-free interval was 16.8 months in all patients. CONCLUSIONS: Adjuvant systemic chemotherapy utilizing gemcitabine was feasible with acceptable adverse effects. Gemcitabine is a promising agent for the treatment of resectable advanced pancreatic cancer, and a randomized control trial is warranted for gemcitabine-based chemotherapy.     

A randomized phase III trial comparing S-1 versus UFT as adjuvant chemotherapy for stage II/III rectal cancer (JFMC35-C1: ACTS-RC)

BackgroundsPreventing distant recurrence and achieving local control are important challenges in rectal cancer treatment, and use of adjuvant chemotherapy has been studied. However, no phase III study comparing adjuvant chemotherapy regimens for rectal cancer has demonstrated superiority of a specific regimen. We therefore conducted a phase III study to evaluate the superiority of S-1 to tegafur–uracil (UFT), a standard adjuvant chemotherapy regimen for curatively resected stage II/III rectal cancer in Japan, in the adjuvant setting for rectal cancer.Patients and methodsThe ACTS-RC trial was an open-label, randomized, phase III superiority trial conducted at 222 sites in Japan. Patients aged 20–80 with stage II/III rectal cancer undergoing curative surgery without preoperative therapy were randomly assigned to receive UFT (500–600 mg/day on days 1–5, followed by 2 days rest) or S-1 (80–120 mg/day on days 1–28, followed by 14 days rest) for 1 year. The primary end point was relapse-free survival (RFS), and the secondary end points were overall survival and adverse events.ResultsIn total, 961 patients were enrolled from April 2006 to March 2009. The primary analysis was conducted in 480 assigned to receive UFT and 479 assigned to receive S-1. Five-year RFS was 61.7% [95% confidence interval (CI) 57.1% to 65.9%] for UFT and 66.4% (95% CI 61.9% to 70.5%) for S-1 [P = 0.0165, hazard ratio (HR): 0.77, 95% CI 0.63–0.96]. Five-year survival was 80.2% (95% CI 76.3% to 83.5%) for UFT and 82.0% (95% CI 78.3% to 85.2%) for S-1. The main grade 3 or higher adverse events were increased alanine aminotransferase and diarrhea (each 2.3%) in the UFT arm and anorexia, diarrhea (each 2.6%), and fatigue (2.1%) in the S-1 arm.ConclusionOne-year S-1 treatment is superior to UFT with respect to RFS and has therefore become a standard adjuvant chemotherapy regimen for stage II/III rectal cancer following curative resection.