Feasibility of dose-intensive continuous 5-fluorouracil, doxorubicin, and cyclophosphamide as adjuvant therapy for breast cancer

BACKGROUND: Several studies support the belief that the efficacy of adjuvant chemotherapy in breast cancer is related to the dose intensity of the chemotherapy used (expressed in milligrams per square meter per week). Retrospective analyses indicate that the actual delivered dose intensity may correlate more strongly with efficacy than the intended dose delivery. METHODS: A doxorubicin-based adjuvant regimen was studied for breast cancer. It was modeled on the Southwest Oncology Group's regimen of cyclophosphamide, methotrexate, and 5-fluorouracil in that daily oral cyclophosphamide and weekly intravenous 5-fluorouracil were used, but weekly doxorubicin was substituted for methotrexate and administered in both the adjuvant and neoadjuvant setting to 29 patients. RESULTS: The actual dose delivery was 1.21-1.24-fold that calculated for the delivered dose in the two other adjuvant regimens using the same three drugs (5-fluorouracil, doxorubicin, and cyclophosphamide) for which this could be determined. This regimen was tolerated well. Toxicity was minimal and consisted largely of expected neutropenia. CONCLUSIONS: Whether improved dose intensity can be increased further with the use of growth factors or actually confers improved outcomes awaits the results of larger future trials.     

Lung cancer after radiation therapy for breast cancer

BACKGROUND: Radiation, including radiation therapy (RT) for a variety of conditions, is known to be a lung carcinogen. METHODS: Data from the Surveillance, Epidemiology, and End Results program of the National Cancer Institute for 1973-1986 were utilized to investigate whether RT for breast cancer affects the risk of subsequent lung cancer. The relative risk was calculated by comparing the incidence rate in patients with irradiated breast cancer with that in those with nonirradiated breast cancer. RESULTS: It was found that the risk of lung cancer overall was increased in women who underwent irradiation compared with those who were not irradiated 10 years after the initial breast cancer diagnosis with a relative risk of 2.0 (95% confidence interval, 1.0-4.3). In addition, the risk of lung cancer was in the ipsilateral lung compared with the contralateral lung for irradiated women. This increase was observed after 10 years for lung cancer overall and for the three major histologic subgroups (small cell, squamous cell, and adenocarcinoma). Specific information on RT doses and treatment plans and cigarette smoking were not available. CONCLUSIONS: It was concluded that RT for breast cancer may increase the risk of lung cancer after a latency period of 10 years.     

Feasibility of adjuvant chemotherapy for breast cancer patients

The prevalence and natural history of severe proteinuria in mild to moderate hypertension are not completely defined. We screened 1635 men with a history of hypertension and randomized 1292 with untreated diastolic blood pressure (DBP) 95-109 mmHg to single-drug treatment with either hydrochlorothiazide, atenolol, captopril, clonidine, diltiazem-SR, prazosin, or placebo in a double-blind prospective trial. Twenty-seven of 1635 patients (1.7%) satisfying clinical criteria for primary hypertension were found to have developed proteinuria > 1000 mg/24 hours and were removed from the study. Follow-up data were obtained on 19 of these 27 patients. One patient was found to have focal segmental sclerosis and progressed to end-stage renal disease. Three other patients developed severe (serum creatinine > 3.5 mg/dl) chronic renal failure (one with diabetic nephropathy), one progressed from serum creatinine 1.4 to 2.2 mg/dl, but 14 of the 19 remained with stable serum creatinine < 2.0 mg/dl on follow-up for 6-9 years. Data were available for 1076 of 1155 (93%) treated study patients at end titration, 522/600 (87%) at one year and 322/444 (73%) at two years. There were significant associations for proteinuria with obesity and higher systolic blood pressure. There was a trend toward significant difference in mean 24-hour protein excretion rates at baseline between black (127 mg) and white (139 mg) patients (p = 0.07). There were no statistically significant changes in urinary protein excretion/24 hours between or within the different treatment groups (including placebo). Eighteen patients were removed from the study during the active treatment phase for proteinuria > 1000 mg/24 hours: hydrochlorothiazide 4, placebo 3, diltiazem 3, prazosin 3, atenolol 2, clonidine 2, and captopril 1. We conclude: (1) the prevalence of severe (> 1 g/24 hours) proteinuria in the hypertensive population is significant but does not necessarily imply a poor prognosis; (2) mean 24-hour urinary protein excretion rates did not vary in response to the different classes of antihypertensive drugs; and (3) there was no drug-specific increase in proteinuria detected in this study.     

Short-term effects of telephone therapy for breast cancer patients.

The authors report the short-term effects of a clinical trial testing 2 telephone therapies for breast cancer patients. Women (N = 222) with breast cancer were recruited and randomly assigned to cancer education, emotional expression, or standard care. Oncology nurses conducted 6 individual 30-min-therapy phone sessions. Women in the cancer education condition reported greater perceived control than women in the standard care condition. No treatment effects were obtained for mood or quality of life. These are the 1st data from a large-scale study testing telephone therapy, and they suggest that such therapies may be ineffective. Explanations for the results include therapy type and delivery, participant characteristics, short- versus long-term results, therapy content, and whether therapy is necessary for breast cancer patients. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The role of adjuvant radiation therapy in the treatment of colorectal cancer

The hypercatabolic response to trauma, extensive surgery and sepsis is characterized by an increased metabolic rate, severe muscle wasting and a negative nitrogen balance. This process of 'autocannibalism' may be in part a consequence of a disordered growth hormone (GH)/insulin-like growth factor (IGF) axis. In this chapter the normal physiology of the GH/IGF axis is first briefly reviewed. This is followed by a discussion of the changes that accompany fasting and catabolic illness, the effects of IGF-1 administration in health and disease and a comparison of the effects of IGF-1, GH and insulin on catabolism. Although initial investigations of IGF-1 administration in animals and human volunteers have often been encouraging, studies in catabolic patients have so far proved disappointing. Combined treatment with GH, IGF-1 (and insulin) or with IGF-1 and its major binding protein, may prove more effective, especially when used in conjunction with nutritional supplements such as glutamine.     

The current status of adjuvant hormonal therapy combined with radiation therapy for localised prostate cancer

The limbic system comprises the hippocampal formation, fornix, mamillary bodies, thalamus, and other integrated structures. It is involved in complex functions including memory and emotion and in diseases such as temporal lobe epilepsy. Volume measurements of the amygdala and hippocampus have been used reliably to study patients with temporal lobe epilepsy but have not extended to other limbic structures. We performed volume measurements of hippocampus, amygdala, fornix and mamillary bodies in healthy individuals. Measurements of the amygdala, hippocampus, fornix and mamillary bodies revealed significant differences in volume between right and left sides (P < 0.001). The intraclass coefficient of variation for measurements was high for all structures except the mamillary bodies. Qualitative image assessment of the same structures revealed no asymmetries between the hemispheres. This technique can be applied to the study of disorders affecting the limbic system.     

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 classi.cation 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 colony stimulating factor (G-CSF) 200μg i.h. was administered on day 4-6. Results: The main side effect was neutropenia. Grade 3 neutropenia developed in 36.1% and G4 in 19.4%, respectively. Most of the other side effects were G1-2. Dose reduction occurred in 11.1% patients. The completion rate of chemotherapy was 100%. Conclusion:Docetaxel with cyclophosphamide as postoperative adjuvant chemotherapy regimen with G-CSF primary prophylaxis is tolerable for elderly patients in general good condition.     

Immunology and adjuvant chemoimmunotherapy of breast cancer

Antibody against a breast carcinoma antigen was present in patients with breast carcinoma and other cancer more often (P less than .05) than in normal women. The incidence of antibody in women with breast carcinoma correlated with the presence or absence of gross tumor, and the titer of antibody paralleled the clinical course. These results suggest importance of a host-immune response to breast carcinoma. Fifty-seven patients with stage II carcinoma of the breast were entered into a prospective randomized adjuvant chemoimmunotherapy program of cyclophosphamide, methotrexate, and fluorouracil, and BCG vaccine +/- an irradiated allogeneic tumor cell vaccine. After 24 months of study, metastases occurred in two patients (3.5%) and a new primary carcinoma developed in the contralateral breast in two others, for an overall treatment failure rate of 7%. Adjuvant chemoimmunotherapy can delay early recurrence. Long-term follow-up is needed to assess the significance of these results.     

The effects of a low-fat dietary intervention and tamoxifen adjuvant therapy on the serum estrogen and sex hormone-binding globulin concentrations of postmenopausal breast cancer patients

The purpose of the study was to determine the effect of a low-fat dietary intervention, with or without concomitant tamoxifen adjuvant therapy, on serum estrogen and sex hormone-binding globulin (SHBG) levels in postmenopausal patients with resected breast cancer. Ninety-three patients were randomized to either reduce their fat intake to 15-20% of total calories, or to a dietary control group. Serum estradiol, estrone, estrone sulfate, and SHBG concentrations were assayed at baseline, and at 6, 12, and 18 months thereafter. In 19% of patients, the preintervention serum estradiol levels were below the sensitivity of the assay (5 pg/ml). Tamoxifen had no significant effect on serum estrogen levels, but produced an elevation in SHBG. Patients with reliably quantifiable preintervention estradiol concentrations (> or = 10 pg/ml) showed a significant reduction in serum estradiol after 6 months on the low-fat diet (average, 20%; p < 0.005); this was sustained over the 18 month study period. Serum SHBG levels were increased by tamoxifen therapy, but were reduced significantly (p = 0.01) after 12 months on the low-fat diet in patients not receiving tamoxifen. No changes in serum estrone or estrone sulfate resulted from the dietary intervention. While the low-fat diet produced significant weight loss, patients treated with tamoxifen without dietary intervention showed a gain in body weight. These weight changes produced disruptions in the normal positive correlation between body weight and serum estrone sulfate, and the negative correlation with SHBG concentration.     

A cooperative randomized controlled study of adjuvant chemoendocrine therapy for breast cancer in Japan

Social competence in subjects at risk for schizophrenia and affective disorder and in normal-comparison subjects was examined in childhood and adolescence. Based on interviews with the parents of the subjects and with the children and adolescents themselves, subjects at risk for schizophrenia had poorer overall social competence than subjects at risk for affective disorder and comparison subjects in early adolescence and adolescence but not in childhood. In analyses of specific aspects of social competence, the adolescents at risk for schizophrenia had significantly poorer peer relationships and decreased hobbies/interests than the adolescents at risk for affective disorder and the normal-comparison adolescents. With respect to school adjustment, however, the two groups of adolescent offspring of parents with psychiatric disorders had significantly poorer adjustment than the comparison adolescents but did not differ from each other on this measure. These results suggest that various aspects of poor social competence may precede the onset of schizophrenia and play an important role in its development.     

Metabolic response to radiation therapy in patients with cancer

The effect of radiation therapy on substrate metabolism was evaluated in five patients with head and neck or lung cancer. Stable isotope tracer methodology was used to determine urea, amino acid, glucose, and lipid kinetics during postabsorptive conditions before initiation, near the midpoint (after receiving 2,672 +/- 36 rads), and at completion (after receiving 6,072 +/- 307 rad) of a 6- to 8-week course of radiation therapy. Nutritional status was maintained throughout the treatment period by providing supplemental enteral feedings as needed. Postabsorptive plasma insulin, catecholamine, and amino acid concentrations did not change during the course of treatment. Before radiation therapy was initiated, values for the plasma rate of appearance (Ra) of urea (3.35 +/- 0.33 micromol x kg(-1) x min(-1)), alpha-ketoisocaproate ([alpha-KIC] 2.16 +/- 0.19 micromol x kg(-1) x min(-1)), phenylalanine (0.59 +/- 0.052 micromol x kg(-1) x min(-1)), and glucose (10.56 +/- 1.31 micromol x kg(-1) x min(-1)) were in the normal range. However, glycerol and palmitate Ra values (3.11 +/- 0.30 and 2.01 +/- 0.33 micromol x kg(-1) x min(-1), respectively) were 25% higher than values observed previously in normal subjects. Substrate flux did not change during radiation therapy, and measurements obtained during the midpoint and at completion of treatment were similar to initial values. These results demonstrate that large doses of radiation therapy, administered over 6 to 8 weeks to the upper body, do not cause significant metabolic stress.     

Intensified adjuvant cyclophosphamide, methotrexate and 5-fluorouracil therapy: a dose-finding study for ambulatory patients with breast cancer

Escalating doses of cyclophosphamide were given every 3 weeks as adjuvant treatment for women operated for breast cancer to determine the maximum tolerated dose of cyclophosphamide that can be given with constant doses of methotrexate (40 mg/m2) and 5-FU (600 mg/m2; CMF) as an outpatient treatment without the routine use of granulocyte colony-stimulating growth factor (G-CSF). The dose of cyclophosphamide was increased by 250 mg/m2 starting from the dose of 1,000 mg/m2. Mesna was given to prevent cystitis. The criteria for dose-limiting toxicity were grade IV granulocytopenia lasting for longer than 48 h, granulocytopenic infection or other grade IV toxicities. G-CSF and ofloxacin were used if grade IV granulocytopenia continued for longer than 48 h or if granulocytopenic infection occurred. At the dose level of 1,500 mg/m2 (500 mg/m2/week) 22 (92%) of the 24 patients had grade IV granulocytopenia during the 6 CMF cycles given, but only 3 (13%) had granulocytopenic fever. G-CSF was used in 28% of the cycles at this dose level. Other toxicities included complete alopecia (79%), nausea and vomiting. Sixteen (80%) of the premenopausal women became postmenopausal. At the dose level of 1,750 mg/m2 all 3 patients treated had to be hospitalized after the first cycle due to neutropenic infection (n = 2) or intractable vomiting even though prophylactic G-CSF was used. We conclude that intravenous CMF with a cyclophosphamide dose of 1,500 mg/m2 given at 3-week intervals with the selective use of prophylactic G-CSF is feasible as adjuvant treatment for patients with breast cancer.     

erbB-2, p53, and efficacy of adjuvant therapy in lymph node-positive breast cancer

BACKGROUND: We have previously reported that high expression of the erbB-2 gene (also known as HER-2/neu and ERBB2) in breast cancer is associated with patient response to dose-intensive treatment with cyclophosphamide, doxorubicin (Adriamycin), and 5-flurouracil (CAF) on the basis of short-term follow-up of 397 patients (set A) with axillary lymph node-positive tumors who were enrolled in Cancer and Leukemia Group B (CALGB) protocol 8541. METHODS: To validate those findings, we conducted immunohistochemical analyses of erbB-2 and p53 protein expression in an additional cohort of 595 patients (set B) from CALGB 8541, as well as a molecular analysis of erbB-2 gene amplification in tumors from all patients (sets A and B). Marker data were compared with clinical, histologic, treatment, and outcome data. RESULTS: Updated analyses of data from set A (median follow-up, 10.4 years) showed an even stronger interaction between erbB-2 expression and CAF dose, by use of either immunohistochemical or molecular data. A similar interaction between erbB-2 expression and CAF dose was observed in all 992 patients, analyzed as a single group. However, for set B alone (median follow-up, 8.2 years), results varied with the method of statistical analysis. By use of a proportional hazards model, the erbB-2 expression-CAF dose interaction was not significant for all patients. However, in the subgroups of patients randomly assigned to the high- or the moderate-dose arms, significance was achieved. When patient data were adjusted for differences by use of a prognostic index (to balance an apparent failure of randomization in the low-dose arm), the erbB-2 expression-CAF dose interaction was significant in all patients from the validation set B as well. An interaction was also observed between p53 immunopositivity and CAF dose. CONCLUSIONS: The hypothesis that patients whose breast tumors exhibit high erbB-2 expression benefit from dose-intensive CAF should be further validated before clinical implementation. Interactions between erbB-2 expression, p53 expression, and CAF dose underscore the complexities of predictive markers where multiple interactions may confound the outcome.     

Coronary artery operation in patients after breast cancer therapy

OBJECTIVE: The purpose of this investigation was to retrospectively study the outcome of patients undergoing coronary artery operation who were previously treated for breast cancer. METHODS: Between July 1992 and December 1996, 28 patients with a history of breast cancer underwent coronary artery bypass graft operation and were randomly matched against a noncancer group of similar size (n = 36) to allow for comparison of their preoperative characteristics, operative course, and postoperative outcome. RESULTS: The incidence of sternal wound infection was significantly higher in the cancer group than in the control group (25% versus 6%; p = 0.027). Postoperative noncardiac chest pain occurred more frequently in the cancer group than in the control group (52% versus 31%; not significant). In the study group, radiotherapy and recent myocardial infarction were the only two independent factors associated with sternal wound complications. Patients with a less than 17-year interval between the breast cancer therapy and the coronary artery operation had a higher incidence of sternal wound infection (46%) as opposed to patients with a longer time interval (7%; p = 0.028; odds ratio = 12). Sternal wound complications were more frequent in patients with a history of right-sided breast cancer (50%) compared with left-sided lesions (12.5%; p = 0.068; odds ratio = 7). CONCLUSIONS: Coronary artery operation in patients after breast cancer therapy may be associated with an increased sternal wound infection rate. To decrease this risk of infection, an approach through a right thoracotomy, minimally invasive techniques, the use of skeletonized internal mammary artery, and broad spectrum antibiotic therapy may be considered.     

Plasma insulin-like growth factor in primary breast cancer patients treated with adjuvant chemotherapy

Insulin-like growth factor 1 (IGF-1) plasma level was assayed in 60 breast cancer patients undergoing six courses of adjuvant chemotherapy. The only observed variation was a slight decrease (10%) in IGF-1 concentrations, assayed before treatment, between the first and the second courses of chemotherapy. During chemotherapy courses, there were no statistically significant variations in IGF-1. These results suggest that chemotherapy, unlike the specific hormonal treatments tamoxifen and somatostatin, certainly does not act via a decrease in plasma IGF-1.