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.     

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.     

Characteristics and correlates of fatigue after adjuvant chemotherapy for breast cancer

PURPOSE: Clinical reports suggest that many breast cancer patients experience persistent fatigue as a long-term side effect of adjuvant chemotherapy treatment. To investigate this issue further, we examined the characteristics and correlates of fatigue in women who had completed adjuvant chemotherapy for breast cancer and in a comparison group of women with no history of cancer. PATIENTS AND METHODS: Participants were 61 women with breast cancer who had completed chemotherapy an average of 471 days previously and 59 women with no history of cancer. All participants completed standardized self-report measures of fatigue, sleep quality, menopausal symptoms, and coping and were administered a structured clinical interview to identify current and past psychiatric disorder. RESULTS: Compared with women with no history of cancer, former adjuvant chemotherapy patients reported more severe fatigue (P < .01) and worse quality of life because of fatigue (P < .05). More severe fatigue among patients was significantly (P < .05) related to poorer sleep quality, more menopausal symptoms, greater use of catastrophizing as a coping strategy, and current presence of a psychiatric disorder. CONCLUSION: These findings support the view that many breast cancer patients experienced heightened fatigue after completion of adjuvant chemotherapy treatment. Results yield a profile of women who are at increased risk for heightened fatigue after chemotherapy and suggest ways to intervene clinically to prevent or reduce fatigue in this patient population.     

The case for high-dose adjuvant chemotherapy in breast cancer: (I) theoretical considerations

Adjuvant systemic therapy of breast cancer is now a well-established treatment resulting in improved survival. However, the available evidence suggests that it is most unlikely that an individual woman will be cured as a consequence of such treatment. There is, therefore, a pressing need for more effective therapy, particularly for younger women whose degree of axillary nodal involvement indicates a high risk of subsequent relapse. The case for using myelo-ablative chemotherapy for such women is presented in this article. In a subsequent publication we will discuss the clinical data to suggest that such an approach is not only possible with acceptable toxicity, but also could actually offer the increased cure rate sought by clinicians and patients alike.     

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.     

A nursing rehabilitation program for women with breast cancer receiving adjuvant chemotherapy

PURPOSE/OBJECTIVES: To examine the effects of a comprehensive rehabilitation program on facilitating physical and psychosocial adaptation of women with breast cancer who are receiving adjuvant chemotherapy. DESIGN: Experimental. SETTING: Breast evaluation clinics of two New England medical centers with comprehensive cancer treatment programs. SAMPLE: 14 women (mean age = 44 years) receiving adjuvant chemotherapy for breast cancer (86% stage II) following surgical treatment. METHODS: Subjects were assigned randomly to the experimental group or the usual care group. Experimental group members began a structured exercise program of walking and attended support group meetings. All subjects were tested before beginning chemotherapy, during the course of chemotherapy, and one month following chemotherapy completion. MAIN RESEARCH VARIABLES: Performance status, physical functioning, psychosocial adjustment, self-concept and body image, and 12 symptoms (e.g., fatigue, nausea, anxiety). FINDINGS: Measures of physical performance, psychosocial adjustment, and symptom intensity revealed improved adaptation in subjects who completed the walking/support group program. CONCLUSIONS: Physical and psychosocial benefits from a modest walking exercise program and a support group are possible for patients receiving adjuvant chemotherapy. IMPLICATIONS FOR NURSING PRACTICE: Although more detailed research is necessary to answer some of the questions raised by this study, implementing the walking program and forming a support group are achievable in an outpatient setting.     

Conditioned side effects induced by cancer chemotherapy: Prevention through behavioral treatment.

Cancer patients receiving chemotherapy often experience nausea and vomiting that develop as a result of classical conditioning. In order to determine whether this nausea and vomiting could be delayed or prevented, 24 cancer patients were randomized either to a group that received progressive muscle relaxation training (PMRT) plus guided imagery (GI), or to a no-treatment control group. Relaxation training sessions were held before the initiation of chemotherapy and during the first three chemotherapy treatments. Results indicated that patients receiving PMRT and GI had significantly less nausea and vomiting and significantly lower blood pressures, pulse rates, and dysphoria, especially anxiety, than did control patients. Nurse observations corroborated patient reports. These data suggest that early training in PMRT and GI can reduce and perhaps prevent the development of conditioned nausea and vomiting, and can alleviate high anxiety levels in cancer patients who receive emetogenic chemotherapy. (16 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cardiac effects of adjuvant doxorubicin and radiation therapy in breast cancer patients

PURPOSE: To assess the cardiac effects of two different cumulative doses of adjuvant doxorubicin and radiation therapy (RT) in breast cancer patients. PATIENTS AND METHODS: Two hundred ninety-nine breast cancer patients were prospectively randomized to receive either five cycles (CA5) or 10 cycles (CA10) of adjuvant treatment with cyclophosphamide (500 mg/ m2) and doxorubicin (45 mg/m2) administered by intravenous bolus every 21 days. One hundred twenty-two of these patients also received RT. Estimates of the cardiac RT dose-volume were retrospectively categorized as low, moderate, or high. The risk of major cardiac events (congestive heart failure, acute myocardial infarction) was assessable in 276 patients (92%), with a median follow-up time of 6.0 years (range, 0.5 to 19.4). RESULTS: The estimated risk (95% confidence interval) of cardiac events per 100 patient-years was significantly higher for CA10 than for CA5 [1.7 (1.0 to 2.8) v 0.5 (0.1 to 1.2); P=.02]. The risk of cardiac events in CA5 patients, irrespective of the cardiac RT dose-volume, did not differ significantly from rates of cardiac events predicted for the general female population by the Framingham Heart Study. In CA10 patients, the incidence of cardiac events was significantly increased (relative risk ratio, 3.6; P < .00003) compared with the Framingham population, particularly in groups that also received moderate and high dose-volume cardiac RT. CONCLUSION: Conventional-dose adjuvant doxorubicin as delivered in the CA5 regimen by itself, or in combination with locoregional RT, was not associated with a significant increase in the risk of cardiac events. Higher doses of adjuvant doxorubicin (CA10) were associated with a threefold to fourfold increased risk of cardiac events. This appears to be especially true in patients treated with higher dose-volumes of cardiac RT. Larger studies with longer follow-up periods are needed to confirm these results.     

Dyadic coping in metastatic breast cancer.

Objective: Couples facing metastatic breast cancer (MBC) must learn to cope with stressors that can affect both partners’ quality of life as well as the quality of their relationship. Common dyadic coping involves taking a “we” approach, whereby partners work together to maintain their relationship while jointly managing their shared stress. This study prospectively evaluated whether common dyadic coping was associated with less cancer-related distress and greater dyadic adjustment for female MBC patients and their male partners. Design: Couples (N = 191) completed surveys at the start of treatment for MBC (baseline), and 3 and 6 months later. Main Outcome Measures: Cancer-related distress was assessed with the Impact of Events Scale; dyadic adjustment was assessed using the short-form of the Dyadic Adjustment Scale. Results: Multilevel models using the couple as the unit of analysis showed that the effects of common positive dyadic coping on cancer-related distress significantly differed for patients and their partners. Whereas partners experienced slightly lower levels of distress, patients experienced slightly higher levels of distress. Although patients and partners who used more common negative dyadic coping experienced significantly greater distress at all times, the association was stronger for patients. Finally, using more common positive dyadic coping and less common negative dyadic coping was mutually beneficial for patients and partners in terms of greater dyadic adjustment. Conclusion: Our findings underscore the importance of couples working together to manage the stress associated with MBC. Future research may benefit from greater focus on the interactions between patients and their partners to address ways that couples can adaptively cope together. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

p53 and c-erbB-2 as markers of resistance to adjuvant chemotherapy in breast cancer

Recent literature suggests that c-erbB-2 and p53 alteration might be linked to drug resistance. This study investigates the relation of c-erbB-2 oncoprotein overexpression and p53 protein accumulation with prognosis in patients with node-positive breast cancer (NPBC) and assesses the modifying effect of these markers on response to short (1-10 courses) or prolonged (> 10 courses) adjuvant chemotherapy. This study is based on 458 patients with NPBC diagnosed from 1980 to 1986, with an average of 10 years of follow-up. Marker expression was evaluated by immunohistochemical analysis on formalin-fixed, paraffin-embedded material with antibodies to c-erbB-2 and p53. c-erbB-2 was expressed in 17.2% of the cases, and 19.1% of the tumors stained positively for p53. By multivariate analysis, women with prolonged adjuvant chemotherapy had better survival than those with a short course of chemotherapy among patients whose tumor lacked c-erbB-2 oncoprotein expression (P = .0245) or p53 protein accumulation (P = .0477). Prolonged chemotherapy, however, was associated with little or no change in survival among patients whose tumor expressed those markers. The present study adds support to the hypothesis linking c-erbB-2 and p53 expression to drug resistance.     

Long-term follow-up of a randomized trial on adjuvant chemotherapy and hormonal therapy in locally advanced breast cancer

Epidemiological research on respiratory syncytial virus (RSV) infections in children was carried out at the Virology Laboratory, University Teaching Hospital (UTH), in Lusaka, Zambia, from January-December 1996. Specimens including 736 nasal washings and 2424 throat swabs were collected from children with acute respiratory infections (ARI) and tested for RSV by enzyme immunoassay and by virus isolation. RSV was isolated in 62 (4.1%) of 1496 throat swabs collected from March to September and was detected in 99 (16.3%) of 609 nasal washings from March to November. The average RSV isolation rate was 2.6% and the average RSV detection rate was 13.5%. The highest RSV isolation (8.1%) and detection (30.5%) rates were in June 1996. RSV antibody in the 278 serum specimens collected from Zambian children, who were hospitalized in the paediatric ward, UTH, was detected using a standard neutralization test. The antibody positive rate was 60-80% in children > 4 years. It is evident that RSV is one of the main causal agents of ARI in children in Zambia.     

p53 protein accumulation and response to adjuvant chemotherapy in premenopausal women with node-negative early breast cancer

Although beta-sheets represent a sizable fraction of the secondary structure found in proteins, the forces guiding the formation of beta-sheets are still not well understood. Here we examine the folding of a small, all beta-sheet protein, the E. coli major cold shock protein CspA, using both equilibrium and kinetic methods. The equilibrium denaturation of CspA is reversible and displays a single transition between folded and unfolded states. The kinetic traces of the unfolding and refolding of CspA studied by stopped-flow fluorescence spectroscopy are monoexponential and thus also consistent with a two-state model. In the absence of denaturant, CspA refolds very fast with a time constant of 5 ms. The unfolding of CspA is also rapid, and at urea concentrations above the denaturation midpoint, the rate of unfolding is largely independent of urea concentration. This suggests that the transition state ensemble more closely resembles the native state in terms of solvent accessibility than the denatured state. Based on the model of a compact transition state and on an unusual structural feature of CspA, a solvent-exposed cluster of aromatic side chains, we propose a novel folding mechanism for CspA. We have also investigated the possible complications that may arise from attaching polyhistidine affinity tags to the carboxy and amino termini of CspA.     

Effectiveness of biofeedback and relaxation training in reducing the side effects of cancer chemotherapy.

Assessed the effectiveness of electromyograph (EMG) and skin-temperature (ST) biofeedback and relaxation training (RXT) in reducing the aversiveness of cancer chemotherapy (CHEMO). 81 cancer patients (aged 18–75 yrs) were randomized to 1 of 6 groups formed by a 3?×?2 factorial design. Outcome was assessed with physiological, patient-reported, and nurse-reported indices taken over 5 consecutive CHEMO treatments. RXT patients showed decreases in nausea and anxiety during CHEMO and physiological arousal after CHEMO. EMG and ST biofeedback reduced some indices of physiological arousal but had no other effects on CHEMO side effects. RXT may be effective in reducing the adverse consequences of CHEMO. It is suggested that the positive effects found for biofeedback were due to the RXT that was given with the biofeedback, not to the biofeedback alone. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

An evaluation of early or delayed adjuvant chemotherapy in premenopausal patients with advanced breast cancer undergoing oophorectomy

We treated randomly 75 premenopausal patients with advanced breast cancer with combination chemotherapy (5-fluorouracil, cyclophosphamide and prednisone), either as an early adjunct to oophorectomy or as a delayed treatment upon appearance of progressive metastatic disease after operation. The group receiving early systemic chemotherapy enjoyed an improved response rate, an improved survival rate and, most importantly, an improved progression-free interval (median of 53 versus 17 weeks). With the exclusion of the group with early (within three weeks after oophorectomy) progression, the progression-free intervals had a median duration of 77 weeks in the early-treatment group versus 33 weeks in the control group. The early-progression group did exceedingly poorly, although systemic chemotherapy was employed at that juncture, having a median survival of 22 weeks as compared to 144 weeks in the immediate-treatment group and 105 weeks in the control group.