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.     

Respective roles of radiotherapy and chemotherapy in adjuvant treatment of cancer of the breast: theoretical importance and feasibility of chemoradiotherapy

Concomitant radiochemotherapy is of potential interest in the treatment of early stage breast cancer. Radiotherapy improves local control after both conservative surgery and mastectomy and in this last case also improves overall survival. Some questions however still exist concerning the role of the delay between surgery and radiotherapy on the efficacy of this treatment. Over 6 months, the benefit due to radiotherapy could be reduced. Adjuvant chemotherapy leads to improved survival in all categories of patients with breast cancer, either with or without axillary-node involvement. Anthracyclin-containing regimens seem to be the most efficient, but their superiority on "historical" standard regimens such as cyclophosphamide-methotrexate-5-fluorouracil has never been fully established. Chemotherapy and radiotherapy have synergistic effects. Used simultaneously, their effect on residual disease after surgery could be increased. Moreover, this therapeutic modality enables reduction of treatment duration as well as the delay between surgery and radiotherapy. Some studies have demonstrated the good tolerance of concomitant radiotherapy and FNC (5-fluoro-uracil, mitoxantrone and cyclophosphamide) or CMF. Three French randomized trials testing the value of concomitant vs sequential radiotherapy + chemotherapy are ongoing. However, careful and critical interpretation of survival data will be required to consider concomitant chemoradiotherapy as a standard adjuvant treatment of early stage breast cancer.     

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.     

A case of locally advanced breast cancer successfully treated with intra-arterial infusion chemotherapy of high-dose epirubicin

A case of locally advanced breast cancer was treated with intra-arterial infusion chemotherapy using high-dose epirubicin. The 1st and 2nd cycle consisted of 210 mg (day 1, 4, 7) and 150 mg (day 1, 4, 7), respectively. After completion of 2 cycles of the regimen, remarkable loco-regional control and improved QOL were obtained. Leucopenia (nadir; 1,000/mm3) was the dose limiting factor, but well-tolerated with supportive therapy. The patient underwent salvage surgery and maintenance intra-venous chemotherapy (epirubicin; 30 mg/3 weeks). At this writing, the patient is enjoying favorable QOL. These findings suggested that this modality was effective for cases with exctensive loco-regional involvement.     

Pulmonary toxicity of high-dose chemotherapy for breast cancer: a non-invasive approach to diagnosis and treatment

Drug-induced pulmonary toxicity is one of the most frequent non-hematologic toxicities in breast cancer patients receiving high-dose chemotherapy with cyclophosphamide, cisplatin and BCNU (CY/CDDP/BCNU). A non-invasive clinical scoring system was utilized in an attempt to diagnose and treat early lung toxicity in 64 consecutive breast cancer patients undergoing CY/CDDP/BCNU supported by peripheral blood progenitor cells. Following hospital discharge, patients who developed symptoms suggestive of lung toxicity were evaluated with physical examination, DLCO, 2-min walking oximetry and a chest radiograph. Clinically weighted scores were assigned as follows: crackles on lung exam, 2; decrease in corrected DLCO by > 10% from baseline, 3; decrease in O2 saturation by > or = 4% with a 2-min walk, 3; and interstitial infiltrates on chest radiograph, 3. Patients with scores > or = 6 were treated with prednisone (60 mg p.o. twice a day followed by a 2-month taper). Treatment was instituted in 37 patients (58%) a median of 56 days after high-dose chemotherapy. Steroid therapy was associated with rapid clinical improvement in most patients. No fatal complications or chronic pulmonary fibrosis was seen. This non-invasive clinical scoring system can be utilized as a model for the early diagnosis of lung toxicity. Further investigation is warranted for the development of preventative measures against this syndrome.     

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.     

Delayed pulmonary toxicity syndrome following high-dose chemotherapy and bone marrow transplantation for breast cancer

We have intensely followed 45 consecutive women who underwent high-dose chemotherapy (cyclophosphamide/cisplatin/BCNU) and autologous bone marrow transplant (HDC/ABMT) for primary breast cancer with pulmonary function testing and computed tomography at regular intervals up to 126 wk (median follow-up, 72 wk). Our results show a high incidence of interstitial pneumonitis requiring steroids (64%), but no deaths due to pulmonary toxicity. The DL(CO) reaches a nadir of 58.2 +/- SEM 3.4 (expressed as a percent of baseline value) 15-18 wk following HDC/ABMT, and marginally improves with time. To a much lesser extent, vital capacity is reduced with a parallel drop in FEV1, suggesting mild restrictive changes without significant obstruction. Patients who develop pulmonary symptoms of cough or dyspnea have a corresponding significantly greater and earlier decline in DL(CO). Chest computed tomography was neither sensitive nor specific for diagnosing pulmonary toxicity. For patients who received steroids for pulmonary toxicity, there was a subsequent improvement in DL(CO) of 17.1% (p = 0.0001). Because our patients do not fit with the recent definition of idiopathic pulmonary syndrome (IPS), we propose the term delayed pulmonary toxicity syndrome (DPTS) to better describe the milder form of lung toxicity seen in our patient population. We were unable to correlate the severity of DPTS with age, tobacco use, baseline pulmonary function, or systemic exposure to BCNU, cyclophosphamide, or cisplatin. These data suggest that factor(s) other than, or in addition to, chemotherapy systemic exposure can contribute to DPTS. Furthermore, early identification and institution of systemic corticosteroids may improve lung function.     

Surveillance versus adjuvant chemotherapy in stage I non-seminomatous testicular cancer: a decision analysis

In stage I non-seminomatous testicular cancer, the decision between surveillance and adjuvant chemotherapy rests heavily upon the valuation of quality of life. Decision analysis was used to assess at what relapse rate adjuvant chemotherapy is preferred when patients' and clinicians' evaluations are considered. Probabilities were obtained from the literature and from experts. Evaluations of the disease states were obtained from patients (n = 68) and clinicians (n = 50). Results from the model were compared with a treatment preference question, asking for the relapse rate directly. Adjuvant chemotherapy was preferred at relapse rates above 50% when patient evaluations were used. The evaluations of the disease states had a strong impact on the decision. Using clinician evaluations, adjuvant chemotherapy was preferred at relapse rates above 73%. The relapse rates from the treatment preference question were lower: 46% for patients and 35% for clinicians. The results indicate that when patient preferences are accounted for, adjuvant chemotherapy should be considered more often.     

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.     

Tandem and triple high-dose chemotherapy with autologous stem cell rescue in metastatic breast cancer

The purpose of this phase II study was to evaluate the therapeutic efficacy and toxicity of a tandem or triple high-dose chemotherapy (HDC) with autologous peripheral blood stem cell transplantation (PBSCT) in patients with metastatic breast cancer (MBC) as first line chemotherapy. Conventional chemotherapy consisted of two cycles of epirubicin 120 mg/m2 and ifosfamide 7500 mg/m2 in the case of tandem HDC and one cycle of paclitaxel 135 mg/m2, epirubicin 90 mg/m2 and ifosfamide 6000 mg/m2 in the case of triple HDC. Tandem HDC was composed of two cycles of epirubicin 180 mg/m2, ifosfamide 12000 mg/m2 and carboplatin 900 mg/m2. In the case of triple HDC, paclitaxel 180 mg/m2, etoposide 1500 mg/m2 and thiotepa 600 mg/m2 was added as the third cycle. Patients with tandem HDC (n = 20) were evaluable for both survival and toxicity, and patients with triple HDC (n = 21) only for toxicity because of short-term follow-up. Both tandem and triple HDC were well tolerated and could be safely administered. Non-hematological WHO grade 3 or 4 toxicities were mucositis (8), temporary renal insufficiency (1), myocardial infarction (1), and neuropathy (1). No toxic death occurred. The Kaplan-Meier estimates for 44-months without progression and the overall survival were 12% and 38% respectively. The median survival was 22 months (95% CI: 7.4-51.7 months) and the median progression-free interval 14 months (95% CI: 5.1-43.7 months). In a population with an unfavorable prognosis, tandem HDC showed similar efficacy as to that described in other phase II studies. Triple HDC seems not to improve patient outcome compared to tandem HDC, but a long-term follow up is required.     

Much ado about not...enough data: high-dose chemotherapy with autologous stem cell rescue for breast cancer

Among hematologic malignancies, there are three disorders whose behavior is governed principally by the abnormal proliferation of a malignant megakaryocytic clone or a product thereof. These disorders are essential thrombocythemia, agnogenic myeloid metaplasia, and acute megakaryoblastic leukemia. Although there are other myeloproliferative diseases that can have high platelet counts, the major pathobiology of those diseases most commonly results from the proliferation of other hematopoietic lineages. Despite the rarity of the three disorders of malignant megakaryopoiesis mentioned above, advances have been made in the diagnosis, prognosis, and treatment of these disorders in recent years. However, understanding of the cellular and especially molecular pathobiology lags far behind.     

Palliative chemotherapy with CMF after the same adjuvant regimen for breast cancer. The Breast Cancer Study Group

BACKGROUND: The results of palliative chemotherapy with cyclophosphamide, methotrexate and 5-fluorouracil (CMF) in patients with advanced breast cancer who received adjuvant therapy with the same regimen were investigated. RESULTS: Of 47 patients, 14 (30%) achieved an objective remission (median duration 9.5, range 5-21 months) and 8 (17%) stabilisation of disease (median duration 6, range 3-17 months). Objective remissions were observed in premenopausal as well as in postmenopausal women, in patients with all categories of dominant localisation of disease and regardless of the oestradiol receptor status of the primary tumour or eventual previous endocrine therapy. One of 4 and 13 of 43 patients who started palliative chemotherapy within or later than 12 months after the last adjuvant course obtained an objective remission. The median survival time from start of therapy of all treated patients was 12 (range 1-40) months. Patients with an objective remission or stable disease and patients with progressive disease had a median survival time of 20 (range 6-40) and 6 (range 1-35) months respectively (p < 0.0001). CONCLUSIONS: Palliative treatment with CMF should not be rejected for patients who have relapsed after adjuvant chemotherapy with the same modality.     

The toxicity of radiotherapy following high-dose chemotherapy with peripheral blood stem cell support in high-risk breast cancer: a preliminary analysis

High-dose chemotherapy with autologous bone marrow and/or peripheral blood stem cell (PBSC) support is increasingly employed in the adjuvant treatment of high-risk breast cancer. Subsequent radiotherapy has been reported to be associated with morbidity and mortality resulting from pulmonary toxicity. In addition, the course of radiation therapy may be hampered by excess myelosuppression. The aim of this study was to investigate the contribution to radiation-induced toxicity of a high-dose chemotherapy regimen (CTC) that incorporates cyclophosphamide, thiotepa and carboplatin, in patients with high-risk breast cancer. In two randomised single institution studies, 70 consecutive patients received anthracycline-containing adjuvant chemotherapy (FEC: 5-fluorouracil, epirubicin and cyclophosphamide) followed by radiotherapy to achieve maximal local control. Of these patients, 34 received high-dose CTC with autologous PBSC support. All patients tolerated the full radiation dose in the planned time schedule. Radiation pneumonitis was observed in 5 patients (7%), 4 of whom had undergone high-dose chemotherapy (P = 0.38). All 5 responded favourably to prednisone. Fatal toxicities were not observed. Myelosuppression did not require interruption or untimely discontinuation of the radiotherapy, although significant reductions in median nadir platelet counts and haemoglobin levels were observed in patients who had received high-dose chemotherapy (P = 0.0001). The median nadir of WBC counts was mildly but significantly decreased during radiotherapy (P = 0.01). Red blood cell or platelet transfusions were rarely indicated. Adequate radiotherapy for breast cancer can be safely administered after high-dose CTC with autologous PBSC support. Radiation-induced myelotoxicity is clearly enhanced following CTC, but this is of little clinical significance. Radiation pneumonitis after high-dose therapy may occur more often in patients with a history of lung disease or after a relatively high radiation dose to the chest wall. Other high-dose regimens, particularly those incorporating drugs with known pulmonary toxicity (such as BCNU), may predispose patients to radiation pneumonitis.     

Histologic regression of breast cancer after primary (neoadjuvant) chemotherapy

Primary (neoadjuvant) chemotherapy of locally advanced breast carcinomas is performed to locally reduce the tumour mass and to improve the operability. Recently, the indication for primary chemotherapy has been extended for preoperative treatment in breast conserving surgery. In an ongoing clinical trial we examined the resection specimens of 51 mammary carcinomas after primary chemotherapy. These patients had received a neoadjuvant therapy with epirubicin/cyclophosphamide for size reduction of large (> 3 cm) but operable tumours (pretreatment median tumour size 4.5 cm by mammography). The tumour response was evaluated pathologically and compared with the clinical tumour regression that was observed in over two-thirds of all cases. We classified the regressive changes using a semiquantitative scoring system from 0 to 4 (0 = no effect, 1 = resorption and tumour sclerosis, 2 = minimal residual invasive tumour [< 0.5 cm], 3 = residual noninvasive tumour only, 4 = no tumour detectable). The aim of this study was to evaluate the improvement of operability objectively and to correlate the histology of the primary tumour with the response to treatment. With invasive lobular carcinomas, the tumour size after therapy was reduced less than average and irrespective of the amount of histological tumour cell reduction, largely due to the stromal content of these neoplasms. Invasive ductal carcinomas with extensive or predominant intraductal component also underwent only a slight decrease in tumour size; this was because of the lack of tumour response with the intraductal component. Well differentiated tubular carcinomas were particularly resistant to primary chemotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)     

Primary chemotherapy for early breast cancer

The use of primary chemotherapy represents a novel approach being used with increasing frequency in the management of early breast cancer. Many studies now testify to the usefulness of this modality in increasing the frequency of breast conservation. The acceptance of high-risk breast cancer as a systemic, and therefore predominantly medical rather than a surgical, disease suggests, however, that its role is likely to be far more reaching. While some trials have so far suggested the possibility of a survival benefit for this approach, definitive conclusions are not yet possible and await the final mature results from several large randomized studies. Even if such studies do not show a large extra benefit for primary chemotherapy over existing adjuvant treatment, the use of the primary tumour as an in vivo model of individual chemosensitivity and the identification of molecular markers as early predictors of response, suggest that this approach will become an integral part of the modern multidisciplinary management of early breast cancer.