RESUMO
PURPOSE: The purpose of this study was to determine the clinical, pathological, and treatment factors that are predictive of local-regional recurrence and overall survival for patients with breast cancer that is refractory to neoadjuvant chemotherapy. PATIENTS AND METHODS: This study analyzed the data of the 177 breast cancer patients treated on our institutional protocols who had less than a partial response to neoadjuvant chemotherapy. The initial clinical stage of disease was II in 27%, III in 69%, and IV (supraclavicular lymph node involvement) in 4%. Surgery was performed in 94% of the patients, and 77% of these patients also received adjuvant chemotherapy. RESULTS: After a median follow-up of 5.2 years, 106 patients experienced disease recurrence, with 98 of these having distant metastases and 45 having local-regional recurrence. The 5- and 10-year overall survivals for the entire group were 56% and 33%, respectively. The factors that were independently associated with a statistically significant poorer overall survival in a Cox regression analysis were pathologically involved lymph nodes after surgery, estrogen receptor-negative disease, and progressive disease during neoadjuvant chemotherapy. The 5-year overall survival for patients with pathologically negative lymph nodes ranged from 84% (estrogen receptor-positive disease) to 75% (estrogen re-ceptor-negative disease), compared with rates for patients with pathologically positive lymph nodes of 66% (estrogen receptor-positive disease) and 40% (estrogen receptor-negative disease). The 5-year survival of patients with progressive disease was only 19%. The 5- and 10-year local-regional recurrence rates for the 177 patients were 27% and 34%, respectively. Significant factors on Cox analysis that predicted for local-regional recurrence were four or more pathologically involved lymph nodes and estrogen receptor-negative disease. For the 105 patients treated with surgery and postoperative radiation therapy, the 10-year local-regional recurrence rates for the subgroups with 0, 1, or 2 of these factors were 12%, 25%, and 44%, respectively. CONCLUSIONS: For patients with a poor response to neoadjuvant chemotherapy, conventional treatments achieve reasonable outcomes in those with lymph node-negative disease or estrogen receptor-positive disease. However, more active systemic and local therapies are needed for patients with estrogen receptor-negative disease and positive lymph nodes and for those with clinical evidence of progressive disease during neoadjuvant chemotherapy.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Adulto , Análise de Variância , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Quimioterapia Adjuvante , Feminino , Humanos , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Recidiva Local de Neoplasia , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do TratamentoRESUMO
PURPOSE: Correlation between aging and doxorubicin-induced congestive heart failure in patients with metastatic breast cancer was studied to determine whether doxorubicin-induced congestive heart failure in elderly patients with metastatic breast cancer is a clinically significant issue. METHODS: This was a retrospective study with a median follow-up of 16.8 years. The setting was a comprehensive cancer center in a large city. A group of 682 consecutive patients with metastatic breast cancer presented to The University of Texas M.D. Anderson Cancer Center between 1973 and 1980. All patients received doxorubicin by bolus infusion. Patients in group 1 (n = 538) were aged 50 to 64 years; patients in group 2 (n = 144) were aged 65 years and older. Medical records of all patients were reviewed. Patients who had congestive heart failure were identified and analyzed. The diagnosis of doxorubicin-induced congestive heart failure was made and confirmed by a cardiologist at the time of its development. The main outcome measure was the cumulative probability of developing doxorubicin-induced congestive heart failure in elderly patients with metastatic breast cancer compared to a younger age group. RESULTS: In group 1, 33 patients, and in group 2, 13 patients developed doxorubicin-related congestive heart failure. The cumulative doses of doxorubicin administered to patients with congestive heart failure were 410 mg/m2 (range 150-550 mg/m2) and 400 (range 100-570 mg/m2), respectively. The time interval from the last date of doxorubicin treatment to the development of congestive heart failure was, respectively, 5 months (range < 1-65 months) and 9 months (range < 1-28 months). There was no statistically significant difference between the two congestive heart failure subgroups, nor were we able to identify risk factors that could have increased the risk of congestive heart failure among these patients. CONCLUSION: Older patients with metastatic breast cancer and no significant comorbidity can be treated with doxorubicin-based chemotherapy with no added risk of developing congestive heart failure beyond that in the younger age group.
Assuntos
Antibióticos Antineoplásicos/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Doxorrubicina/efeitos adversos , Insuficiência Cardíaca/induzido quimicamente , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , Estudos RetrospectivosRESUMO
PURPOSE/OBJECTIVES: To describe the new oral chemotherapeutic agent capecitabine (Xeloda, Roche Laboratories Inc., Nutley, NJ) and key concepts driving its development and to delineate the nursing impact of patient-administered, home-based chemotherapies. DATA SOURCES: Published papers, investigational materials, package inserts, and clinical experience. DATA SYNTHESIS: Capecitabine recently was approved to treat metastatic breast cancer refractory to paclitaxel and anthracycline-containing regimens. Efficacy has been demonstrated. However, although the current regimen is well-tolerated, > or = 40% of patients require dose modification because of grade 2 or greater toxicity, usually hand-foot syndrome or gastrointestinal symptoms. CONCLUSIONS: Capecitabine frees nurses from infusion-related workload, allowing and demanding a new type and level of patient education. Such education emphasizes compliance with the treatment plan and prevention, timely recognition, and management of toxicities. These practice changes also challenge nurses to advocate for reimbursement of educational practices. IMPLICATIONS FOR NURSING PRACTICE: Oncology nurses will play more of a central role as use of patient-administered, home-based therapies increases. Nurses must enhance their patient-education and telephone symptom-management skills and help to secure reimbursement for such activities.
Assuntos
Antineoplásicos/uso terapêutico , Desoxicitidina/análogos & derivados , Neoplasias/enfermagem , Cuidados de Enfermagem , Enfermagem Oncológica , Educação de Pacientes como Assunto , Administração Oral , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Capecitabina , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Desoxicitidina/uso terapêutico , Fluoruracila/análogos & derivados , Humanos , Neoplasias/tratamento farmacológicoRESUMO
BACKGROUND: The authors report results and long term follow-up for 1581 patients with metastatic breast carcinoma treated with doxorubicin-containing combination chemotherapy at a single institution; this report is meant to serve as a reliable reference for single-arm studies of newer therapies in this patient population. METHODS: Prospectively collected data from 18 successive doxorubicin-containing protocols for the treatment of metastatic breast carcinoma were evaluated. RESULTS: The response rate was 65.0% (95% confidence interval [CI]: 62.5-67.3%), complete response (CR) rate was 16.6% (95% CI: 14.8-18.6%), and partial response (PR) rate was 48.5% (95% CI: 46.0-50.9%). Median progression free survival (PFS) was 11.5 months (95% CI: 10.9-12.3 months) and median overall survival (OS) was 21.3 months (95% CI: 20.3-22.7 months). Survival correlated with response to therapy; median PFS and OS were 22.4 and 41.8 months, respectively, for the patients who achieved CR (n=263) and 14 and 24.6 months, respectively, for PR patients (n=766). The median OS of patients who had progressive disease during chemotherapy was 3.8 months. The response rate, PFS and OS correlated with number of organs involved and especially with tumor burden. Patients with hormone receptor-positive tumors had a similar response rate to that of patients with hormone receptor negative tumors but had significantly longer PFS (medians of 14.3 and 8.7 months, respectively) and OS (medians of 28.6 and 18.1 months, respectively). CONCLUSIONS: In patients with metastatic breast carcinoma, doxorubicin-containing chemotherapy had a response rate of 65% and a CR rate of 16.6%. PFS and OS were 11.5 months and 21.3 months, respectively, for all responders and 22.4 months and 41.8 months, respectively, for those who had CR.
Assuntos
Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Doxorrubicina/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/mortalidade , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , Neoplasias Hormônio-Dependentes/tratamento farmacológico , Resultado do TratamentoRESUMO
BACKGROUND: Sialyl-Tn (STn) represents an aberrantly glycosylated mucin epitope that is expressed in breast carcinoma and other adenocarcinomas and is an important factor in the development of novel immunotherapeutic approaches. The primary aim of the current study was to investigate the influence of STn expression on the prognoses of patients with breast carcinoma. METHODS: A cohort of 207 women diagnosed with invasive breast carcinoma who were treated with anthracycline-containing adjuvant chemotherapy and were enrolled in a randomized clinical trial were studied. Expression of STn was determined by an immunohistochemical procedure in which the B72.3 monoclonal antibody was used. Kaplan-Meier and Cox proportional regression survival analyses were used to compare low STn and high STn patients. RESULTS: Forty-eight (23%) of the 207 specimens demonstrated high STn staining (>25% cells were immunoreactive). During a median follow-up of 5 years, high STn patients had worse disease free survival than low STn patients (55% vs. 74%, respectively; P = 0.03). High STn expression was significantly associated with age (P = 0.04) but not with other conventional prognostic markers. In multivariate analysis using the Cox regression model, high STn emerged as an independent prognostic indicator for disease free survival (hazard ratio [HR], 2.02; 95% confidence interval [CI], 1.09-3.73) and for overall survival (HR, 2.16; 95% CI, 0.95-4.92). CONCLUSIONS: The results of this study suggest that STn may be a valuable marker for identifying women at high risk of developing recurrent breast carcinoma who may be candidates for trials investigating new therapies in combination with standard adjuvant therapy.
Assuntos
Antígenos Glicosídicos Associados a Tumores/biossíntese , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Carcinoma Lobular/patologia , Adulto , Idoso , Anticorpos Monoclonais/análise , Anticorpos Antineoplásicos/análise , Biomarcadores Tumorais , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Carcinoma Ductal de Mama/tratamento farmacológico , Carcinoma Ductal de Mama/metabolismo , Carcinoma Lobular/tratamento farmacológico , Carcinoma Lobular/metabolismo , Quimioterapia Adjuvante , Estudos de Coortes , Ciclofosfamida/administração & dosagem , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Feminino , Fluoruracila/administração & dosagem , Humanos , Técnicas Imunoenzimáticas , Leucovorina/administração & dosagem , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Prognóstico , Vimblastina/administração & dosagemRESUMO
PURPOSE: Most of the data about high-dose chemotherapy (HDCT) for metastatic breast cancer are derived from phase II studies. The interpretation of these data depends on comparisons with data from properly selected historical control patients treated with standard therapy under similar circumstances. We report the long-term results of patients with metastatic breast cancer who were eligible for HDCT but were treated with doxorubicin-containing standard-dose chemotherapy. PATIENTS AND METHODS: Prospectively collected data from 18 successive doxorubicin-containing protocols for the treatment of metastatic breast cancer were evaluated. Using common eligibility criteria for HDCT, we identified patients who would have been candidates for HDCT. We analyzed response rates, progression-free survival (PFS), and overall survival (OS) for all patients, potential HDCT candidates, and noncandidates. RESULTS: A total of 1,581 patients was enrolled onto the 18 studies. Six hundred forty-five were HDCT candidates, and 936 were noncandidates. The complete response rate was 27% for HDCT candidates and 7% for noncandidates; median PFS was 16 and 8 months and median OS was 30 and 17 months, respectively. Survival rates for HDCT candidates and noncandidates, respectively, were 21% and 6% at 5 years and 7% and 2% at 10 years. CONCLUSION: This study suggests that encouraging results of single-arm trials of HDCT could partially be due to selection of patients with better prognoses and further stresses the importance of completing ongoing randomized trials of HDCT to assess the relative efficacy of HDCT in patients with metastatic breast cancer.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/patologia , Seleção de Pacientes , Neoplasias da Mama/mortalidade , Ciclofosfamida/administração & dosagem , Progressão da Doença , Doxorrubicina/administração & dosagem , Feminino , Fluoruracila/administração & dosagem , Seguimentos , Humanos , Pessoa de Meia-Idade , Prognóstico , Viés de Seleção , Taxa de SobrevidaRESUMO
PURPOSE: To determine the long-term clinical course of patients with metastatic breast cancer (MBC) who achieved a complete remission with doxorubicin-alkylating agent-containing combination chemotherapy programs. PATIENTS AND METHODS: To assess the long-term prognosis of MBC, we reviewed our experience with 1,581 patients treated on consecutive doxorubicin and alkylating agent-containing front-line treatment protocols between 1973 and 1982. Treatment was administered for a maximum duration of 2 years. Characteristics of long-term survivors were evaluated, and hazard rates for progression were calculated. RESULTS: From this group, 263 (16.6%) achieved complete responses (CR) and 49 (3.1%) remained in CR for more than 5 years. After a median duration of 191 months, 26 patients remain in first CR, four patients died in CR at times ranging from 118 to 234 months, 18 patients died of breast cancer, and one is alive with metastatic disease. Compared with the overall CR and total patient populations, the long-term CR group had more premenopausal patients, a younger median age, a lower tumor burden, and better performance status. The hazard function shows a substantial drop in risk of progression after approximately 3 years from initiation of therapy. Ten long-term CR patients developed second primary cancers: breast (3), ovary (2), pancreas (1), endometrium (1), colon (1), head and neck (1), and lung (1). CONCLUSION: Most patients with MBC treated with systemic therapies have only temporary responses to treatment, but some patients continue in CR following initial treatment. These data show that a small percentage of patients achieve long-term remissions with standard chemotherapy regimens. Remission consolidation strategies are needed.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , Segunda Neoplasia Primária/patologia , Prognóstico , Indução de Remissão , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do TratamentoRESUMO
BACKGROUND: Metastatic breast cancer in elderly patients is less often treated with chemotherapy than in younger patients because of concerns related to toxic effects and tolerance. This is especially the case with doxorubicin-containing regimens. METHODS: We conducted a retrospective study of 1011 consecutive patients with metastatic breast cancer treated with doxorubicin-based chemotherapy protocols between July 1973 and July 1984. Age was not an exclusion criterion. Patient characteristics, dose intensity, hematologic-related toxic effects, and the cause of death were analyzed. The Kaplan-Meier survival curves were plotted and tested by the generalized Wilcoxon test. RESULTS: Seven hundred sixty-seven patients aged between 50 and 64 years were identified. While the response rate was higher in the younger group, the overall survival curves were similar for the two groups (P = .06), as well as the time to progression of the disease (P = .15). The dose intensity was comparable between the groups (P = .49), as was the median platelet and white blood cell nadirs. Neutropenic fever occurred in 16% of each group (P = 83), and fever in 12% and 17% of each group, respectively (P = .05). Death from infections occurred in 3.1% and 3.2% of patients in the two groups, respectively (P = .82). CONCLUSION: Patients with metastatic breast carcinoma who are older than 65 years tolerate the acute side effects of doxorubicin-based combination chemotherapy as well as the younger age group. Time to progression of disease and the overall survival are similar for both groups. Doxorubicin-based regimens are safe and effective for patients older than 65 years.
Assuntos
Antibióticos Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Doxorrubicina/uso terapêutico , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Contagem de Células Sanguíneas , Neoplasias da Mama/sangue , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Causas de Morte , Feminino , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , Estudos Retrospectivos , Estatísticas não Paramétricas , Análise de Sobrevida , Resultado do TratamentoRESUMO
Seven hundred fifty-two patients with stage III disease (of those, 178 patients with inflammatory carcinoma) were treated with a combined modality approach at our institute in seven prospective studies. After three to four cycles of chemotherapy, each patient was treated with local therapy. An estimated 54% of patients with stage IIIA disease and 24% of patients with stage IIIB disease were free of disease. An estimated 30% of patients with inflammatory carcinoma of breast were free of disease beyond 10 years with this approach.
Assuntos
Adenocarcinoma/terapia , Neoplasias da Mama/terapia , Adenocarcinoma/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/patologia , Terapia Combinada , Intervalo Livre de Doença , Feminino , Humanos , Estadiamento de NeoplasiasRESUMO
Taxol, an antimicrotubule agent, has shown promise for efficacy in treatment of breast cancer, but severe hypersensitivity reactions led to cessation of many phase I clinical trials. Consequently, investigators and the National Cancer Institute recommended that phase I and II studies of this agent use 24-hour infusions and antiallergic medications. Using a premedication regimen effective in preventing hypersensitivity reactions, we have performed a phase II trial of taxol in patients with metastatic breast cancer. Taxol was administered to 25 patients at a dose of 250 mg/m2 by 24-hour infusion every 21 days. These patients had received only one prior chemotherapy regimen, either adjuvant to surgery or for metastatic disease; all but two had received doxorubicin. In 60% of the patients, the dominant site of disease was the viscera. All patients were assessable. In April 1991, at a median time on study of 9 months (range, 5-13+ months), the objective response rate was 56% (12% complete and 44% partial; 95% confidence interval, 35%-76%). Disease progressed in only 8% of the patients. The median number of courses of therapy was 11. Granulocytopenia was the dose-limiting toxic effect, but neutropenia with fever occurred in only 5% of 232 courses. A chronic glove-and-stocking neuropathy developed in most patients, but no allergic reactions occurred. We conclude that taxol is an active agent in the treatment of metastatic breast cancer and that it warrants continued study. Currently, we are conducting a phase I trial of taxol plus doxorubicin. Future trials should address the optimal effective dose, the optimal sequencing of combinations, mechanisms of drug resistance in tumors, and dose-limiting toxic effects (particularly cardiac toxic effects of taxol given as a single agent or in drug combinations).
Assuntos
Alcaloides/uso terapêutico , Antineoplásicos Fitogênicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Adulto , Idoso , Agranulocitose/induzido quimicamente , Alcaloides/efeitos adversos , Antineoplásicos Fitogênicos/efeitos adversos , Doxorrubicina/uso terapêutico , Avaliação de Medicamentos , Feminino , Cardiopatias/induzido quimicamente , Humanos , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Doenças Musculares/induzido quimicamente , Paclitaxel , Dor/induzido quimicamente , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Indução de Remissão , Neoplasias de Tecidos Moles/tratamento farmacológico , Neoplasias de Tecidos Moles/secundário , Trombocitopenia/induzido quimicamenteRESUMO
This phase II trial evaluated the clinical role of interferon (IFN) in overcoming tamoxifen (TAM) resistance in breast cancer. Twenty women and 1 man received recombinant alpha interferon (5 million units per meter squared intramuscularly, 5 times per week) plus TAM (10 mg orally, twice daily) for the treatment of metastatic breast cancer, either after failing tamoxifen therapy or as frontline hormonal therapy. Of the 9 evaluable patients with disease progression after an objective response to TAM, there were no partial or complete responses with the addition of IFN. Ten evaluable patients received TAM plus IFN as frontline hormonal therapy with 2 complete and 3 partial responses for an overall response rate (RR) of 50% (95% confidence interval = 19-81), a 71% RR for ER-positive patients (95% confidence interval = 29-96) and no responses in ER-unknown patients. Sixteen patients required dose reductions of IFN and 8 patients discontinued therapy due to toxicity. It is unlikely that the RR for TAM plus IFN is greater that than seen with TAM alone, or that the addition of IFN to TAM therapy can overcome clinical TAM resistance.