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1.
Br J Cancer ; 112(4): 630-5, 2015 Feb 17.
Artículo en Inglés | MEDLINE | ID: mdl-25584488

RESUMEN

PURPOSE: To study the impact of adjuvant trastuzumab among patients achieving a pathologic complete response (pCR) after trastuzumab-based neoadjuvant systemic therapy (NST). PATIENTS AND METHODS: Patients with primary HER2-positive breast cancer treated with trastuzumab-based NST were categorised according to adjuvant trastuzumab administration and pCR status. Adjuvant trastuzumab became standard of care in 2006, this was the main reason patients in our cohort did not receive adjuvant trastuzumab. Kaplan-Meier was used to estimate survival. A test for interaction between adjuvant trastuzumab and pCR was completed. FINDINGS: Of 589 patients, 203 (34.5%) achieved a pCR. After surgery, 109 (18.5%) patients in the entire cohort did not receive adjuvant trastuzumab. Among patients achieving a pCR, 31.3% received adjuvant trastuzumab compared with 68.8% among those who did not achieve a pCR (P=0.0006). Among patients achieving pCR, adjuvant trastuzumab did not further improve overall survival (OS) or relapse-free survival (RFS) (P=0.35 and P=0.93, respectively). Any benefit of adjuvant trastuzumab in OS and RFS among patients without a pCR did not achieve statistical significance (P=0.3 and P=0.44, respectively). CONCLUSIONS: In this cohort, patients treated with trastuzumab-based NST who achieved a pCR have excellent outcome regardless of whether they received adjuvant trastuzumab.


Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Carcinoma Ductal de Mama/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/administración & dosificación , Receptor ErbB-2/antagonistas & inhibidores , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/genética , Neoplasias de la Mama/mortalidad , Carcinoma Ductal de Mama/genética , Carcinoma Ductal de Mama/mortalidad , Quimioterapia Adyuvante , Ciclofosfamida/administración & dosificación , Epirrubicina/administración & dosificación , Femenino , Fluorouracilo/administración & dosificación , Humanos , Persona de Mediana Edad , Terapia Neoadyuvante , Paclitaxel/administración & dosificación , Receptor ErbB-2/genética , Estudios Retrospectivos , Trastuzumab
2.
Ann Oncol ; 19(12): 2020-5, 2008 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-18667396

RESUMEN

BACKGROUND: The aim of this study was to compare the extent of pathologic response in patients with HER2-positive (HER2+) breast cancer treated with standard neoadjuvant chemotherapy, with or without trastuzumab (H), according to hormone receptor (HR) status. PATIENTS AND METHODS: We included 199 patients with HER2+ breast cancer from three successive cohorts of neo-adjuvant chemotherapy on the basis of paclitaxel (Taxol) (P) administered weekly (w) or three weekly (3-w), followed by 5-fluorouracil (F), doxorubicin (A) or epirubicin (E), and cyclophosphamide (C). Residual cancer burden (RCB) was determined from pathologic review of the primary tumor and lymph nodes and was classified as pathologic complete response (pCR) or minimal (RCB-I), moderate (RCB-II), or extensive (RCB-III) residual disease. RESULTS: In HR-positive (HR+) cancers, a higher rate of pathologic response (pCR/RCB-I) was observed with concurrent H + 3-wP/FEC (73%) than with 3-wP/FEC (34%, P = 0.002) or wP/FAC (47%; P = 0.02) chemotherapy alone. In HR-negative (HR-) cancers, there were no significant differences in the rate of pathologic response (pCR/RCB-I) from 3-wP/FAC (50%), wP/FAC (68%), or concurrent H + 3-wP/FEC (72%). CONCLUSIONS: Patients with HR+/HER2+ breast cancer obtained significant benefit from addition of trastuzumab to P/FEC chemotherapy; pathologic response rate was similar to that seen in HR-/HER2+ breast cancers.


Asunto(s)
Anticuerpos Monoclonales/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasia Residual/prevención & control , Receptor ErbB-2/genética , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales Humanizados , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Ensayos Clínicos como Asunto , Ciclofosfamida/administración & dosificación , Doxorrubicina , Epirrubicina/administración & dosificación , Femenino , Fluorouracilo/administración & dosificación , Humanos , Persona de Mediana Edad , Terapia Neoadyuvante , Neoplasias Hormono-Dependientes/tratamiento farmacológico , Neoplasias Hormono-Dependientes/genética , Neoplasias Hormono-Dependientes/patología , Paclitaxel/administración & dosificación , Ensayos Clínicos Controlados Aleatorios como Asunto , Receptor ErbB-2/biosíntesis , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/metabolismo , Trastuzumab
3.
Anticancer Agents Med Chem ; 8(5): 481-7, 2008 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-18537531

RESUMEN

Although significant advances have been made in the treatment of breast cancer using chemotherapy, less than half of the patients treated for localized breast cancer benefit from adjuvant chemotherapy and most patients with metastatic cancer eventually develop disease that is chemotherapy resistant. Targeted agents, such as inhibitors of tyrosine kinases, offer the opportunity to reverse chemotherapy resistance and enhance response in patients with localized and advanced breast cancer. Such combined approaches have been established for the treatment of advanced breast cancer and are now demonstrating benefit in the adjuvant arena. This review summarizes the results of several trials involving the use of tyrosine kinase inhibition in combination with chemotherapy for the treatment of breast cancer and discusses future directions for breast cancer biotherapy.


Asunto(s)
Antineoplásicos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/uso terapéutico , Proteínas Tirosina Quinasas Receptoras/antagonistas & inhibidores , Quimioterapia Adyuvante , Ensayos Clínicos como Asunto , Terapia Combinada , Humanos
4.
Ann Oncol ; 19(3): 420-32, 2008 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-17906299

RESUMEN

Bisphosphonates (BP) prevent, reduce, and delay cancer-related skeletal complications in patients, and have substantially decreased the prevalence of such events since their introduction. Today, a broad range of BP with differences in potency, efficacy, dosing, and administration as well as approved indications is available. In addition, results of clinical trials investigating the efficacy of BP in cancer treatment-induced bone loss (CTIBL) have been recently published. The purpose of this paper is to review the current evidence on the use of BP in solid tumours and provide clinical recommendations. An interdisciplinary expert panel of clinical oncologists and of specialists in metabolic bone diseases assessed the widespread evidence and information on the efficacy of BP in the metastatic and nonmetastatic setting, as well as ongoing research on the adjuvant use of BP. Based on available evidence, the panel recommends amino-bisphosphonates for patients with metastatic bone disease from breast cancer and zoledronic acid for patients with other solid tumours as primary disease. Dosing of BP should follow approved indications with adjustments if necessary. While i.v. administration is most often preferable, oral administration (clodronate, IBA) may be considered for breast cancer patients who cannot or do not need to attend regular hospital care. Early-stage cancer patients at risk of developing CTIBL should be considered for preventative BP treatment. The strongest evidence in this setting is now available for ZOL. Overall, BP are well-tolerated, and most common adverse events are influenza-like syndrome, arthralgia, and when used orally, gastrointestinal symptoms. The dose of BP may need to be adapted to renal function and initial creatinine clearance calculation is mandatory according to the panel for use of any BP. Subsequent monitoring is recommended for ZOL and PAM, as described by the regulatory authority guidelines. Patients scheduled to receive BP (mainly every 3-4 weeks i.v.) should have a dental examination and be advised on appropriate measures for reducing the risk of jaw osteonecrosis. BP are well established as supportive therapy to reduce the frequency and severity of skeletal complications in patients with bone metastases from different cancers.


Asunto(s)
Difosfonatos/uso terapéutico , Neoplasias/tratamiento farmacológico , Osteoporosis/prevención & control , Guías de Práctica Clínica como Asunto , Antineoplásicos/efectos adversos , Densidad Ósea/efectos de los fármacos , Neoplasias Óseas/complicaciones , Neoplasias Óseas/secundario , Neoplasias de la Mama/terapia , Carcinoma/secundario , Carcinoma/terapia , Femenino , Humanos , Neoplasias Renales/terapia , Neoplasias Pulmonares/terapia , Masculino , Neoplasias/complicaciones , Osteonecrosis/prevención & control , Osteoporosis/etiología , Neoplasias de la Próstata/terapia
5.
Ann Oncol ; 18(5): 874-80, 2007 May.
Artículo en Inglés | MEDLINE | ID: mdl-17293601

RESUMEN

BACKGROUND: We examined if inclusion of a taxane and more prolonged preoperative chemotherapy improves pathologic complete response (pCR) rate in estrogen receptor (ER)-positive breast cancer compared with three to four courses of 5-fluorouracil, doxorubicin, cyclophosphamide (FAC). PATIENTS AND METHODS: Pooled analysis of results from seven consecutive neo-adjuvant chemotherapy trials including 1079 patients was carried out. These studies were conducted at MD Anderson Cancer Center from 1974 to 2001. Four hundred and twenty-six (39.5%) patients received taxane-based neo-adjuvant therapy. pCR rates and survival times were analyzed as a function of chemotherapy regimen and ER status. Multivariate logistic and Cox regression analysis were carried out to identify variables associated with pCR and survival. RESULTS: Patients with ER-negative cancer had higher overall pCR rate than patients with ER-positive tumors (20.1% versus 4.9%, P < 0.001). In ER-negative patients, the pCR rates were 29% and 15% with and without a taxane (P < 0.001). In ER-positive patients, the pCR rates were 8.8% and 2.0% with and without a taxane (P < 0.001). In multivariate analysis, clinical tumor size (P < 0.001), ER-negative status (P < 0.001) and inclusion of a taxane (P = 0.01) were independently associated with pCR. For patients with pCR, survival was similar regardless of ER status or the type of regimen that induced pCR. CONCLUSION: pCR rates increased for patients with both ER-positive and ER-negative tumors as regimens started to include a taxane and became longer. This indicates that a subset of patients with ER-positive breast cancer benefits from more aggressive chemotherapy, similarly to patients with ER-negative tumors.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Neoplasias Hormono-Dependientes/tratamiento farmacológico , Paclitaxel/análogos & derivados , Paclitaxel/administración & dosificación , Receptores de Estrógenos/metabolismo , Adulto , Anciano , Neoplasias de la Mama/clasificación , Neoplasias de la Mama/patología , Hidrocarburos Aromáticos con Puentes , Quimioterapia Adyuvante , Ciclofosfamida/uso terapéutico , Doxorrubicina/uso terapéutico , Esquema de Medicación , Femenino , Fluorouracilo/uso terapéutico , Humanos , Persona de Mediana Edad , Neoplasias Hormono-Dependientes/cirugía , Pronóstico , Análisis de Supervivencia , Taxoides , Carga Tumoral/efectos de los fármacos
6.
J Clin Oncol ; 22(12): 2284-93, 2004 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-15136595

RESUMEN

PURPOSE: The goal of this study was to examine the feasibility of developing a multigene predictor of pathologic complete response (pCR) to sequential weekly paclitaxel and fluorouracil + doxorubicin + cyclophosphamide (T/FAC) neoadjuvant chemotherapy regimen for breast cancer. PATIENTS AND METHODS: All patients underwent one-time pretreatment fine-needle aspiration to obtain RNA from the cancer for transcriptional profiling using cDNA arrays containing 30721 human sequence clones. Analysis was performed after profiling, and 42 patients' clinical results were available, 24 of which were used for predictive marker discovery; 18 patients' results were used as an independent validation set. RESULTS: Thirty-one percent of patients had pCR (six discovery and seven validation), defined as disappearance of all invasive cancer in the breast after completion of chemotherapy. We could identify no single marker that was sufficiently associated with pCR to be used as an individual predictor. A multigene model with 74 markers (P

Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Ciclofosfamida/uso terapéutico , Doxorrubicina/uso terapéutico , Fluorouracilo/uso terapéutico , Perfilación de la Expresión Génica , Paclitaxel/administración & dosificación , Adulto , Anciano , Quimioterapia Adyuvante , Estudios de Factibilidad , Humanos , Persona de Mediana Edad , Terapia Neoadyuvante , Pronóstico , Resultado del Tratamiento
7.
Cancer ; 92(7): 1775-82, 2001 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-11745249

RESUMEN

BACKGROUND: Inflammatory breast carcinoma (IBC) is a rare but aggressive form of breast carcinoma. Anthracycline-based regimens represent the standard of treatment for IBC. Reports of significant clinical activity of paclitaxel in metastatic breast carcinoma led the authors to investigate the role of this drug in the management of IBC. METHODS: Forty-four patients with IBC were enrolled between February 1994 and January 1998. The treatment plan consisted of induction chemotherapy (IC), mastectomy, adjuvant chemotherapy, and radiotherapy. Forty-two patients received IC with four cycles of fluorouracil, doxorubicin, and cyclophosphamide. If the clinical response was less than partial, patients were "crossed over" to paclitaxel before mastectomy. All patients received adjuvant paclitaxel. Patients unresectable after paclitaxel were offered high-dose chemotherapy with autologous peripheral blood progenitor cell support. RESULTS: Thirty-four patients (81%) achieved an objective clinical remission; 3 patients (7%) achieved a clinical complete remission, 31 (74%) a partial remission. Six patients (14%) achieved pathologic complete remission. Sixteen patients were treated with paclitaxel, 7 of them (44%) were able to undergo mastectomy. Median time to progression (TTP) was 22 months. Median overall survival (OS) was 46 months. Concordance between clinical and pathologic response was documented in only 8 patients (24%). No differences in TTP and OS compared with a historical group of 178 IBC patients treated with anthracycline-based regimens. CONCLUSIONS: Paclitaxel improves tumor resectability in anthracycline-refractory IBC. The impact of paclitaxel on the prognosis of IBC needs to be better evaluated in future trials using more dose-intensive schedules of administration. New imaging modalities may contribute to improve assessment of response to IC.


Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Antineoplásicos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Paclitaxel/uso terapéutico , Adenocarcinoma/radioterapia , Adenocarcinoma/cirugía , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/radioterapia , Neoplasias de la Mama/cirugía , Terapia Combinada , Ciclofosfamida/administración & dosificación , Doxorrubicina/administración & dosificación , Femenino , Fluorouracilo/administración & dosificación , Humanos , Mastectomía , Persona de Mediana Edad , Inducción de Remisión , Análisis de Supervivencia
8.
Semin Oncol ; 28(5 Suppl 16): 33-40, 2001 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-11706394

RESUMEN

One of the primary objectives of early clinical drug development is to determine the optimal dose and schedule of administration of the drug under study. If this objective is accomplished, subsequent clinical trials can truly evaluate the antitumor efficacy, tolerability, and safety of the new drug, and the appropriate assessment of benefit/risk can be made. A full understanding of the mechanisms not only of antitumor activity but also of side effects and toxicity is critical to select the optimal schedule of administration. In this regard, preclinical (in vitro and in vivo) studies are often helpful before clinical studies are initiated. However, no preclinical model is fully predictive of the outcome of human clinical trials. Therefore, while preclinical studies can point to potentially fruitful directions in clinical investigation, only after fairly substantial clinical experience does the medical community reach agreement and understanding of the optimal dose and schedule of administration of an agent. For some agents, these conclusions are reached early in the development of the drug (eg, cyclophosphamide, docetaxel). For others (eg, fluorouracil, cytosine arabinoside) the definition of optimal dose and schedule of administration is a never-ending story. The optimal duration of administration for trastuzumab is not known and is currently under active investigation.


Asunto(s)
Anticuerpos Monoclonales/administración & dosificación , Antineoplásicos/administración & dosificación , Neoplasias de la Mama/tratamiento farmacológico , Anticuerpos Monoclonales Humanizados , Evaluación Preclínica de Medicamentos , Humanos , Neoplasias Hormono-Dependientes/tratamiento farmacológico , Ensayos Clínicos Controlados Aleatorios como Asunto , Receptor ErbB-2 , Trastuzumab
9.
Am J Surg ; 182(6): 601-8, 2001 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-11839324

RESUMEN

BACKGROUND: This study was performed to investigate the extent of tumor downstaging achieved in women with operable breast cancer treated with neoadjuvant chemotherapy and breast-conservation surgery, develop recommendations for effective surgical planning, and report local-regional recurrence rates with this approach. METHODS: One hundred nine patients with stage II or III (T3N1) breast cancer were treated in three prospective trials utilizing four cycles of 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC, n = 72) or paclitaxel (n = 37) followed by segmental resection (n = 109) and axillary node dissection (n = 94). Postoperatively, patients received 4 additional cycles of FAC followed by irradiation of the breast. The median follow-up was 53 months. RESULTS: The median tumor size was 4 cm (range 1.1 to 9 cm) at presentation and only 1 cm (range 0 to 4.5 cm) after four cycles of chemotherapy. The primary tumor could not be palpated after chemotherapy in 55% of 104 patients presenting with a palpable mass and therefore required needle localization or ultrasound guidance for surgical resection. Of the 34 patients clinically deemed to have no residual carcinoma in the breast after chemotherapy and before surgery, only 50% of these patients were found to have no residual carcinoma on pathologic examination after surgery. Patients with primary tumors < or =2 cm were significantly more likely than patients with larger tumors to have complete eradication of the primary tumor prior to surgery (P <0.001). The 5-year local-regional recurrence rate was 5%. CONCLUSIONS: Tumor downstaging is marked in patients with operable breast cancer and requires close monitoring during chemotherapy. We recommend placement of metallic tumor markers when the primary tumor is < or =2 cm to facilitate adequate resection and pathologic processing. Resection of the tumor bed remains necessary in women deemed to have a complete clinical response to ensure low rates of recurrence.


Asunto(s)
Neoplasias de la Mama/terapia , Quimioterapia Adyuvante , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/cirugía , Ciclofosfamida/administración & dosificación , Doxorrubicina/administración & dosificación , Femenino , Fluorouracilo/administración & dosificación , Humanos , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Estadificación de Neoplasias , Paclitaxel/administración & dosificación , Planificación de Atención al Paciente , Estudios Prospectivos , Ultrasonografía
10.
J Natl Cancer Inst Monogr ; (30): 72-9, 2001.
Artículo en Inglés | MEDLINE | ID: mdl-11773296

RESUMEN

Substantial progress has been made in the multidisciplinary management of primary breast cancer during the last 30 years. Adjuvant chemotherapy has been shown to significantly reduce the annual risk of cancer recurrence and mortality, and these effects persist even 15 years after diagnosis. Combination chemotherapy is superior to single-agent therapy and anthracycline-containing regimens. Those that combine an anthracycline with 5-fluorouracil and cyclophosphamide are more effective than regimens without an anthracycline. Six cycles of a single regimen appear to provide optimal benefit. Dose reductions below the standard range are associated with inferior results. Dose increases that require growth factor or hematopoietic stem cell support are under investigation; at this time, the existing results provide no compelling reason to use this strategy outside a clinical trial. Regimens using fixed crossover designs with two non-cross-resistant regimens are being evaluated. The addition of a taxane to anthracycline-containing regimens is currently under intense scrutiny, and preliminary analysis of the first three clinical trials has shown encouraging, albeit not compelling, results. For patients with estrogen receptor-positive breast cancer, the sequential administration of chemotherapy and 5 years of tamoxifen therapy provides additive benefits. No compelling evidence exists to combine ovarian ablation with chemotherapy. Most side effects and toxic effects are self-limited, although premature menopause requires monitoring and preventive interventions to preserve bone mineral density. The small risk of acute leukemia is of concern, and additional research to develop safer regimens is clearly indicated. The overall effect of optimal local/regional treatment combined with an anthracycline-containing adjuvant chemotherapy and a taxane (and, for patients with estrogen receptor-positive tumors, 5 years of tamoxifen therapy) is a greater than 50% reduction in annual risks of recurrence of and death from breast cancer. For most patients at intermediate or high risk of cancer recurrence, the benefits of adjuvant chemotherapy exceed by far its unwanted effects.


Asunto(s)
Antineoplásicos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Quimioterapia Adyuvante , Taxoides , Antraciclinas/uso terapéutico , Antineoplásicos/administración & dosificación , Hidrocarburos Aromáticos con Puentes/uso terapéutico , Quimioterapia Adyuvante/métodos , Quimioterapia Adyuvante/estadística & datos numéricos , Sinergismo Farmacológico , Hormonas/uso terapéutico , Humanos , Factores de Tiempo , Resultado del Tratamiento
11.
Cancer ; 88(5): 1082-90, 2000 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-10699899

RESUMEN

BACKGROUND: Pamidronate therapy previously has been shown to reduce skeletal complications effectively for up to 12 months in breast carcinoma patients with bone metastases. The current study data provide further follow-up results regarding the effects of long term (up to 24 months) pamidronate treatment in women with breast carcinoma and osteolytic metastases. METHODS: Follow-up results from two prospective, multicenter, randomized, double-blind, placebo-controlled intervention trials conducted at academic and community oncology centers were combined to provide a large data set with which to evaluate the long term efficacy and safety of pamidronate therapy. Seven hundred fifty-four women with Stage IV breast carcinoma and osteolytic metastases were randomized to the 2 treatment arms of the trial. Three patients were excluded from the intent-to-treat population for the analysis. A total of 751 evaluable patients were randomized to receive either a 90-mg intravenous pamidronate infusion (367 patients) or a placebo infusion (384 patients) every 3-4 weeks. The primary outcome measures were skeletal morbidity rate (events/year), proportion of patients developing a skeletal complication, and time to first skeletal complication. RESULTS: Of the 367 women receiving pamidronate, 115 (31.3%) completed the trial and 81 (22.1%) discontinued the study due to adverse events. Of the 384 women who received placebo, 100 (26.0%) completed the study and 76 (19.8%) discontinued the study due to adverse events. The skeletal morbidity rate was 2.4 in the pamidronate group and 3.7 in the placebo group (P < 0.001). In the pamidronate group, 186 of the 367 patients (51%) had skeletal complications compared with 246 of the 384 patients in the placebo group (64%) (P < 0.001). The median time to first skeletal complication was 12.7 months in the pamidronate group and 7 months in the placebo group (P < 0.001). Six patients treated with pamidronate discontinued treatment due to drug-related adverse events. Pain and analgesic scores were significantly worse in the placebo group compared with those patients in the pamidronate group. CONCLUSIONS: In the current study, monthly infusions of 90 mg of pamidronate as a supplement to antineoplastic therapy were found to be well tolerated and superior to antineoplastic therapy alone in preventing skeletal complications and palliating symptoms for at least 24 months in breast carcinoma patients with osteolytic bone metastases.


Asunto(s)
Antineoplásicos/uso terapéutico , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/secundario , Neoplasias de la Mama/patología , Difosfonatos/uso terapéutico , Osteólisis/prevención & control , Cuidados Paliativos , Anciano , Antineoplásicos/efectos adversos , Neoplasias Óseas/patología , Neoplasias de la Mama/complicaciones , Difosfonatos/efectos adversos , Método Doble Ciego , Femenino , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Osteólisis/complicaciones , Osteólisis/patología , Dolor/etiología , Pamidronato , Estudios Prospectivos , Calidad de Vida
12.
Am J Clin Oncol ; 23(1): 40-1, 2000 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-10683074

RESUMEN

Twelve women with metastatic breast cancer were treated with continuous infusion high dose leucovorin, 5-fluorouracil and cisplatin. Toxicity was severe although the dose was lower than previously described for the treatment of other cancers, and there was little anti-tumor activity. Many other regimens are more effective and less toxic.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias de la Mama/patología , Cisplatino/administración & dosificación , Femenino , Fluorouracilo/administración & dosificación , Humanos , Leucovorina/administración & dosificación , Persona de Mediana Edad , Metástasis de la Neoplasia
13.
J Natl Cancer Inst ; 92(3): 225-33, 2000 Feb 02.
Artículo en Inglés | MEDLINE | ID: mdl-10655439

RESUMEN

BACKGROUND: Uncontrolled studies have reported encouraging outcomes for patients with high-risk primary breast cancer treated with high-dose chemotherapy and autologous hematopoietic stem cell support. We conducted a prospective randomized trial to compare standard-dose chemotherapy with the same therapy followed by high-dose chemotherapy. PATIENTS AND METHODS: Patients with 10 or more positive axillary lymph nodes after primary breast surgery or patients with four or more positive lymph nodes after four cycles of primary (neoadjuvant) chemotherapy were eligible. All patients were to receive eight cycles of 5-fluorouracil, doxorubicin (Adriamycin), and cyclophosphamide (FAC). Patients were stratified by stage and randomly assigned to receive two cycles of high-dose cyclophosphamide, etoposide, and cisplatin with autologous hematopoietic stem cell support or no additional chemotherapy. Tamoxifen was planned for postmenopausal patients with estrogen receptor-positive tumors and chest wall radiotherapy was planned for all. All P values are from two-sided tests. RESULTS: Seventy-eight patients (48 after primary surgery and 30 after primary chemotherapy) were registered. Thirty-nine patients were randomly assigned to FAC and 39 to FAC followed by high-dose chemotherapy. After a median follow-up of 6.5 years, there have been 41 relapses. In intention-to-treat analyses, estimated 3-year relapse-free survival rates were 62% and 48% for FAC and FAC/high-dose chemotherapy, respectively (P =.35), and 3-year survival rates were 77% and 58%, respectively (P =.23). Overall, there was greater and more frequent morbidity associated with high-dose chemotherapy than with FAC; there was one septic death associated with high-dose chemotherapy. CONCLUSIONS: No relapse-free or overall survival advantage was associated with the use of high-dose chemotherapy, and morbidity was increased with its use. Thus, high-dose chemotherapy is not indicated outside a clinical trial.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/cirugía , Trasplante de Células Madre Hematopoyéticas , Adulto , Anciano , Neoplasias de la Mama/patología , Quimioterapia Adyuvante , Ciclofosfamida/administración & dosificación , Supervivencia sin Enfermedad , Doxorrubicina/administración & dosificación , Esquema de Medicación , Femenino , Fluorouracilo/administración & dosificación , Estudios de Seguimiento , Humanos , Metástasis Linfática , Persona de Mediana Edad , Terapia Neoadyuvante , Estudios Prospectivos , Radioterapia Adyuvante , Análisis de Supervivencia , Trasplante Autólogo , Resultado del Tratamiento
14.
J Clin Oncol ; 17(11): 3412-7, 1999 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-10550135

RESUMEN

PURPOSE: To compare prospectively the antitumor activity of single-agent paclitaxel to the three-drug combination of fluorouracil, doxorubicin, and cyclophosphamide (FAC) as neoadjuvant therapy in patients with operable breast cancer. PATIENTS AND METHODS: Patients with T1-3N0-1M0 disease were randomized to receive either paclitaxel (250 mg/m(2)) as 24-hour infusion or FAC in standard doses at every-3-week intervals. Each patient was treated with four cycles of preoperative chemotherapy. Clinical response and extent of residual disease in the breast and lymph nodes was assessed after four cycles of induction chemotherapy. RESULTS: A total of 174 patients were registered, and 87 were randomized to each arm of the study. Clinical response, ie, complete and partial responses, was similar in both arms of the study. Three patients in the FAC arm and one patient in the paclitaxel subgroup had progressive disease. The extent of residual disease by intent-to-treat analysis at the time of surgery was similar between the two arms of the study. CONCLUSION: The results of this prospective study demonstrated that single-agent paclitaxel as neoadjuvant therapy has significant antitumor activity, and this was clinically comparable to FAC. Similar fractions of patients had clinical complete and partial responses, and very few patients had no response to either therapy. The value of alternate non-cross-resistant therapies as used in this protocol on the clinical course of this disease would require longer follow-up.


Asunto(s)
Antineoplásicos Fitogénicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Paclitaxel/uso terapéutico , Adulto , Anciano , Antineoplásicos Fitogénicos/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias de la Mama/patología , Quimioterapia Adyuvante , Ciclofosfamida/administración & dosificación , Doxorrubicina/administración & dosificación , Femenino , Fluorouracilo/administración & dosificación , Humanos , Persona de Mediana Edad , Neutropenia/inducido químicamente , Paclitaxel/administración & dosificación , Paclitaxel/efectos adversos , Estudios Prospectivos
15.
Ann Surg ; 230(1): 72-8, 1999 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-10400039

RESUMEN

OBJECTIVE: To determine the incidence and prognostic significance of documented eradication of breast cancer axillary lymph node (ALN) metastases after neoadjuvant chemotherapy. SUMMARY BACKGROUND DATA: Neoadjuvant chemotherapy is the standard of care for patients with locally advanced breast cancer and is being evaluated in patients with earlier-stage operable disease. METHODS: One hundred ninety-one patients with locally advanced breast cancer and cytologically documented ALN metastases were treated in two prospective trials of doxorubicin-based neoadjuvant chemotherapy. Patients had breast surgery with level I and II axillary dissection followed by additional chemotherapy and radiation treatment. Nodal sections from 43 patients who were originally identified as having negative ALNs at surgery were reevaluated and histologically confirmed to be without metastases. An additional 1112 sections from these lymph node blocks were obtained; half were stained with an anticytokeratin antibody cocktail and analyzed. Survival was calculated using the Kaplan-Meier method. RESULTS: Of 191 patients with positive ALNs at diagnosis, 23% (43 patients) were converted to a negative axillary nodal status on histologic examination (median number of nodes removed = 16). Of the 43 patients with complete axillary conversion, 26% (n = 11) had N1 disease and 74% (n = 32) had N2 disease. On univariate analysis, patients with complete versus incomplete histologic axillary conversion were more likely to have initial estrogen-receptor-negative tumors, smaller primary tumors, and a complete pathologic response in the primary tumor. The 5-year disease-free survival rates were 87% in patients with preoperative eradication of axillary metastases and 51% for patients with residual nodal disease after neoadjuvant chemotherapy. Of the 39 patients with complete histologic conversion for whom nodal blocks were available, occult nodal metastases were found in additional nodal sections in 4 patients (10%). At a median follow-up of 61 months, the 5-year disease-free survival rates were 87% in patients without occult nodal metastases and 75% in patients with occult nodal metastases. CONCLUSIONS: Neoadjuvant chemotherapy can completely clear the axilla of microscopic disease before surgery, and occult metastases are found in only 10% of patients with a histologically negative axilla. The results of this study have implications for the potential use of sentinel lymph node biopsy as an alternative to axillary dissection in patients treated with neoadjuvant chemotherapy.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Antimetabolitos Antineoplásicos/administración & dosificación , Antineoplásicos/administración & dosificación , Antineoplásicos Alquilantes/administración & dosificación , Axila , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/cirugía , Quimioterapia Adyuvante , Ciclofosfamida/administración & dosificación , Doxorrubicina/administración & dosificación , Fluorouracilo/administración & dosificación , Humanos , Incidencia , Metástasis Linfática , Persona de Mediana Edad , Terapia Neoadyuvante , Cuidados Preoperatorios , Pronóstico , Estudios Prospectivos , Tasa de Supervivencia
16.
Cancer Chemother Pharmacol ; 43(6): 471-8, 1999.
Artículo en Inglés | MEDLINE | ID: mdl-10321507

RESUMEN

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.


Asunto(s)
Antibióticos Antineoplásicos/efectos adversos , Neoplasias de la Mama/tratamiento farmacológico , Doxorrubicina/efectos adversos , Insuficiencia Cardíaca/inducido químicamente , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Metástasis de la Neoplasia , Estudios Retrospectivos
17.
J Clin Oncol ; 17(3): 846-54, 1999 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-10071275

RESUMEN

PURPOSE: To assess whether pamidronate can reduce the frequency of skeletal morbidity in women with lytic bone metastases from breast cancer treated with hormone therapy. PATIENTS AND METHODS: Three hundred seventy-two women with breast cancer who had at least one lytic bone lesion and who were receiving hormonal therapy were randomized to receive 90 mg of pamidronate or placebo as a 2-hour intravenous infusion given in double-blind fashion every 4 weeks for 24 cycles. Patients were evaluated for skeletal complications: pathologic fractures, spinal cord compression, irradiation of or surgery on bone, or hypercalcemia. The skeletal morbidity rate (the ratio of the number of skeletal complications to the time on trial) was the primary efficacy variable. Bone pain, use of analgesics, quality of life, performance status, bone tumor response, and biochemical parameters were also evaluated. RESULTS: One hundred eighty-two patients who received pamidronate and 189 who received placebo were assessable. The skeletal morbidity rate was significantly reduced at 12, 18, and 24 cycles in patients treated with 90 mg of pamidronate (P = .028, .023, and .008, respectively). At 24 cycles, the proportion of patients having had any skeletal complication was 56% in the pamidronate group and 67% in the placebo group (P = .027). The time to the first skeletal complication was longer for patients receiving pamidronate than for those given placebo (P = .049). There was no statistical difference in survival or in objective bone response rate. Pamidronate was well tolerated. CONCLUSION: Treatment with 90 mg of pamidronate as a 2-hour intravenous infusion every 4 weeks in addition to hormonal therapy significantly reduces skeletal morbidity from osteolytic metastases.


Asunto(s)
Antineoplásicos/uso terapéutico , Enfermedades Óseas/tratamiento farmacológico , Neoplasias de la Mama/tratamiento farmacológico , Difosfonatos/uso terapéutico , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Enfermedades Óseas/complicaciones , Enfermedades Óseas/patología , Neoplasias de la Mama/complicaciones , Quimioterapia Adyuvante , Difosfonatos/administración & dosificación , Método Doble Ciego , Femenino , Humanos , Hipercalcemia/complicaciones , Megestrol/administración & dosificación , Persona de Mediana Edad , Metástasis de la Neoplasia , Pamidronato , Tamoxifeno/administración & dosificación
18.
Cancer Invest ; 16(1): 6-11, 1998.
Artículo en Inglés | MEDLINE | ID: mdl-9474245

RESUMEN

The objective of this cross-sectional study was to determine lumbar spine bone mineral density (BMD) in breast cancer patients previously treated with adjuvant chemotherapy. Sixteen of 27 patients who received adjuvant chemotherapy became permanently amenorrheic as a result of chemotherapy. BMD was measured at the lumbar spine using dual energy X-ray absorptiometry (DEXA). Chemotherapy drugs and dosages along with a history of risk factors for reduced bone density including activity level, tobacco and/or alcohol use, metabolic bone disease, family history, and hormone exposure were identified. Results showed that women who became permanently amenorrheic as a result of chemotherapy had BMD 14% lower than women who maintained menses after chemotherapy. Chemotherapy-treated women who maintained ovarian function had normal BMD. This study suggests that women who have premature menopause as a result of chemotherapy for breast cancer are at increased risk of bone loss and may be at risk for early development of osteoporosis. Women who maintain menses do not appear to be at risk for accelerated trabecular bone loss.


Asunto(s)
Neoplasias de la Mama/tratamiento farmacológico , Adulto , Factores de Edad , Densidad Ósea , Neoplasias de la Mama/patología , Calcio/metabolismo , Ciclofosfamida/administración & dosificación , Dieta , Femenino , Humanos , Menopausia , Persona de Mediana Edad , Osteoporosis/genética , Aptitud Física , Proyectos Piloto
19.
J Clin Oncol ; 16(1): 348-53, 1998 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-9440763

RESUMEN

PURPOSE: Tamoxifen is currently the standard hormonal treatment of breast cancer, both for metastatic disease and in the adjuvant setting. A new antiestrogen, toremifene, was approved recently for use in managing metastatic breast cancer in postmenopausal women. METHODS: Toremifene is structurally similar to tamoxifen, differing only by a single chlorine atom, and has a similar pharmacologic profile. The major difference between the two compounds is in the preclinical activity; chronic, high-dose tamoxifen is hepatocarcinogenic in the rat, whereas toremifene is not. Neither agent is hepatocarcinogenic in mice, hamsters, or humans; therefore, clinical relevance of the rat data may not be significant. RESULTS: In a worldwide phase III trial, the two agents demonstrated comparable efficacy and safety against metastatic breast cancer. Both agents have shown a significant hypocholesterolemic effect after long-term administration. CONCLUSION: Due to the paucity of long-term clinical data on toremifene, important unresolved questions remain, which include its effects on bone mineral density, the frequency of cardiac events, and the risk for endometrial cancer. Tamoxifen has been associated with maintenance of bone mineral density, a reduction in cardiac events, and a slightly increased risk of endometrial cancer. Toremifene is not likely to be used as second-line therapy after tamoxifen failure due to cross-resistance, and its ultimate place in therapy of advanced breast cancer remains to be determined.


Asunto(s)
Antineoplásicos Hormonales/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Tamoxifeno/uso terapéutico , Animales , Antineoplásicos Hormonales/efectos adversos , Antineoplásicos Hormonales/metabolismo , Cricetinae , Aductos de ADN/metabolismo , Resistencia a Antineoplásicos , Femenino , Humanos , Lípidos/sangre , Neoplasias Mamarias Experimentales/inducido químicamente , Ratones , Ratas , Tamoxifeno/efectos adversos , Tamoxifeno/metabolismo , Toremifeno/efectos adversos , Toremifeno/metabolismo , Toremifeno/uso terapéutico
20.
In Vivo ; 12(6): 659-65, 1998.
Artículo en Inglés | MEDLINE | ID: mdl-9891229

RESUMEN

Chemoprevention of breast cancer has long been an attractive goal. However, the women most likely to benefit from chemoprevention, women at high risk for breast cancer, have traditionally been difficult to identify. The increased incidence of proliferative breast disease (PBD), associated with an increased risk of developing breast cancer and the identification of the BRCA1 and BRCA2 breast cancer susceptibility genes have provided the opportunity for identification of high risk women. Recent chemopreventive randomized clinical trials have demonstrated that antiestrogens, in particular tamoxifen, and retinoids are among the most effective chemopreventive agents. Adjuvant dietary modifications have also been considered for investigation based on epidemiological and preclinical observations that links high-fat diet to mammary tumorigenesis. In future clinical trials, monitoring of molecular markers of genetic instability through novel laboratory techniques will provide sensitive surrogate endpoint biomarkers (SBEs) to evaluate efficacy of chemopreventive interventions.


Asunto(s)
Neoplasias de la Mama/prevención & control , Quimioprevención , Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/tratamiento farmacológico , Dietoterapia , Antagonistas de Estrógenos/uso terapéutico , Femenino , Humanos , Retinoides/uso terapéutico , Medición de Riesgo
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