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1.
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
2.
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
3.
Int J Cancer ; 73(2): 184-6, 1997 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-9335439

RESUMEN

We tested the efficacy of nifedipine to reverse acquired resistance to chemotherapy regimens containing doxorubicin or vinblastine or both in 12 patients with metastatic breast cancer. All patients had been receiving one or both of these drugs, had had a prior partial response (median duration 5 months, range 2-10) and subsequently progressed. Immediately after drug resistance was documented by tumor progression, eligible patients with measurable or evaluable disease were treated with nifedipine beginning 3 days before restarting the same chemotherapy. The initial dose of nifedipine was 20 mg TID, escalating daily to 40 mg TID on day 3 if the patient had no serious side effects. Nifedipine was continued at the highest tolerable dose during and for 2 days after completion of the chemotherapy. Most patients had < or = 2 prior chemotherapy regimens and a median Zubrod performance status of 1. Twelve patients received a total of 23 courses preceded by nifedipine. No objective tumor responses were observed. The expected toxic effects attributable to nifedipine occurred, but nifedipine did not increase the toxicity caused by the chemotherapy. Nifedipine, given in this dose and schedule, did not reverse acquired drug resistance in patients with breast cancer.


Asunto(s)
Neoplasias de la Mama/tratamiento farmacológico , Bloqueadores de los Canales de Calcio/uso terapéutico , Nifedipino/uso terapéutico , Administración Oral , Adulto , Anciano , Antibióticos Antineoplásicos/uso terapéutico , Antineoplásicos Fitogénicos/uso terapéutico , Neoplasias de la Mama/secundario , Bloqueadores de los Canales de Calcio/efectos adversos , Doxorrubicina/uso terapéutico , Resistencia a Antineoplásicos , Quimioterapia Combinada , Femenino , Humanos , Persona de Mediana Edad , Nifedipino/efectos adversos , Vinblastina/uso terapéutico
4.
Semin Oncol ; 23(5 Suppl 11): 46-56, 1996 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-8893900

RESUMEN

Combinations of active antineoplastic agents have been the most effective treatment for metastatic breast cancer. Criteria for an effective combination include use of drugs with different mechanisms of action, nonoverlapping toxic effects, and synergistic, or at least additive, antitumor activity. Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ), with its unique mechanism of action, offers an excellent opportunity for development of effective combination therapy against breast cancer. However, a number of problems have hindered the rapid development of effective combinations. The most obvious problem is the lack of a defined optimal dose and schedule of administration. The second problem has been the demonstration of unexpected interactions between paclitaxel and the other component(s) of the combination, often resulting in unusual and serious toxic effects. This review will focus on the phase I and II trials of paclitaxel in combination with established antineoplastic drugs (except doxorubicin and congeners, which is covered elsewhere in this issue) for breast cancer: cisplatin, 5-fluorouracil with or without folinic acid, cyclophosphamide, radiation therapy, as well as novel investigational agents or strategies, edatrexate, monoclonal antibodies to oncogenes, growth factors, and gene therapy with insertion of multidrug resistance gene into blood stem cells. Combination therapy offers exciting possibilities of enhanced antitumor efficacy. However, given the unexpected and serious toxic effects observed, only proven combinations should be used outside the context of a clinical trial. Additionally, the burden of proof will be to show that these combinations have increased antitumor activity, decreased toxicity, or both compared with single-agent paclitaxel.


Asunto(s)
Antineoplásicos Fitogénicos/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Paclitaxel/administración & dosificación , Aminopterina/administración & dosificación , Aminopterina/análogos & derivados , Antibióticos Antineoplásicos/administración & dosificación , Antibióticos Antineoplásicos/efectos adversos , Antibióticos Antineoplásicos/farmacología , Anticuerpos Monoclonales/uso terapéutico , Antídotos/administración & dosificación , Antimetabolitos Antineoplásicos/administración & dosificación , Antineoplásicos/administración & dosificación , Antineoplásicos Alquilantes/administración & dosificación , Antineoplásicos Fitogénicos/efectos adversos , Antineoplásicos Fitogénicos/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Cisplatino/administración & dosificación , Ensayos Clínicos Fase I como Asunto , Ensayos Clínicos Fase II como Asunto , Ciclofosfamida/administración & dosificación , Doxorrubicina/administración & dosificación , Doxorrubicina/efectos adversos , Doxorrubicina/farmacología , Esquema de Medicación , Sinergismo Farmacológico , Drogas en Investigación/administración & dosificación , Femenino , Fluorouracilo/administración & dosificación , Terapia Genética , Humanos , Leucovorina/administración & dosificación , Metástasis de la Neoplasia , Oncogenes , Paclitaxel/efectos adversos , Paclitaxel/farmacología , Radioterapia Adyuvante
5.
Semin Oncol ; 23(5 Suppl 12): 29-39, 1996 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-8941408

RESUMEN

After the single-agent activity of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) was confirmed, trials to develop a synergistic combination began. Doxorubicin, the most active agent for breast cancer, was studied first. As paclitaxel became more available, other combinations, including high-dose regimens and adjuvant therapies, have been studied. No optimal combination regimen has been defined. Recent and/or ongoing trials are looking at paclitaxel in combination with cisplatin, cyclophosphamide, 5-fluorouracil/ folinic acid, and mitoxantrone combinations, as well as with high-dose regimens and as adjuvant therapy. This review describes a plethora of combination studies finally under way to better define the optimal use of paclitaxel in breast cancer therapies, both as adjuvant treatment and for metastatic disease. Because of the unpredictable nature of drug interactions related to schedule and sequence, ad hoc combinations should not be undertaken outside the context of a well-designed trial.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Paclitaxel/administración & dosificación , Aminopterina/administración & dosificación , Aminopterina/análogos & derivados , Neoplasias de la Mama/patología , Quimioterapia Adyuvante , Cisplatino/administración & dosificación , Ensayos Clínicos como Asunto , Doxorrubicina/administración & dosificación , Interacciones Farmacológicas , Sinergismo Farmacológico , Epirrubicina/administración & dosificación , Fluorouracilo/administración & dosificación , Humanos , Ifosfamida/administración & dosificación , Metástasis de la Neoplasia
6.
Cancer ; 65(3): 394-9, 1990 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-2297630

RESUMEN

To evaluate the role of chemotherapy in local control of primary breast cancer, the incidence of local failure was evaluated in 768 patients treated with surgery and adjuvant, combination chemotherapy that contained fluorouracil, doxorubicin, and cyclophosphamide (FAC) at our institute between 1974 and 1982. Of these patients, 429 received postoperative irradiation (XRT) before adjuvant therapy. A group of 178 historical control patients had mastectomies and received irradiation after surgery without chemotherapy. The rates of locoregional recurrence alone in the three groups were as follows: FAC, 12%; FAC plus XRT, 5%; and XRT, 10%. The difference in recurrence rates between the FAC group and the FAC plus XRT subgroup was significant (P less than 0.01). Local failure rates were evaluated by stage and nodal status; patients with Stage III disease and those with four or more disease-positive nodes had a higher incidence of local failure than did patients with Stage II disease or those who had one to three positive nodes. Systemic chemotherapy and local therapies resulted in 50% local control at the time of locoregional recurrence in patients treated with FAC, whereas local control was achieved in 18% of patients with local recurrence in the XRT subgroups. Overall life-time local control of disease was similar whether irradiation was administered initially (in the period after operation) or at the time of local recurrence. Irradiation after mastectomy remains an integral part of a combined modality approach in selected groups of patients.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/terapia , Neoplasias de la Mama/patología , Terapia Combinada , Ciclofosfamida/administración & dosificación , Doxorrubicina/administración & dosificación , Femenino , Fluorouracilo/administración & dosificación , Humanos , Mastectomía/métodos , Recurrencia Local de Neoplasia/prevención & control , Estadificación de Neoplasias , Estudios Retrospectivos
7.
Cancer Chemother Pharmacol ; 27(2): 94-100, 1990.
Artículo en Inglés | MEDLINE | ID: mdl-2249339

RESUMEN

A total of 106 patients with inflammatory carcinoma of the breast underwent combined-modality treatment consisting of doxorubicin-containing chemotherapy. All patients received three cycles of 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC) before local therapy. From 1974 to 1977 (group A), primary radiotherapy was the local treatment modality and chemotherapy was given for a total of 24 months. From 1978 to 1981 (group B), mastectomy became the primary local treatment modality and FAC was reinstituted within 10-14 days after surgery; after completion of FAC, consolidation radiotherapy was given. From 1982 to 1986 (group C), vincristine and prednisone were added to FAC, and doxorubicin was given by continuous infusion. The median follow-up of the three groups was 56 months. For patients alive at the time of analysis, median follow-ups were 141, 111, and 49 months in groups A, B, and C, respectively. Disease-free survival at 5 years was 35%, 22%, and 41% for groups A, B, and C, respectively, and respective overall survival at 5 years was 37%, 30%, and 48%. Mastectomy in addition to radiotherapy resulted in local control rates similar to those obtained with radiotherapy alone, but this approach would result in fewer late sequelae of high-dose irradiation and provided histologic staging for chemotherapy response. The patients treated on protocol C had slightly better disease-free and overall survival, but the differences were not statistically significant. The 5-year disease-free survival of patients achieving a clinical complete remission (CR) or partial remission (PR) was superior to that of patients whose response was less than a PR. There was no episode of doxorubicin-related cardiac toxicity in group C. Combined-modality treatment for inflammatory carcinoma of the breast resulted in improved survival.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Carcinoma/tratamiento farmacológico , Adulto , Anciano , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/radioterapia , Neoplasias de la Mama/cirugía , Carcinoma/mortalidad , Carcinoma/radioterapia , Carcinoma/cirugía , Terapia Combinada , Ciclofosfamida/administración & dosificación , Ciclofosfamida/uso terapéutico , Doxorrubicina/administración & dosificación , Doxorrubicina/uso terapéutico , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/uso terapéutico , Humanos , Mastectomía , Persona de Mediana Edad , Prednisona/administración & dosificación , Pronóstico , Inducción de Remisión , Vincristina/administración & dosificación
8.
Invest New Drugs ; 7(2-3): 225-9, 1989 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-2793377

RESUMEN

We evaluated the role of gallium nitrate infusion in the treatment of metastatic breast cancer. Gallium nitrate was administered at 300 mg/m2/day for 7 days every 3 weeks by continuous infusion concomitantly with oral calcium supplement of 500 mg twice daily and oral hydration. Fifteen patients with refractory metastatic breast cancer received such treatment for a total of 30 courses. Median age was 51, and median performance status (Zubrod scale) was 1. These patients had minimal prior chemotherapy (median 1 regimen). All patients were evaluable for toxicity and 14 for response. Nine patients had one to two metastatic sites, five patients had three to four sites. No major objective response was seen, but one patient had a minor response (10 weeks), and another showed no change in disease (16 weeks). Diverse low-grade toxicities were observed, including nausea and vomiting in 11 patients, anorexia in 11, diarrhea in eight, stomatitis in five, dysgeusia in six, musculoskeletal pain in five, skin rash in seven, partially reversible tinnitus and/or mild hearing loss in four and sensory neuropathy in two. A consistent drop in hemoglobin (median of 3.2 g/dL per patient) necessitated blood transfusion in seven patients. There was no granulocytopenia or thrombocytopenia; however, significant lymphopenia was noted. Reversible, moderate nephrotoxicity occurred in two patients. The hypocalcemic effect was consistent, with a median drop in serum calcium of 1.25 mg/dL per course. There was no hepatic toxicity. While no single toxicity was severe, overall toxicity adversely influenced treatment tolerance. Gallium nitrate by continuous infusion, as given in this study, has no activity in metastatic breast cancer.


Asunto(s)
Neoplasias de la Mama/tratamiento farmacológico , Galio/uso terapéutico , Adulto , Anciano , Evaluación de Medicamentos , Recuento de Eritrocitos , Femenino , Galio/administración & dosificación , Galio/efectos adversos , Hemoglobinas/metabolismo , Humanos , Infusiones Intravenosas , Persona de Mediana Edad
9.
Cancer ; 62(12): 2507-16, 1988 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-3056604

RESUMEN

One hundred seventy-four evaluable patients with noninflammatory Stage III (both operable and inoperable) breast cancer were treated with a combined modality strategy between 1974 and 1985. All patients received combination chemotherapy with 5-fluorouracil, Adriamycin (doxorubicin), and cyclophosphamide (FAC) as their initial form of therapy. After three cycles of chemotherapy, local treatment in the form of a total mastectomy with axillary dissection, or radiotherapy, or both, was completed. Subsequently, adjuvant chemotherapy was continued. There were 48 patients with Stage IIIA, and 126 patients with Stage IIIB disease. A complete remission was achieved in 16.7% of the patients, and 70.7% achieved a partial remission after the initial three cycles of FAC. The complete response rate was higher for patients with Stage IIIA, than for patients with Stage IIIB disease. All but six of the 174 patients treated were rendered disease-free after induction chemotherapy and local treatment. The median follow-up of this group of patients is 59 months. The 5-year disease-free survival rates were 84% for patients with Stage IIIA, and 33% for patients with Stage IIIB disease. The 5-year survival rate for, patients with Stage IIIA was 84%, and for patients with Stage IIIB 44%. At 10 years, 56% of patients with Stage IIIA and 26% of patients with Stage IIIB disease are projected to be alive. Younger patients, and those with estrogen receptor-positive tumors, had a trend for better survival than older patients and those with estrogen receptor-negative tumors. The quality of response to induction chemotherapy correlated prominently with prognosis, as did compliance with treatment. Twenty-six patients (15.3%) had locoregional recurrence. This multidisciplinary approach to locally advanced breast cancer rendered most patients disease-free and produced an excellent local control rate. Modifications of this treatment strategy may result in further improvement of survival rates.


Asunto(s)
Neoplasias de la Mama/terapia , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Terapia Combinada , Ciclofosfamida/administración & dosificación , Doxorrubicina/administración & dosificación , Fluorouracilo/administración & dosificación , Humanos , Metástasis Linfática , Mastectomía Radical Modificada , Mastectomía Simple , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Receptores de Estrógenos/análisis
10.
Cancer ; 62(10): 2098-104, 1988 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-3179922

RESUMEN

Three hundred ten patients with Stage II or Stage III breast cancer were entered on an adjuvant protocol consisting of a combination of 5-fluorouracil, doxorubicin, cyclophosphamide, vincristine, and prednisone (FACVP). In the second phase of the study, patients with estrogen receptor-negative tumors received sequential courses of methotrexate and vinblastine. Other patients, who were estrogen receptor-positive or unknown, were randomized to receive either tamoxifen alone or tamoxifen plus methotrexate and vinblastine. All therapy was completed within 1 year. The estimated disease-free rate at 5 years was 68% among patients with Stage II disease and 52% for patients who had Stage III disease. Among patients with estrogen receptor-positive tumors, disease-free survival was significantly prolonged in patients who received methotrexate and vinblastine in addition to tamoxifen (P = 0.04). However, this difference was less pronounced when all randomized patients (including those whose estrogen receptor status was unknown) were included in the comparison. Although most patients experienced moderate to severe granulocytopenia, infectious complications were infrequent. One patient died of septicemia. Congestive heart failure developed in two patients, one of whom had a history of myocardial infarction and congestive heart failure.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias de la Mama/radioterapia , Neoplasias de la Mama/cirugía , Terapia Combinada , Ciclofosfamida/administración & dosificación , Doxorrubicina/administración & dosificación , Femenino , Fluorouracilo/administración & dosificación , Estudios de Seguimiento , Humanos , Metástasis Linfática , Menopausia , Persona de Mediana Edad , Estadificación de Neoplasias , Prednisona/administración & dosificación , Receptores de Estrógenos/análisis , Vincristina/administración & dosificación
12.
JAMA ; 256(21): 2988-90, 1986 Dec 05.
Artículo en Inglés | MEDLINE | ID: mdl-3773217

RESUMEN

We evaluated serial liver function tests (LFT) and serial liver imaging procedures for 190 consecutive patients with breast carcinoma to assess the incidence and severity of hepatic abnormalities during treatment with combination chemotherapy. Thirty-four percent of patients receiving adjuvant chemotherapy and 52% of patients being treated for metastatic breast cancer had one or more LFT abnormalities before initiation of therapy. Among patients with normal baseline LFT results, 77% of those receiving adjuvant chemotherapy and 82% being treated for metastatic breast cancer developed LFT abnormalities during therapy. Liver function test abnormalities were mild to moderate and never led to interruption of treatment; they appeared within the first three months of chemotherapy and normalized in 90% within one year of cessation of treatment. Our analysis suggests that LFT abnormalities detected during the administration of chemotherapy for patients with breast cancer are a manifestation of drug toxicity and that such abnormalities are insufficient evidence of hepatic metastases.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias de la Mama/tratamiento farmacológico , Pruebas de Función Hepática , Hígado/efectos de los fármacos , Fosfatasa Alcalina/sangre , Aspartato Aminotransferasas/sangre , Proteínas Sanguíneas/metabolismo , Neoplasias de la Mama/sangre , Ciclofosfamida/administración & dosificación , Doxorrubicina/administración & dosificación , Fluorouracilo/administración & dosificación , Humanos , L-Lactato Deshidrogenasa/sangre , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/secundario
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