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1.
J Clin Oncol ; 9(11): 1967-72, 1991 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-1941055

RESUMO

In a previous study (J Clin Oncol 7:1407-1417, 1989), we identified two dosage administration schedules of fluorouracil (5FU) combined with leucovorin that were superior to single-agent 5FU for the treatment of advanced colorectal cancer. In this same study, a regimen of 5FU plus high-dose methotrexate (MTX) demonstrated a suggestive advantage over 5FU alone. To permit a more definitive comparison, we have extended our evaluation of these three regimens to involve an additional 259 patients. In all, 457 patients with advanced colorectal cancer were randomly assigned to one of the following regimens: 5FU plus low-dose leucovorin, 5FU plus high-dose leucovorin, or 5FU plus high-dose MTX with leucovorin rescue. We have found that each of the 5FU/leucovorin regimens demonstrates a significant (P less than or equal to .01) advantage over 5FU plus high-dose MTX for objective tumor response and interval to tumor progression. Moreover, 5FU plus low-dose leucovorin confers a significant survival benefit (P less than or equal to .01) compared with 5FU plus high-dose MTX. The 5FU plus high-dose leucovorin regimen shows a survival benefit only in unadjusted analyses (P = .04), but this difference is not significant when adjusted for imbalances in prognostic variables (P = .44). Evaluation of the two 5FU/leucovorin regimens rules out a 10% decrease in death rate for the high-dose leucovorin regimen compared with the low-dose leucovorin regimen (P less than .05). The regimen of 5FU plus low-dose leucovorin has now been shown to offer a statistically significant survival advantage versus 5FU alone and versus 5FU plus high-dose MTX, a regimen that had shown promise in earlier trials. These data confirm the efficacy of leucovorin combined with 5FU in patients with advanced colorectal cancer and establish that it is not necessary to use high doses of leucovorin to achieve these results.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Colorretais/patologia , Feminino , Fluoruracila/administração & dosagem , Humanos , Leucovorina/administração & dosagem , Masculino , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Análise de Sobrevida
2.
J Clin Oncol ; 5(10): 1534-45, 1987 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-3655856

RESUMO

In a prospective, randomized trial Cancer and Leukemia Group B (CALGB) evaluated CAF chemotherapy (cyclophosphamide + doxorubicin + 5-fluorouracil [5-FU]) v CAF plus tamoxifen (TCAF) in advanced breast cancer. Patients were stratified by estrogen receptor (ER) status, dominant site of metastatic disease, menopausal status, and prior adjuvant therapy. Regardless of ER status or menopausal status, the addition of tamoxifen conferred no significant advantage in response rate, response duration, time to treatment failure (TTF) or survival over CAF alone. A secondary objective was to compare the response to CAF of ER positive (ER+) and ER negative (ER-) patients to determine if there was a differential response to cytotoxic chemotherapy. Response rates of ER+ and ER- patients to CAF were identical (56%), but the response duration, time to treatment failure, and survival of ER+ patients were significantly longer than ER- patients. This lack of differential response implies that chemotherapy and hormonal therapy may compete for the same pool of ER+ cells. It also suggests that chemotherapy kills breast cancer cells indiscriminately, regardless of ER status.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Feminino , Fluoruracila/administração & dosagem , Humanos , Menopausa , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Prospectivos , Distribuição Aleatória , Receptores de Estrogênio/análise , Tamoxifeno/administração & dosagem
3.
J Clin Oncol ; 8(9): 1483-96, 1990 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-2202791

RESUMO

The National Surgical Adjuvant Breast and Bowel Project (NSABP) implemented protocol B-15 to compare 2 months of Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH) and cyclophosphamide (AC) with 6 months of conventional cyclophosphamide, methotrexate, and fluorouracil (CMF) in patients with breast cancer nonresponsive to tamoxifen (TAM, T). A second aim was to determine whether AC followed in 6 months by intravenous (IV) CMF was more effective than AC without reinduction therapy. Through 3 years of follow-up, findings from 2,194 patients indicate no significant difference in disease-free survival (DFS, P = .5), distant disease-free survival (DDFS, P = .5) or survival (S, P = .8) among the three groups. Since the outcome from AC and CMF was almost identical, the issue arises concerning which regimen is more appropriate for the treatment of breast cancer patients. AC seems preferable since, following total mastectomy, AC was completed on day 63 versus day 154 for conventional CMF; patients visited health professionals three times as often for conventional CMF as for AC; women on AC received therapy on each of 4 days versus on each of 84 days for conventional CMF; and nausea-control medication was given for about 84 days to conventional CMF patients versus for about 12 days to patients on AC. The difference in the amount of alopecia between the two treatment groups was less than anticipated. While alopecia was almost universally observed following AC therapy, 71% of the CMF patients also had hair loss and, in 41%, the loss was greater than 50%. This study and NSABP B-16, which evaluates the worth of AC therapy in TAM-responsive patients, indicate the merit of 2 months of AC therapy for all positive-node breast cancer patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Tamoxifeno/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/cirurgia , Terapia Combinada , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Relação Dose-Resposta a Droga , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , Metotrexato/administração & dosagem , Metotrexato/efeitos adversos , Pessoa de Meia-Idade , Prognóstico , Ensaios Clínicos Controlados Aleatórios como Assunto , Análise de Sobrevida
4.
J Clin Oncol ; 12(11): 2321-6, 1994 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-7964947

RESUMO

PURPOSE: We evaluated the effect of recombinant interferon gamma (rIFN-gamma) on survival and toxicity in small-cell lung cancer (SCLC) patients in complete remission (CR). PATIENTS AND METHODS: One hundred patients in CR following treatment with six cycles of combination chemotherapy, thoracic radiotherapy (TRT), and prophylactic cranial irradiation (PCI) were studied. All patients had been enrolled onto a cooperative group trial (North Central Cancer Treatment Group [NCCTG] 86-20-51). Patients received observation only or rIFN-gamma at a dose of 4 x 10(6) U subcutaneously per day for 6 months. RESULTS: Six patients (12%) did not comply with rIFN-gamma treatment. Substantial nonhematologic toxicities consisting of chills, myalgia, lethargy, and alteration of mood-personality were observed. No patient experienced life-threatening or fatal toxicity. The median times to progression for rIFN-gamma treatment or observation were 6.9 and 8.1 months (P = .54). The median survival times were 13.3 and 18.8 months, respectively (P = .43). Approximately 70% of all patients relapsed within 2 years. CONCLUSION: Time to progression and survival were inferior in patients treated with rIFN-gamma compared with randomized control subjects, although this difference was not statistically significant. These data indicate that rIFN-gamma treatment is not associated with a 33% improvement in survival (P = .04). Because of the high rate of relapse, SCLC patients in CR are an ideal group in which to evaluate novel and minimally toxic agents.


Assuntos
Carcinoma de Células Pequenas/terapia , Interferon gama/efeitos adversos , Neoplasias Pulmonares/terapia , Adulto , Idoso , Transtornos Plaquetários/etiologia , Carcinoma de Células Pequenas/mortalidade , Terapia Combinada , Relação Dose-Resposta a Droga , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Cooperação do Paciente , Contagem de Plaquetas , Proteínas Recombinantes , Indução de Remissão , Análise de Sobrevida
5.
J Clin Oncol ; 12(1): 70-6, 1994 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-8270988

RESUMO

PURPOSE: The combination of etoposide (E) and cisplatin (P) is an accepted standard therapy for small-cell lung cancer (SCLC); however, the optimal sequencing and administration schedule has not been defined. This study was designed to evaluate different sequencing and administration schedules of E and P in the treatment of SCLC. PATIENTS AND METHODS: Five hundred fifty-two eligible patients with limited-(LD) and extensive-stage (ED) SCLC were randomized to receive one of the following regimens: arm A, P 30 mg/m2 by intravenous (IV) bolus followed by E 130 mg/m2 bolus; arm B, E 130 mg/m2 bolus followed by P 30 mg/m2 bolus; arm C, E 130 mg/m2 by 24-hour infusion and P 30 mg/m2 bolus at the end of each 24-hour infusion of E; arm D, E 130 mg/m2 by 24-hour infusion and P 45 mg/m2 by 24-hour infusion on day 2 and 3 only. Two 3-day induction cycles of IV EP were administered 4 weeks apart. Subsequent therapy was the same for all arms, consisting of four cycles of cyclophosphamide, doxorubicin, and vincristine (CAV) at 4-week intervals. Consolidative thoracic radiation therapy (TRT) and prophylactic cranial irradiation (PCI) were administered to responders. RESULTS: The overall response rate (84%) was similar in all treatment arms. Treatment arm A was associated with the best complete response (CR) rate (52%), the most favorable median survival time (MST) of 15 months, and a 26% 2-year survival rate. Patients with LD on arm A had a MST of 20 months and a 42% 2-year survival rate. Multivariate analysis indicated that extent of disease, performance status, arm of therapy, and sex were significant independent factors influencing survival. Toxicity of the four regimens was similar, except for greater thrombocytopenia on arm D. CONCLUSION: The bolus administration of EP with E following P for the first two cycles of chemotherapy was the most effective regimen, with especially encouraging survival for LD patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma de Células Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Análise Atuarial , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cisplatino/administração & dosagem , Esquema de Medicação , Etoposídeo/administração & dosagem , Feminino , Humanos , Infusões Intravenosas , Injeções Intravenosas , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Prospectivos , Análise de Sobrevida , Resultado do Tratamento
6.
J Clin Oncol ; 12(1): 14-20, 1994 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-7677801

RESUMO

PURPOSE: To compare two commonly used schedules of fluorouracil (5FU) and leucovorin in the treatment of patients with advanced metastatic colorectal cancer. Each of these dosage administration schedules has been demonstrated to be superior to single-agent bolus 5FU in previous controlled trials. PATIENTS AND METHODS: Three hundred seventy-two ambulatory patients with metastatic colorectal cancer were stratified according to performance status, and presence and location of any measurable indicator lesion(s). They were then randomized to receive chemotherapy with one of the following regimens: (1) intensive-course 5FU plus low-dose leucovorin (5FU 425 mg/m2 plus leucovorin 20 mg/m2 intravenous [IV] push daily for 5 days with courses repeated at 4- to 5-week intervals); (2) weekly 5FU plus high-dose leucovorin (5FU 600 mg/m2 IV push plus leucovorin 500 mg/m2 as a 2-hour infusion weekly for 6 weeks with courses repeated every 8 weeks). RESULTS: Three hundred sixty-two of 372 patients randomized (97.3%) were eligible and included in the analysis. Three hundred forty-six patients (95.6%) have died. There were no significant differences in therapeutic efficacy between the two 5FU/leucovorin regimens tested with respect to the following parameters: objective tumor response (35% v 31%), survival (median, 9.3 v 10.7 months), and palliative effects (as assessed by relief of symptoms, improved performance status, and weight gain). There were significant (P < .05) differences in toxicity, with more leukopenia and stomatitis seen with the intensive-course regimen, and more diarrhea and requirement for hospitalization to manage toxicity with the weekly regimen. Financial cost was also higher with the weekly regimen. CONCLUSION: Intensive-course 5FU plus low-dose leucovorin appears to have a superior therapeutic index compared with weekly 5FU plus high-dose leucovorin using the dosage administration schedules applied in this study based on similar therapeutic effectiveness, but lower financial cost, and less need for hospitalization to manage chemotherapy toxicity.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias Colorretais/tratamento farmacológico , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Colorretais/patologia , Esquema de Medicação , Feminino , Fluoruracila/administração & dosagem , Humanos , Leucovorina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Estatística como Assunto , Análise de Sobrevida , Resultado do Tratamento
7.
J Clin Oncol ; 19(15): 3539-46, 2001 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-11481361

RESUMO

PURPOSE: This article summarizes the third step of a research program to identify variables that supplement the predictive power of the the Eastern Cooperative Oncology Group (ECOG) performance status (PS) for survival. The objective was to produce a simple, practical, stratification factor for phase III oncology clinical trials involving patients with advanced malignant disease. PATIENTS AND METHODS: A questionnaire was administered to 729 patients with metastatic colorectal or lung cancers. Patients provided a Karnofsky index and appetite rating while physicians provided a survival estimate and the ECOG-PS. Scores for each item were categorized as having a positive, neutral, or negative indication for survival. A patient was classified as having a relatively good prognosis if three or more of the four items showed a positive indication, a bad prognosis if three or more items were negative, and an uncertain prognosis otherwise (Good/Bad/Uncertain [GBU] index). RESULTS: The GBU index improved on the prognostic power of a Cox model quartile index and PS alone and increased the accuracy of survival classification estimates by 5% to 10% more than ECOG-PS alone. For patients with PS of 0 or 1, significant survival patterns exist between GBU groups (P=.002 and.0001, respectively). CONCLUSION: The GBU index may be recommended as a supplementary stratification factor for certain future phase III trials in metastatic lung or colorectal cancer where patient heterogeneity is a particular concern. The GBU represents a relatively modest increase to the cost and patient burden of a clinical trial given the additional control that is achieved over the potentially confounding concomitant to the treatment variable.


Assuntos
Neoplasias Colorretais/mortalidade , Neoplasias Pulmonares/mortalidade , Índice de Gravidade de Doença , Idoso , Ensaios Clínicos Fase III como Assunto/métodos , Neoplasias Colorretais/fisiopatologia , Feminino , Humanos , Neoplasias Pulmonares/fisiopatologia , Masculino , Valor Preditivo dos Testes , Prognóstico , Modelos de Riscos Proporcionais , Inquéritos e Questionários , Análise de Sobrevida
8.
J Clin Oncol ; 19(4): 931-42, 2001 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-11181655

RESUMO

PURPOSE: Uncertainty about the relative worth of doxorubicin/cyclophosphamide (AC) and cyclophosphamide/methotrexate/fluorouracil (CMF), as well as doubt about the propriety of giving tamoxifen (TAM) with chemotherapy to patients with estrogen receptor-negative tumors and negative axillary nodes, prompted the National Surgical Adjuvant Breast and Bowel Project to initiate the B-23 study. PATIENTS AND METHODS: Patients (n = 2,008) were randomly assigned to CMF plus placebo, CMF plus TAM, AC plus placebo, or AC plus TAM. Six cycles of CMF were given for 6 months; four cycles of AC were administered for 63 days. TAM was given daily for 5 years. Relapse-free survival (RFS), event-free survival (EFS), and survival (S) were determined by using life-table estimates. Tests for heterogeneity of outcome used log-rank statistics and Cox proportional hazards models to detect differences across all groups and according to chemotherapy and hormonal therapy status. RESULTS: No significant difference in RFS, EFS, or S was observed among the four groups through 5 years (P =.96,.8, and.8, respectively), for those aged < or = 49 years (P =.97,.5, and.9, respectively), or for those aged > or = 50 years (P =.7,.6, and.6, respectively). A comparison between all CMF- and all AC-treated patients demonstrated no significant differences in RFS (87% at 5 years in both groups, P =.9), EFS (83% and 82%, P =.6), or S (89% and 90%, P =.4). There were no significant differences in RFS, EFS, or S between CMF and AC in patients aged < or = 49 or > or = 50 years. No significant difference in any outcome was observed when chemotherapy-treated patients who received placebo were compared with those given TAM. RFS in both groups was 87% (P =.6), 87% in patients aged < or = 49 (P =.9), and 88% and 87%, respectively (P =.4), in those aged > or = 50 years. CONCLUSION: There was no significant difference in the outcome of patients who received AC or CMF. TAM with either regimen resulted in no significant advantage over that achieved from chemotherapy alone.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Receptores de Estrogênio/metabolismo , Tamoxifeno/administração & dosagem , Fatores Etários , Protocolos de Quimioterapia Combinada Antineoplásica , Axila , Neoplasias da Mama/patologia , Cisplatino , Ciclofosfamida/administração & dosagem , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Feminino , Fluoruracila , Humanos , Metástase Linfática , Metotrexato , Pessoa de Meia-Idade , Cooperação do Paciente , Placebos , Análise de Sobrevida
9.
J Clin Oncol ; 17(11): 3374-88, 1999 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-10550131

RESUMO

PURPOSE: In 1989, the National Surgical Adjuvant Breast and Bowel Project initiated the B-22 trial to determine whether intensifying or intensifying and increasing the total dose of cyclophosphamide in a doxorubicin-cyclophosphamide combination would benefit women with primary breast cancer and positive axillary nodes. B-25 was initiated to determine whether further intensifying and increasing the cyclophosphamide dose would yield more favorable results. PATIENTS AND METHODS: Patients (n = 2,548) were randomly assigned to three groups. The dose and intensity of doxorubicin were similar in all groups. Group 1 received four courses, ie, double the dose and intensity of cyclophosphamide given in the B-22 standard therapy group; group 2 received the same dose of cyclophosphamide as in group 1, administered in two courses (intensified); group 3 received double the dose of cyclophosphamide (intensified and increased) given in group 1. All patients received recombinant human granulocyte colony-stimulating factor. Life-table estimates were used to determine disease-free survival (DFS) and overall survival. RESULTS: No significant difference was observed in DFS (P =.20), distant DFS (P =.31), or survival (P =.76) among the three groups. At 5 years, the DFS in groups 1 and 2 (61% v 64%, respectively; P =. 29) was similar to but slightly lower than that in group 3 (61% v 66%, respectively; P = 08). Survival in group 1 was concordant with that in groups 2 (78% v 77%, respectively; P =.71) and 3 (78% v 79%, respectively; P =.86). Grade 4 toxicity was 20%, 34%, and 49% in groups 1, 2, and 3, respectively. Severe infection and septic episodes increased in group 3. The decrease in the amount and intensity of cyclophosphamide and delays in therapy were greatest in courses 3 and 4 in group 3. The incidence of acute myeloid leukemia increased in all groups. CONCLUSION: Because intensifying and increasing cyclophosphamide two or four times that given in standard clinical practice did not substantively improve outcome, such therapy should be reserved for the clinical trial setting.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Ciclofosfamida/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/mortalidade , Neoplasias da Mama/cirurgia , Quimioterapia Adjuvante , Intervalo Livre de Doença , Relação Dose-Resposta a Droga , Doxorrubicina/administração & dosagem , Feminino , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Humanos , Tábuas de Vida , Mastectomia Radical , Pessoa de Meia-Idade , Falha de Tratamento
10.
Arch Intern Med ; 136(3): 305-13, 1976 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-1062970

RESUMO

The Western Cancer Study Group (WCSG) retrospectively reviewed chronic granulocytic leukemia (CGL) diagnosed during 1960 to 1974 from 22 institutions. In 100 cases, patients had positive findings for the Philadelphia chromosome (Ph'+). In 426 cases karyotyping was not done (Ph'?). Ten patients had no Ph' chromosome (Ph'-). The ten Ph'- patients ranged in age from 8 to 85 years and in survival from 1 to more than 125 months. Their small number and heterogeneity precluded statistical analysis, but this notable heterogeneity of the Ph'- group may well be typical. Busulfan prolonged survival in the Ph'+ and Ph'? patients. Females and younger patients tolerated their disease better than males and older patients. Survival studies without reference to the Ph' status, treatment, age at diagnosis, and sex are probably not valid.


Assuntos
Aberrações Cromossômicas , Leucemia Mieloide/mortalidade , Adolescente , Adulto , Fatores Etários , Bussulfano/uso terapêutico , Criança , Feminino , Humanos , Leucemia Mieloide/genética , Leucemia Mieloide/terapia , Masculino , Estudos Retrospectivos , Fatores Sexuais
11.
Arch Intern Med ; 152(4): 837-40, 1992 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-1558443

RESUMO

BACKGROUND: Continuous quality improvement is being advocated as the process that, if adopted, would improve the efficiency, productiveness, and quality of medical institutions, thereby helping to solve the health care crisis our country is facing. To determine if these techniques could be effective in a tertiary-care multispecialty group practice, a model project was undertaken. The model project chosen was to determine if we could improve the turnaround time for "stat" laboratory examinations performed in our large outpatient facility. METHODS: A 10-member team consisting of everyone involved in the process of laboratory testing was empowered to evaluate the present process and make appropriate changes. With traditional techniques of quality improvement, the process was assessed, data were collected and statistically analyzed, changes were introduced, and data were recollected and analyzed. RESULTS: After intervention, the preanalytic delays were reduced by 76% and the postanalytic delays by 88%. Waiting time for patients was reduced by an average of 62%. By instituting the changes suggested, the institution saved $225,000 on a one-time basis and $40,000 to $50,000 on a recurring basis. CONCLUSION: Adoption of quality improvement techniques appears to be a desirable management paradigm that should be explored by all medical institutions interested in maximizing the quality of care offered while at the same time minimizing its cost.


Assuntos
Laboratórios/normas , Garantia da Qualidade dos Cuidados de Saúde/organização & administração , Instituições de Assistência Ambulatorial/organização & administração , Eficiência , Prática de Grupo/organização & administração , Laboratórios/organização & administração , Louisiana , Projetos Piloto , Estudos de Tempo e Movimento
12.
Chest ; 68(2): 265-7, 1975 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-50163

RESUMO

A patient with nodular histiocytic lymphoma was treated with bleomycin; she later developed interstitial pneumonitis documented by lung biopsy. The dose of bleomycin producing this complication was lower than previously reported, and the pulmonary toxicity was apparently completely reversible.


Assuntos
Bleomicina/efeitos adversos , Fibrose Pulmonar/induzido quimicamente , Neoplasias Abdominais/tratamento farmacológico , Bleomicina/uso terapêutico , Doxorrubicina/uso terapêutico , Feminino , Humanos , Metástase Linfática , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Pessoa de Meia-Idade , Prednisona/uso terapêutico , Fibrose Pulmonar/diagnóstico por imagem , Fibrose Pulmonar/tratamento farmacológico , Radiografia , Remissão Espontânea
13.
Am J Clin Pathol ; 63(4): 559-63, 1975 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-1119447

RESUMO

Spontaneous platelet aggregation in an asymptomatic individual is described. The platelet-poor plasma of the subject greatly enhanced the response of normal platelet-rich plasma to adenosine diphosphate. The spontaneous platelet aggregation was easily inhibited by aspirin.


Assuntos
Adesividade Plaquetária , Agregação Plaquetária , Difosfato de Adenosina/farmacologia , Aspirina/farmacologia , Depressão Química , Teste de Tolerância a Glucose , Humanos , Masculino , Pessoa de Meia-Idade , Agregação Plaquetária/efeitos dos fármacos
14.
J Neurosurg ; 82(3): 430-5, 1995 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-7861221

RESUMO

The goal of this study was to determine the antitumor activity and toxicity of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) plus recombinant interferon-alpha (IFN-alpha) in patients with recurrent glioma. As single agents, both BCNU and IFN-alpha can cause tumor regression in patients with recurrent glioma. In vitro studies suggest synergy between the two agents. Thirty-five patients in whom computerized tomography (CT) or magnetic resonance (MR) evidence was obtained of progressive astrocytoma, oligoastrocytoma, or oligodendroglioma received recombinant IFN-alpha 2a (12 x 10(6) U/m2 intramuscularly) on Days 1 through 3 and BCNU (150 mg/m2 intravenously) on Day 3 of each 6-week cycle. All patients had tumor progression despite radiation therapy and had received no prior chemotherapy. Response was assessed by CT or MR evidence and by neurological examination while the patients were on a regimen of stable or decreasing doses of corticosteroids. All patients could be evaluated for response and toxicity. Twenty-nine percent of the patients demonstrated objective tumor regression; 37% remained stable for more than 6 months and 25% were stable for less than 6 months. The median duration of response to IFN-alpha and BCNU was 9.9 months and the median survival for all patients was 13.3 months. Toxicity consisted primarily of moderate myelosuppression, venous irritation, vomiting, flulike symptoms, and transient reversible exacerbation of underlying neurological symptoms. The use of BCNU plus IFN-alpha is a safe, active regimen in the treatment of patients with recurrent glioma who have failed to respond to prior radiation therapy. The contribution of IFN to the antitumor activity observed in this study compared with that previously described with BCNU alone cannot be assessed from this trial.


Assuntos
Neoplasias Encefálicas/terapia , Carmustina/uso terapêutico , Glioma/terapia , Interferon-alfa/uso terapêutico , Recidiva Local de Neoplasia/terapia , Adulto , Idoso , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/mortalidade , Terapia Combinada , Feminino , Glioma/tratamento farmacológico , Glioma/mortalidade , Humanos , Interferon alfa-2 , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/mortalidade , Prognóstico , Proteínas Recombinantes , Análise de Regressão , Indução de Remissão , Taxa de Sobrevida , Estados Unidos
15.
Am J Clin Oncol ; 14(2): 152-5, 1991 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-2028922

RESUMO

Sixty-two patients with biopsy-proven, measurable disseminated malignant melanoma received either the combination IFN-alpha 2A with BCNU (30 patients) or the combination cimetidine with BCNU (32 patients) in parallel noncomparative Phase II trials. From patients receiving IFN-alpha 2A plus BCNU, we observed a 7% response rate: 1 complete response (CR) and 1 partial response (PR) (soft tissue disease with durations of 6.9 and 11.5+ months, respectively). Median time to progression (MTP) was 1.8 months and median survival time (MST) was 3.8 months. Myelosuppression and a flu-type illness were the most common toxicities. From patients receiving cimetidine plus BCNU, the response rate was 16%: 4 PRs (soft tissue disease, 3.8 months; visceral, 2.1, 4.0+, and 9.7 months) and 1 CR (soft tissue, 14.3+ months). MTP and MST were 1.9 and 5.5 months, respectively. Myelosuppression and nausea/vomiting were the most common side effects. Although each of these regimens had great conceptual allure, neither offered any durable impact on the natural history of disseminated malignant melanoma. Nevertheless, alternative combinations of biological response modifiers (BRMs) and BRMs with biochemical modulators or cytotoxic agents may provide some useful alternatives for further clinical investigations.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carmustina/uso terapêutico , Cimetidina/administração & dosagem , Interferon-alfa/uso terapêutico , Melanoma/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carmustina/administração & dosagem , Carmustina/efeitos adversos , Cimetidina/efeitos adversos , Avaliação de Medicamentos , Feminino , Humanos , Interferon alfa-2 , Interferon-alfa/efeitos adversos , Masculino , Melanoma/terapia , Pessoa de Meia-Idade , Proteínas Recombinantes , Indução de Remissão , Taxa de Sobrevida , Fatores de Tempo
16.
Am J Clin Oncol ; 20(5): 490-2, 1997 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-9345334

RESUMO

Adoptive immunotherapy (AI) with interleukin-2 (IL-2) and lymphokine-activated killer cells (LAK) is an antineoplastic modality in which immune-activated cells are administered to a host with advanced cancer in an attempt to mediate tumor regression. Levamisole (LEV), an immune stimulant, has been suggested to have therapeutic effectiveness in a variety of cancers. After a phase I trial of recombinant IL-2 plus LEV, a phase II trial of this combination was conducted in patients with advanced malignant melanoma. Nineteen patients were entered in the trial. They received IL-2 at 3 x 10(6) U/m2 subcutaneously daily x 5 plus LEV 50 mg/ m2 orally three times daily (p.o. t.i.d.) x 5. Patients were reevaluated at four-week intervals. None of the patients achieved a partial or complete regression (PR, CR). The median time to treatment failure (refusal, progression, or off study due to toxicity) was 56 days. Grade IV toxicities included vomiting (3 patients), lethargy (1 patient), and musculoskellar pain (1 patient). This regimen is not recommended for further testing in patients with advanced malignant melanoma.


Assuntos
Adjuvantes Imunológicos/uso terapêutico , Interleucina-2/uso terapêutico , Levamisol/uso terapêutico , Melanoma/terapia , Adjuvantes Imunológicos/administração & dosagem , Adjuvantes Imunológicos/efeitos adversos , Administração Oral , Adulto , Idoso , Intervalos de Confiança , Progressão da Doença , Feminino , Humanos , Imunoterapia Adotiva , Injeções Subcutâneas , Interleucina-2/administração & dosagem , Interleucina-2/efeitos adversos , Células Matadoras Ativadas por Linfocina/imunologia , Levamisol/administração & dosagem , Levamisol/efeitos adversos , Masculino , Pessoa de Meia-Idade , Dor/etiologia , Proteínas Recombinantes , Indução de Remissão , Fases do Sono/imunologia , Taxa de Sobrevida , Resultado do Tratamento , Recusa do Paciente ao Tratamento , Vômito/etiologia
17.
Postgrad Med ; 77(6): 165-74, 1985 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-3887344

RESUMO

Effective cancer chemotherapeutic agents were developed rapidly during the 1940s, 1950s, and 1960s. With recognition of the curability with chemotherapy of certain selected advanced cancers the emphasis of treatment has changed from a palliative to a curative mode. Several important biological advances, such as increased understanding of pharmacokinetics and the principles of combination chemotherapy, have strongly influenced the administration of chemotherapeutic agents. Other major conceptual changes, such as the recognition that regional lymph nodes are not effective barriers to tumor spread, have also had a major impact on the course of cancer treatment. The 1980s will be as productive as the preceding decades, but it is difficult at this time to determine if biologic response modifiers, monoclonal antibodies, differentiating agents, or some other as yet unrecognized therapy will be the major advance.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias/tratamento farmacológico , Alquilantes/história , Alquilantes/uso terapêutico , Antineoplásicos/história , História do Século XVI , História do Século XVII , História do Século XX , História Antiga , Humanos , Neoplasias/história
18.
J La State Med Soc ; 146(8): 359-61, 1994 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-7930868

RESUMO

Prospective randomized trial is the gold standard in clinical research. Randomized trials tend to reduce and even eliminate investigator and patient bias. A poorly-designed or improperly randomized study involving human subjects that will not or cannot answer a scientific question is by definition unethical. However, a well-designed clinical trial is not inherently ethical. Physicians involved in a randomized trial must make the intellectually honest admission that the best therapy for the individual's disease is not yet known. The ultimate protection for human subjects who volunteer to participate in clinical trials is the responsible investigator himself. In patients with advanced cancer there are three primary factors motivating participation: hope that the new treatment will offer a better chance for controlling disease; altruism that even if the treatment did not help them as an individual it might ultimately help others; and trust that the physician would not recommend that the patient enter investigational therapy unless he thought it might be helpful.


Assuntos
Ética Médica , Neoplasias/terapia , Ensaios Clínicos Controlados Aleatórios como Assunto/normas , Experimentação Humana Terapêutica , Humanos , Neoplasias/prevenção & controle , Seleção de Pacientes , Sujeitos da Pesquisa , Relações Pesquisador-Sujeito , Medição de Risco , Valores Sociais , Confiança , Incerteza
19.
J La State Med Soc ; 145(4): 175-7, 1993 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-8486991

RESUMO

Effective systemic cancer therapy has evolved during the past 50 years. Prior to that time a variety of treatments were attempted, many of which seemed to have had their origins in sorcery rather than science. The 1950s and 1960s produced an explosion of knowledge and many of the chemotherapeutic agents in use today were synthesized during that time frame. Currently we are exploring a variety of new therapeutic approaches to cancer, and the future promises to be increasingly productive.


Assuntos
Antineoplásicos/história , Neoplasias/história , História do Século XVII , História do Século XX , Humanos
20.
J La State Med Soc ; 147(4): 147-8, 1995 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-7775840

RESUMO

Current epidemiologic and carcinogenesis data are lending credence to the hypothesis that individual cancers have specific causes. Because of this, most cancers are at least potentially preventable. Primary prevention, with removal of specific etiological agents, is the best means of prevention, such as elimination of tobacco smoke. Short of knowing the specific etiology, new chemo-prevention techniques are now being studied evaluating hormonal agents, anti-inflammatory drugs, and the structural analogs of vitamin A.


Assuntos
Neoplasias/prevenção & controle , Aspirina/administração & dosagem , Aspirina/efeitos adversos , Exposição Ambiental/efeitos adversos , Feminino , Finasterida/administração & dosagem , Finasterida/efeitos adversos , Humanos , Isotretinoína/administração & dosagem , Isotretinoína/efeitos adversos , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Neoplasias/etiologia , Fatores de Risco , Tamoxifeno/administração & dosagem , Tamoxifeno/efeitos adversos
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