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2.
Ann Oncol ; 21(3): 493-497, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19625343

RESUMO

BACKGROUND: Because of the single-agent activity of irinotecan hydrochloride, combination of irinotecan and docetaxel treatment against metastatic breast cancer (MBC) should be evaluated. PATIENTS AND METHODS: Single-stage phase 2 study of irinotecan and docetaxel to evaluate tumor response, toxicity, time to progression, and overall survival was carried out. Regimen of docetaxel (25 mg/m(2)) and irinotecan (70 mg/m(2)) was administered on days 1 and 8 of each 3-week cycle. Patients had histologically confirmed breast adenocarcinoma and metastatic cancer measurable with RECIST. RESULTS: Of 70 patients enrolled, 64 were assessable. Prior treatment with an anthracycline and a taxane was required. Eighteen (28%) patients [95% confidence interval (CI) 15% to 31%] had tumor response, plus four patients had stable disease (less than 30% decrease in sum of longest diameter and less than 20% increase) for >6 months. The clinical benefit rate was 34% overall. Median duration of tumor response was 6.7 months (95% CI 4.2-37.7 months); median follow-up was 18.6 months (range 8.5-37.7 months). The most common severe adverse events included fatigue [n = 16 (25%)] and neutropenia [n = 13 (20%)]. CONCLUSIONS: Weekly dosing of combination of irinotecan and docetaxel is active against MBC. However, the response rate to our regimen was not significantly better than single-agent docetaxel. Other schedules of irinotecan plus docetaxel should be considered for future studies.


Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos , Recidiva Local de Neoplasia/tratamento farmacológico , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/patologia , Camptotecina/administração & dosagem , Camptotecina/análogos & derivados , Docetaxel , Feminino , Seguimentos , Humanos , Irinotecano , Pessoa de Meia-Idade , Metástase Neoplásica , Recidiva Local de Neoplasia/patologia , Terapia de Salvação , Taxa de Sobrevida , Taxoides/administração & dosagem , Resultado do Tratamento
3.
J Clin Oncol ; 16(7): 2528-33, 1998 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-9667274

RESUMO

PURPOSE: Extrahepatic metastasis represents a frequent pattern of disease progression when fluorodeoxyuridine (FUDR) is given by the intraarterial route for the treatment of unresectable colorectal liver metastases. Systemic fluorouracil (5-FU) plus leucovorin was added to intrahepatic FUDR to prolong the duration of disease control. METHODS: Only patients with colorectal cancer who had evidence of unresectable metastases confined to the liver were eligible. Laparotomy was performed to establish arterial perfusion of the liver. Cycles of intrahepatic FUDR followed by a 1-week rest period then intravenous chemotherapy with 5-FU plus leucovorin were administered until maximal regression of hepatic metastases. Maintenance chemotherapy with 5-FU plus leucovorin was then given until disease progression. RESULTS: Fifty-seven patients entered this trial; four patients (7%) were ineligible and 13 (23%) did not receive any chemotherapy on study because of findings at laparotomy. The 40 eligible patients who began chemotherapy are included in the statistical analyses. Twenty-five patients (62% of those who received chemotherapy) experienced regression of liver metastases. The median time to tumor progression was 9 months, but only 3% remained progression-free at 24 months. The median survival duration was 18 months. Toxicity was tolerable with no cases of biliary sclerosis. One treatment-related fatality due to sepsis was observed. CONCLUSION: Although short-term treatment results appear to be somewhat better than we have previously observed with intrahepatic FUDR alone, the sequential regimen did not have an impact on long-term, progression-free survival in patients with unresectable liver metastases. We are now investigating this regimen as surgical adjuvant therapy in selected patients following hepatic metastasectomy where this aggressive approach might have a greater therapeutic effect in the minimal residual disease setting.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/patologia , Neoplasias Hepáticas/tratamento farmacológico , Adulto , Idoso , Neoplasias Colorretais/cirurgia , Intervalo Livre de Doença , Esquema de Medicação , Feminino , Floxuridina/administração & dosagem , Fluoruracila/administração & dosagem , Artéria Hepática , Humanos , Infusões Intra-Arteriais , Infusões Intravenosas , Leucovorina/administração & dosagem , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
4.
Chest ; 74(5): 531-6, 1978 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-216531

RESUMO

Serial fiberoptic bronchoscopic examinations were performed during intensive chemotherapy with a combination of drugs in 77 previously untreated patients with small cell carcinoma of the lung. Before treatment, bronchoscopic examination revealed evidence of cancer in 93 percent (70) of the 75 patients studied at that time, including 8 percent (six) in whom the tumor was not evaluable on the chest x-ray film. After therapy was initiated, 36 percent (29) of the 81 procedures performed in patients with a complete response radiographically and 62 percent (33) of the 53 bronchoscopic procedures in those with a partial response or no response showed evidence of tumor. In both of these groups, patients with abnormal findings on endoscopic examination had a much higher rate of relapsing tumor of the chest within a 12-week period. Progression of intrathoracic tumor was first detected solely by bronchoscopic examination in 22 percent (seven) of the 32 episodes of progression. In our hands, repeated fiberoptic bronchoscopic procedures during chemotherapy for small cell carcinoma have yielded information not apparent from the chest x-ray film in a significant number of patients.


Assuntos
Broncoscopia , Carcinoma de Células Pequenas/diagnóstico , Neoplasias Pulmonares/diagnóstico , Carcinoma de Células Pequenas/tratamento farmacológico , Quimioterapia Combinada , Tecnologia de Fibra Óptica , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Recidiva , Risco
5.
Am J Clin Oncol ; 23(5): 534-7, 2000 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11039519

RESUMO

At present there remains a need for more effective systemic therapy in advanced pancreatic cancer. Some studies have suggested that infusional chemotherapy schedules and biomodulation of 5-fluorouracil (5-FU) may improve the therapeutic outcome in advanced colon cancer. One such regimen that uses continuous infusion 5-FU, weekly leucovorin, daily dipyridamole, and intermittent mitomycin-C has activity in both colon and unresectable pancreatic carcinoma. The intent of this trial was to test the effectiveness of this four-drug regimen in advanced pancreatic cancer. Patients received 5-FU 200 mg/m2 daily by continuous infusion, leucovorin 30 mg/m2 IV weekly, mitomycin-C 10 mg/m2 day 1, and dipyridamole 75 mg orally four times daily for 5 weeks. After a 1-week break, treatment cycles were repeated every 6 weeks. Eligibility included biopsy-proven advanced measurable pancreatic cancer, Eastern Cooperative Oncology Group performance status 0 and 2, and no prior systemic chemotherapy. Of 46 evaluable patients, 9 partial responses and 1 complete tumor response were seen, for an overall response rate of 22% (95% confidence interval 11-36%). The median survival in the group of 50 patients registered to this trial was 4.6 months, with a range of 0.33 to 40.2 months. Toxicity was manageable, with the most common toxicities (> or =grade III National Cancer Institute Common Toxicity Criteria) being anorexia (13%), stomatitis (17%), and hand-foot syndrome (13%). Of note, little severe hematologic toxicity and no significant headaches were reported. Although some patients did respond, the therapeutic results are not encouraging enough to take this regimen to phase III testing.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Dipiridamol/administração & dosagem , Feminino , Fluoruracila/administração & dosagem , Humanos , Leucovorina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Mitomicina/administração & dosagem , Análise de Sobrevida , Falha de Tratamento
6.
Ann Clin Lab Sci ; 30(3): 249-58, 2000 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-10945564

RESUMO

Immunotherapy using a monoclonal antibody against the human epidermal growth factor receptor 2 protein, HER-2/neu, has proven to be clinically efficacious in about one-half of breast cancer patients who exhibit strong (3+) plasmalemmal immunoreactivity for this protein. The tumoricidal effect of this antibody relies in part upon antibody-dependent cell-mediated cytotoxicity. This report provides observations on certain factors or circumstances which could have an impact on this aspect of the therapeutic approach. These include: (1) concurrent medications; (2) the composition (immunophenotype) of peritumoral lymphocytes and the generally limited numbers of intratumoral T-lymphocytes/natural killer (NK) cells, monocytes, and neutrophilic granulocytes; (3) the presence of circulating HER-2/neu antigens which might bind the exogenous antibody and lead to immune complex formation; (4) the variable co-expression in the tumor of cytokines known to downregulate NK cell function (ie, transforming growth factor-beta1 [TGF-beta1] and platelet-derived growth factor [PDGF]-AB); and (5) the tumoral and/or stromal immunoreactivity for angiotensin-converting enzyme, which forms a part of one of the pathways for the activation of latent TGF-beta1 and for the biosynthesis of PDGF-AB. These observations provide an immunologic perspective for the use of monoclonal antibody therapy in HER-2/neu protein-receptor-positive breast carcinoma and suggest a role for the clinical laboratory in identifying potential avenues for additional manipulations of the immune system in individual cases in order to enhance the therapeutic response.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Imuno-Histoquímica/métodos , Receptor ErbB-2/análise , Idoso , Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/imunologia , Feminino , Humanos , Linfócitos/imunologia , Linfócitos do Interstício Tumoral/classificação , Linfócitos do Interstício Tumoral/imunologia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Trastuzumab
8.
Cancer Treat Rep ; 62(10): 1521-5, 1978 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-709554

RESUMO

Thirty-six patients with advanced colorectal carcinoma who had not received prior chemotherapy and had tumor sites measurable or evaluable for response received methyl-CCNU at a dose of 175 mg/m2 orally on Day 1 plus 5-fluorouracil at a dose of 30 mg/kg/24 hours by continuous iv infusion for 120 hours (Days 1-5). Doses were chosen to approach the maximum which could be administered in combination. The cycle was repeated 6 weeks later. Objective partial responses occurred in six patients (17%), with five responses apparent after the first cycle and one additional response after the second cycle. The response duration ranged from 1.5 to 18+ months (median, 5 months). Dose-limiting toxic effects included mucositis in 18 patients (50%) and dermatitis in nine patients (25%), while leukopenia (less than 4000 cells/mm3) and thrombocytopenia (less than 100,000 platelets/mm3) were observed on at least one occasion during therapy in 52% and 46% of patients, respectively. 5-Fluorouracil administration by infusion avoided overlapping myelosuppression and allowed a higher total dose to be given with methyl-CCNU. However, the response to the combination did not exceed the results anticipated for the use of either drug alone.


Assuntos
Neoplasias do Colo/tratamento farmacológico , Fluoruracila/administração & dosagem , Compostos de Nitrosoureia/administração & dosagem , Neoplasias Retais/tratamento farmacológico , Semustina/administração & dosagem , Adulto , Idoso , Doenças da Medula Óssea/induzido quimicamente , Antígeno Carcinoembrionário/análise , Quimioterapia Combinada , Feminino , Fluoruracila/efeitos adversos , Fluoruracila/uso terapêutico , Humanos , Infusões Parenterais , Masculino , Pessoa de Meia-Idade , Semustina/efeitos adversos , Semustina/uso terapêutico
9.
Cancer ; 43(4): 1568-71, 1979 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-87252

RESUMO

Two patients with myelofibrosis developed fever, leg pain and periostitis. The first patient had myelofibrosis with myeloid metaplasia and was symptomatic for months before x-rays showed periosteal new bone formation in the lower extremities. He subsequently developed periostitis of both upper extremities. Radiation of the lower extremities resulted in significant pain relief. The second patient had a past history of polycythemia vera and experienced painful periostitis of the tibiae and fibulae. 99mTechnetium pyrophosphate bone scans showed increased uptake in the involved bones in both patients. Asymptomatic or painful periostitis may be related to the increased bone blood flow associated with myelofibrosis. Radiation can afford successful palliation in the severely symptomatic patient.


Assuntos
Periostite/complicações , Mielofibrose Primária/complicações , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartropatia Hipertrófica Secundária/diagnóstico , Osteogênese , Cuidados Paliativos , Periostite/diagnóstico por imagem , Periostite/patologia , Periostite/fisiopatologia , Periostite/terapia , Policitemia Vera/complicações , Mielofibrose Primária/diagnóstico por imagem , Mielofibrose Primária/patologia , Mielofibrose Primária/terapia , Radiografia
10.
Clin Pharm ; 3(6): 618-21, 1984.
Artigo em Inglês | MEDLINE | ID: mdl-6391784

RESUMO

Droperidol, metoclopramide, and prochlorperazine were compared in a double-blind crossover trial to determine their relative effectiveness in preventing and controlling the nausea and vomiting caused by cisplatin-containing chemotherapy. Twenty-five patients receiving cisplatin-containing chemotherapy for various malignancies were entered into this trial with 14 patients completing the three-drug randomization sequence. This was the patient's first exposure to cisplatin. Each antiemetic was administered in a diluted 50 ml i.v. injection over 15 minutes beginning 0.5 hour before cisplatin and 1.5, 3.5, 5.5, and 8.5 hours after cisplatin. Dosages of antiemetics for doses of cisplatin greater than or equal to 100 mg/sq m were droperidol 2.5 mg, metoclopramide 2 mg/kg, or prochlorperazine 5 mg in each infusion. For doses of cisplatin less than 100 mg/sq m, the dosages were droperidol 2.5 mg for the first two doses and 1.25 mg for subsequent doses, metoclopramide 1 mg/kg, or prochlorperazine 5 mg for each dose. The median number of emetic episodes for the first 24 hours were as follows: droperidol 3.2; metoclopramide 1.8; prochlorperazine 3.7. There was a significant difference in number of emetic episodes demonstrating antiemetic superiority of metoclopramide over both droperidol and prochlorperazine. For these 14 patients completing the trial, eight preferred metoclopramide, two preferred prochlorperazine, one preferred droperidol, and three had no preference. At the doses used in this study, the antiemetic efficacy of metoclopramide was superior to either droperidol or prochlorperazine.


Assuntos
Antieméticos/uso terapêutico , Cisplatino/efeitos adversos , Adulto , Idoso , Cisplatino/uso terapêutico , Ensaios Clínicos como Assunto , Método Duplo-Cego , Droperidol/uso terapêutico , Feminino , Humanos , Masculino , Metoclopramida/uso terapêutico , Pessoa de Meia-Idade , Neoplasias/tratamento farmacológico , Proclorperazina/uso terapêutico , Distribuição Aleatória
11.
Oncology ; 51 Suppl 1: 2-7, 1994 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-7970505

RESUMO

Several randomized, placebo-controlled clinical trials have demonstrated that megestrol acetate therapy can result in appetite stimulation and nonfluid weight gain in patients with cancer anorexia/cachexia. The present trial was designed to compare megestrol acetate doses ranging from 160 to 1,280 mg/day. day. This trial randomly assigned 342 evaluable patients with cancer anorexia/cachexia to receive oral megestrol acetate at doses of 160, 480, 800 and 1,280 mg/day. Patients were evaluated monthly by history, examination and patient-completed questionnaires, as well as by serum albumin levels. The data demonstrate a positive dose-response effect for megestrol acetate on appetite stimulation (p = 0.02). there was a trend for more nonfluid weight gain with higher drug doses. Megestrol acetate was well tolerated in this group of patients with advanced malignant disease. The positive dose-response effect observed for megestrol acetate on appetite stimulation supports both the prestudy hypothesis and findings in the literature. The optimal dose in this study seemed to be 800 mg/day; no further benefit was derived from using the higher dose. Nonetheless, it may be reasonable to start with lower initial doses in routine clinical practice, taking into account dosage form, availability and cost of therapy.


Assuntos
Anorexia/tratamento farmacológico , Caquexia/tratamento farmacológico , Megestrol/análogos & derivados , Síndromes Paraneoplásicas/tratamento farmacológico , Administração Oral , Adulto , Idoso , Idoso de 80 Anos ou mais , Apetite/efeitos dos fármacos , Feminino , Seguimentos , Humanos , Masculino , Megestrol/administração & dosagem , Megestrol/efeitos adversos , Acetato de Megestrol , Pessoa de Meia-Idade , Estudos Prospectivos , Inquéritos e Questionários , Taxa de Sobrevida , Fatores de Tempo , Aumento de Peso
12.
Invest New Drugs ; 18(3): 275-80, 2000 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-10958598

RESUMO

Current systemic treatment options for patients with relapsed gliomas are limited. The topoisomerase I inhibitor topotecan has demonstrated broad antitumor activity in both preclinical studies as well as a number of phase I and II trials in humans. Studies in primates have shown good cerebrospinal fluid levels of topotecan following systemic administration. We therefore performed this phase II trial in patients who developed evidence of progressive glioma after definitive radiation therapy. Patients were treated with 1.5 mg/m2 intravenously daily for 5 consecutive days repeated every three weeks. For patients who had received prior nitrosourea-containing chemotherapy, the starting dose was 1.25 mg/m2. Thirty-three patients were entered on this study. All patients were eligible and evaluable for both response and toxicity. Seven patients experienced grade 4 leukopenia with 2 of these patients dying of infection-related complications. Six of these seven patients were not taking anticonvulsants during treatment. Nine patients developed grade 3-4 thrombocytopenia, seven of whom were not taking anticonvulsants. Nonhematologic side effects were infrequent and manageable. One patient experienced a partial response to this treatment for an overall response rate of 3% (95% binomial confidence interval 0.3%-20.4%). The median time to progression was 14.9 weeks and median survival 19.9 weeks. Topotecan at this dose and schedule showed no substantial activity in relapsed gliomas.


Assuntos
Antineoplásicos/uso terapêutico , Glioma/tratamento farmacológico , Topotecan/uso terapêutico , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Topotecan/efeitos adversos
13.
Cancer ; 92(2): 420-33, 2001 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-11466698

RESUMO

BACKGROUND: The current study was conducted to determine whether the addition of interferon-alpha (IFN-alpha) to treatment with radiation therapy and carmustine (BCNU) improves time to disease progression or overall survival in patients with high-grade glioma. METHODS: Patients with anaplastic astrocytoma, anaplastic oligoastrocytoma, glioblastoma multiforme, or gliosarcoma received radiation therapy plus BCNU as initial therapy. Subsequently, patients without tumor progression at the completion of radiation therapy were stratified by age, extent of surgery, tumor grade and histology, Eastern Cooperative Oncology Group performance status, and treating institution, and then were randomly assigned to receive either BCNU alone (200 mg/m(2) on Day 1) or BCNU (150 mg/m(2) on Day 3) plus IFN--alpha (12 million U/m(2) on Days 1-3, Weeks 1, 3, and 5) every 7 weeks for a maximum of 6 cycles. RESULTS: Of the 383 patients enrolled in the study, 275 eligible patients were randomized. There was no significant difference with regard to time to disease progression or overall survival between the two groups. Patients receiving IFN-alpha experienced more fever, chills, myalgias, and neurocortical symptoms including somnolence, confusion, and exacerbation of neurologic deficits. Cox multivariate regression models confirmed known favorable prognostic variables including younger age, Grade 3 tumor (according to World Health Organization criteria), and greater extent of surgery. Cox and classification and regression tree analysis models also demonstrated that a normal baseline Folstein mini-mental status examination (MMSE) score was associated with better prognosis. CONCLUSIONS: IFN-alpha does not appear to improve time to disease progression or overall survival in patients with high-grade glioma and appears to add significantly to toxicity. The baseline MMSE score may serve as an independent prognostic factor and warrants further investigation.


Assuntos
Antineoplásicos Alquilantes/farmacologia , Antineoplásicos/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/radioterapia , Carmustina/farmacologia , Glioma/tratamento farmacológico , Glioma/radioterapia , Interferon-alfa/farmacologia , Adulto , Idoso , Antineoplásicos/administração & dosagem , Antineoplásicos Alquilantes/administração & dosagem , Neoplasias Encefálicas/patologia , Carmustina/administração & dosagem , Terapia Combinada , Progressão da Doença , Feminino , Glioma/patologia , Humanos , Interferon-alfa/administração & dosagem , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Análise de Sobrevida , Resultado do Tratamento
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