RESUMO
Patients with stage IIIB breast carcinoma represent only a small proportion of women with breast cancer in western countries but may constitute up to 50% of cases in underdeveloped countries. The prognosis remains poor despite aggressive treatment. Nineteen patients (11 with inflammatory breast carcinoma) received at least three courses of neoadjuvant chemotherapy of methotrexate, vinblastine, adriamycin, cisplatin, and folinic acid (MVAC/FA) followed by mastectomy. Six months of cyclophosphamide, methotrexate, and 5-fluorouracil were given after surgery. Radiation therapy followed chemotherapy. Seventy percent of patients achieved complete and 14% partial response after MVAC/FA chemotherapy alone. Eleven patients (58%) survived 5 years, and 30% survived at least 8 years. The addition of cisplatin in combination chemotherapy used as first-line treatment for stage IIIB breast carcinoma was well tolerated, resulted in higher response rates, and appeared to have an effect on overall survival.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/mortalidade , Cisplatino/administração & dosagem , Doxorrubicina/administração & dosagem , Esquema de Medicação , Feminino , Fluoruracila/administração & dosagem , Humanos , Leucovorina/administração & dosagem , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estadiamento de Neoplasias , Prognóstico , Análise de Sobrevida , Vimblastina/administração & dosagemRESUMO
Alpha 2-macroglobulin, a major glycoprotein component of plasma, is unique in its capacity to bind and inhibit the proteolytic activities of all classes of proteinases. Since proteinases implicated in cancer dissemination (type-IV collagenase, plasminogen activator, cathepsins B) are normal constitutents of blood, we have explored the hypothesis that elevated tissue levels of activated proteinases bound to alpha 2M might be detected in plasma of patients with cancer. To test this premise, blood was collected from 149 subjects (33 healthy controls, 31 patients with infections and non-malignant diseases, 16 with myeloproliferative disease, 10 with gastrointestinal cancer, 7 with genito-urinary cancer, 16 with lung cancer, 14 with lymphoma, 11 with miscellaneous cancers and 11 with chronic lymphocytic leukemia and myeloma). Plasma was assayed for alpha 2M-proteinase complexes using a sandwich ELISA which employs a mouse monoclonal antibody (MAb) that binds to a neo-antigenic determinant on complexed alpha 2M and a rabbit polyclonal anti-native human alpha 2M antibody. The concentration of complexed alpha 2M in healthy controls was 14.2 +/- 9.8 micrograms/ml (mean +/- standard deviation). No significant differences in complexed alpha 2M were noted between normal and cancer groups (range 7.4-14.6 micrograms/ml). On the basis of these data, we propose that, in patients with cancer, activated proteinases are bound locally to inhibitors in the tissues and are not available to form complexes with plasma alpha 2M. An alternative explanation is that proteinases are not secreted in excess by cancer cells in vivo.
Assuntos
Endopeptidases/sangue , Neoplasias/sangue , alfa-Macroglobulinas/análise , Adulto , Idoso , Análise de Variância , Biomarcadores Tumorais/sangue , Ensaio de Imunoadsorção Enzimática , Feminino , Doenças Hematológicas/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Valores de ReferênciaAssuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/toxicidade , Cisplatino/administração & dosagem , Ensaios Clínicos como Assunto , Neoplasias Colorretais/patologia , Avaliação de Medicamentos , Feminino , Fluoruracila/administração & dosagem , Humanos , Leucovorina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Metástase NeoplásicaAssuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Doxorrubicina/análogos & derivados , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Ósseas/secundário , Carcinoma Pulmonar de Células não Pequenas/patologia , Doxorrubicina/efeitos adversos , Doxorrubicina/uso terapêutico , Avaliação de Medicamentos , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de NeoplasiasRESUMO
Mucositis is one of the major problems encountered after the administration of systemic chemotherapy. Leucovorin, routinely used as a rescue agent for methotrexate may reduce toxicity, but may also reduce the effectiveness of the chemotherapeutic agent. If leucovorin is administered as a mouth wash, local toxicity may be reduced without loss of methotrexate efficacy. In order to study this, 15 normal human volunteers were given leucovorin mouth wash and then had plasma determinations of 5-methyl-tetrahydrofolate and citrovorum factor. Small but statistically significant increases in plasma levels of 5-methyl-tetrahydrofolate were observed with no increase in levels of plasma citrovorum factor. It is concluded therefore that a small amount of leucovorin is absorbed systemically when administered as a mouth wash, but such an amount would most likely not be significant enough to reduce the effect of methotrexate therapy, but may reduce mucositis.
Assuntos
Leucovorina/metabolismo , Antissépticos Bucais/metabolismo , Absorção , Administração Oral , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doenças da Boca/prevenção & controleRESUMO
To determine the frequency and prognostic importance of pretreatment clinical characteristics in patients currently undergoing treatment for stage III non-small-cell lung cancer (NSCLC), data were collected on 378 patients receiving high-dose (120 mg/m2) cisplatin plus vinca alkaloid combination chemotherapy regimens since 1978. Variables analyzed included age, sex, weight loss, performance status, histologic subtype, presence of extrathoracic metastases, number of metastatic organ sites, presence of liver, bone, or brain involvement, prior radiation or surgery, and serum lactate dehydrogenase (LDH). The effect of a major response to chemotherapy on survival was also investigated. Using multivariable analyses, the following were found to be associated with outcome: initial performance status, with patients having a performance status of 80% to 100% having an increased major objective response rate and survival; bone metastases, which were adversely predictive of response rate and survival; elevated serum LDH and male sex, both of which were associated with shortened survival and remission duration; and the presence of two or more extrathoracic metastatic organ sites, which was associated with shorter survival. When major objective response with chemotherapy was included in a conditional multivariable analysis, it was strongly associated with longer median survival. Information from this analysis may be useful when comparing the response data of completed studies in similar patients, in designing future trials, and in the selection of cisplatin plus vinca alkaloid therapy for individual patients with advanced NSCLC.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Coleta de Dados , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Prognóstico , Estatística como AssuntoRESUMO
In prior trials, mitomycin, vindesine, and cisplatin have each been shown to have reproducible antitumor activity as single agents when used in the treatment of patients with non-small cell lung cancer. The two-drug combinations of vindesine plus high-dose cisplatin or mitomycin have shown an improved major response rate and manageable toxicity in prior trials. In this report, 90 patients with stage III non-small cell lung cancer were treated with the three-drug combination of mitomycin (8 mg/m2), vindesine (3 mg/m2), and high-dose cisplatin (120 mg/m2). Eighty-seven patients (97%) were adequate for both response and toxicity. Major objective responses occurred in 60% of the patients. The toxicity of this regimen was predictable and manageable when established supportive care measures were employed. Based on the response rate observed, the combination of these three agents merits further study in randomized trials against other chemotherapeutic regimens and consideration of its use in adjuvant and preoperative settings.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/toxicidade , Carcinoma/patologia , Cisplatino/administração & dosagem , Ensaios Clínicos como Assunto , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Mitomicina , Mitomicinas/administração & dosagem , Metástase Neoplásica , Vindesina/administração & dosagemRESUMO
Four consecutive trials were undertaken to study lorazepam at each of three dosage levels and diphenhydramine when used in combination with iv metoclopramide and dexamethasone in patients receiving cisplatin at 120 mg/m2. The combination containing diphenhydramine had been the most effective treatment identified in prior trials. Earlier studies have found lorazepam to be a useful adjunct to other antiemetic agents. Sixty-five patients who had never received chemotherapy or antiemetics were directly observed in the hospital for 24 hours following cisplatin. Overall, 56% of the patients experienced no emesis and 78.5% of the patients had two or fewer vomiting episodes during the study period. No significant differences were noted in the number of patients who experienced no emesis or two or fewer episodes among the four trials. More sedation was seen with the lorazepam-containing regimens; other side effects were similar in type and severity. The trial using the highest dose of lorazepam (1.5 mg/m2) demonstrated significantly greater patient satisfaction (P = 0.039) and less anxiety during therapy (P = 0.02) when compared with the diphenhydramine combination. We conclude that combinations of iv metoclopramide plus dexamethasone with either diphenhydramine or lorazepam are well tolerated and effective in controlling cisplatin-induced emesis. The regimens containing lorazepam produced better subjective evaluations, and the combination using the highest lorazepam dose tested showed superior patient satisfaction and less anxiety during therapy.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Dexametasona/uso terapêutico , Difenidramina/uso terapêutico , Lorazepam/uso terapêutico , Metoclopramida/uso terapêutico , Adulto , Idoso , Ansiedade , Cisplatino/efeitos adversos , Cisplatino/uso terapêutico , Ensaios Clínicos como Assunto , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Náusea/prevenção & controle , Cooperação do Paciente , Inquéritos e Questionários , Vômito/induzido quimicamente , Vômito/prevenção & controleRESUMO
4-Demethoxydaunorubicin (4-DMDR) is an orally active analog of daunorubicin that in preclinical testing has demonstrated greater antitumor activity and less cardiotoxicity than its parent compound. Thirty-two patients with metastatic non-small cell lung cancer received 4-DMDR at a dose of 40-50 mg/m2 orally every 21 days. Thirteen patients had received no prior chemotherapy. Among the 30 adequately treated patients, one major response lasting 5.2 months was observed. Leukopenia 10-14 days after treatment was the most commonly observed toxicity. With an overall observed major response rate of 3.3% in 30 patients, the predicted true response rate is less than or equal to 16% (p = 0.05). At the dose and schedule studied in this group of patients with non-small cell lung cancer, 4-DMDR had only marginal activity.
Assuntos
Antineoplásicos/uso terapêutico , Daunorrubicina/análogos & derivados , Neoplasias Pulmonares/tratamento farmacológico , Adulto , Idoso , Daunorrubicina/uso terapêutico , Daunorrubicina/toxicidade , Avaliação de Medicamentos , Feminino , Humanos , Idarubicina , Leucopenia/induzido quimicamente , Masculino , Pessoa de Meia-IdadeRESUMO
Adenocarcinoma of unknown primary origin (ACUP) is a common oncologic problem for which there is no standard therapy. Forty-two patients with metastatic tumor were identified as having ACUP after extensive evaluation failed to reveal a primary site of disease. They were treated with an investigational chemotherapy regimen consisting of vindesine and doxorubicin. Of the 38 evaluable patients, six (16%) had major responses to chemotherapy. The median duration of response was 4 months. The median survival of the responding patients has not been reached, but is greater than 8 months. The median survival of the nonresponding patients was 6 months. Vindesine and doxorubicin were well tolerated. The major toxicity was leukopenia, with a median wbc count nadir of 2600/mm. We conclude that the combination of vindesine and doxorubicin has some activity in ACUP, but does not improve the response rate seen with other regimens.
Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Adenocarcinoma/secundário , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Doxorrubicina/administração & dosagem , Feminino , Humanos , Leucopenia/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Vimblastina/administração & dosagem , Vimblastina/análogos & derivados , VindesinaRESUMO
Ninety patients with stage-3 non-small cell lung cancer were given vindesine (3 mg/sq m) plus mitomycin (10 mg/sq m). Data on response are available for 84 adequately treated individuals (93 percent). For patients who had received no prior chemotherapy, the rate of major objective response was 36 percent (20/55). For previously treated patients the rate of major response was 17 percent (5/29). The drugs were routinely administered in the outpatient department without difficulty. Moderate or severe myelosuppression, neurotoxic, nephrotoxic, or pulmonary toxic effects, nausea, and vomiting occurred in less than 15 percent of all studied patients. Three-drug extravasation ulcerations occurred in 1,129 administrations of chemotherapy (0.3 percent). There were two treatment-related deaths, one from sepsis and one from the combination of mitomycin-induced pulmonary and renal toxic effects. The combination of vindesine plus mitomycin is an active, well-tolerated outpatient regimen for patients with non-small cell lung cancer who have not previously received chemotherapy. Further trials are warranted to compare this regimen to other active combinations and to use it as a component of a program of treatment using alternating regimens of chemotherapy.