RESUMO
L1210 murine leukemia and CEM human lymphoblastoid leukemia cells were exposed to vincristine sulfate in vitro. The response of these cell lines to this agent was measured by the colony-forming ability of L1210 cells in soft agar and inhibition of growth of CEM in suspension culture. Incremental increases of vincristine concentrations in excess of 2 x 10(-9) M produced a progressive reduction of survival of L1210 cells and suppression of CEM growth under the condition of constant drug exposure. A maximum cytotoxic effect was reached with drug concentrations between 10(-8) and 10(-7) M. When L1210 cells were exposed to vincristine for a variable length of time ranging from 0.5 to 24 hr, 10(-7) M produced a noticeable cytotoxic effect following an incubation of only 30 min. A 50% cell kill of L1210 cells and a 50% reduction of CEM cell growth were produced by 10(-7) M following a 1- to 3-hr period of exposure; 6 to 12 hr were required to produce a similar effect at a vincristine concentration of 10(-8) M. Therefore, the antitumor effect of vincristine is critically dependent on both concentration and duration of exposure. These data suggest the possibility that the effectiveness of vincristine as an antitumor agent could be enhanced if methods are developed to prolong exposure of neoplastic tissues for longer periods of time than currently produced by conventional methods of administration.
Assuntos
Leucemia L1210/tratamento farmacológico , Leucemia Linfoide/tratamento farmacológico , Vincristina/administração & dosagem , Animais , Divisão Celular/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Células Clonais/efeitos dos fármacos , Relação Dose-Resposta a Droga , Humanos , Camundongos , Fatores de TempoRESUMO
Using a sensitive radioimmunoassay, concentrations of vincristine and its products were determined in cerebrospinal fluid (CSF) and corresponding blood samples from four patients with lymphoma and two patients with leukemia who had received i.v. bolus injection of 2 mg vincristine. Serial samples of CSF were withdrawn from a CSF reservoir in two patients during a 24-hr period following injection. The first time point after injection at which measurable levels of vincristine were detected in the CSF was 30 min; the concentrations were within the lower range of sensitivity of the assay and were 20- to 30-fold lower than were corresponding serum samples. Despite a prolonged terminal half-life of vincristine in the serum (14.4 to 37.5 hr) following i.v. bolus injection, concentrations of vincristine in the CSF ranged between undetectable within the limits of the assay and 1.1 X 10(-9) M during the 24-hr period of observation. The highest CSF concentration of vincristine (2.6 X 10(-9) M) has been observed in a patient receiving cranial irradiation for active meningeal lymphoma. No measurable levels of vincristine or its products were detected in spot samples of CSF from three patients. Penetration of vincristine and its products into the CSF of humans after i.v. bolus injection appears to be very poor and may account for the uncommon occurrence of central neurotoxicity following its clinical use.
Assuntos
Vincristina/líquido cefalorraquidiano , Adolescente , Feminino , Meia-Vida , Humanos , Injeções Intravenosas , Cinética , Leucemia Linfoide/sangue , Leucemia Linfoide/líquido cefalorraquidiano , Leucemia Linfoide/tratamento farmacológico , Linfoma/sangue , Linfoma/líquido cefalorraquidiano , Linfoma/tratamento farmacológico , Masculino , Neoplasias Meníngeas/tratamento farmacológico , Neoplasias Meníngeas/metabolismo , Neoplasias Meníngeas/radioterapia , Pessoa de Meia-Idade , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/metabolismo , Fatores de Tempo , Vincristina/sangue , Vincristina/metabolismoRESUMO
Adult rhesus monkeys were given 2-mg/sq m i.v. bolus injections of radiochemically pure tritiated vincristine (VCR). Simultaneous specimens of blood and cerebrospinal fluid (CSF) were sampled from 5 min to 72 hr following injection. CSF was obtained from Ommaya reservoirs which had been implanted s.c. in each monkey. VCR and its metabolic and/or decomposition products rapidly entered the CSF producing low concentrations in this fluid; 5 min following injection, the concentration of VCR was 2.3 nM, whereas approximately a 100-fold greater concentration (203.8 nM) was attained in the plasma. Throughout a 3-day period of observation, constant, low levels of VCR and its metabolic and/or decomposition products (2.3 to 5.7 nM) were maintained in the CSF. The principal form of VCR present in the CSF 1 hr or more after i.v. injection was a water-soluble metabolite and/or decomposition product(s). Although the levels achieved in the CSF are unlikely to be lethal to tumor cells, the finding of persistent low concentrations of VCR and its metabolic and/or decomposition products in the CSF indicates prolonged exposure of neural tissue which might result in neurotoxicity, particularly cumulative neurotoxicity following multiple doses of VCR.
Assuntos
Vincristina/líquido cefalorraquidiano , Animais , Modelos Animais de Doenças , Cinética , Macaca mulatta , Masculino , Vincristina/sangue , Vincristina/metabolismoRESUMO
Vincristine concentration in serum from 1 min to 72 hr was measured by radioimmunoassay in 14 patients with cancers following i.v. bolus injection of vincristine sulfate at 0.45 to 1.30 mg/sq m. The pharmacokinetic data were analyzed by a nonlinear least-square regression program NONLIN. A three-compartmental open model fitted the raw data better than a two-compartmental model. The mean half-lives of the triphasic decay curves alpha, beta, and gamma were 1.9, 19.2, and 1359 min (22.6 hr), respectively. The apparent volume of the central compartment and the volume of distribution at steady state (Vdss) per 1.73 sq m body surface area were 4.1 and 167.6 liters, respectively. The plasma clearance was 141.9 ml/min/1.73 sq m, and the area under the concentration X time curve from 0 to infinity (AUC0 infinity) for 2 mg vincristine was 21,689 nM.min. Linear regression analysis of the data gave evidence for increasing plasma clearance at higher doses of vincristine. In patients with higher platelet counts, lower AUC0 infinity values were obtained, suggesting a possible interaction of vincristine with blood platelets. Our results, a large Vdss, a long biological half-life, and a low rate-limiting rate constant from Compartment 3 to the central compartment (k31), indicate an avid tissue binding and a slow drug release from the body tissues which may account for drug-related neurotoxicity.
Assuntos
Neoplasias/tratamento farmacológico , Vincristina/administração & dosagem , Adulto , Idoso , Relação Dose-Resposta a Droga , Feminino , Meia-Vida , Humanos , Injeções Intravenosas , Cinética , Masculino , Taxa de Depuração Metabólica , Pessoa de Meia-Idade , Doenças do Sistema Nervoso/induzido quimicamente , Contagem de Plaquetas , Análise de Regressão , Vincristina/efeitos adversos , Vincristina/sangueRESUMO
One-hundred thirty eligible patients with advanced colorectal carcinoma who had received no prior chemotherapy were randomized to either methyl-CCNU, 70 mg/m2 orally every 6 weeks on day 1, mitomycin C, 10 mg/m2 intravenously every 6 weeks on day 1, and 5-fluorouracil (5-FU), 400 mg/m2 intravenously weekly--(MMF)--or 5-FU, 600 mg/m2 intravenously weekly (5-FU). One hundred twenty-six patients are evaluable for response. Of 62 patients treated with MMF, one (2%) achieved complete remission, and three (5%) attained partial remission. Of 64 patients treated with 5-FU, two (3%) achieved complete remission, and eight (13%) attained partial remission. The median survival for patients receiving MMF was 9.5 months compared with 10.3 months for patients receiving 5-FU. The survival distributions for the two regimens were not significantly different, either unadjusted or adjusted for pretreatment characteristics. Performance status and lactic dehydrogenase (LDH) were both significantly associated with survival. Patients with liver metastases only and normal liver function tests had a median survival of 19.8 months and a 40% response rate. This randomized phase III trial did not show any therapeutic advantage for MMF compared to 5-FU therapy alone in advanced colorectal cancer. In addition, hematologic toxicity was significantly greater with the combination (MMF) regimen.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Colo/tratamento farmacológico , Fluoruracila/uso terapêutico , Neoplasias Retais/tratamento farmacológico , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/toxicidade , Ensaios Clínicos como Assunto , Esquema de Medicação , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/toxicidade , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Mitomicina , Mitomicinas/administração & dosagem , Semustina/administração & dosagemRESUMO
Thirty-three patients with advanced breast cancer were treated with a recombinant alpha interferon (rIFN-alpha 2). All patients were ambulatory (performance status greater than or equal to 50 Karnofsky scale) and almost all had received previous chemotherapy. Large intravenous dosages of 30 to 50 X 10(6) IU/m2 were given for five consecutive days every two to three weeks to 22 patients and smaller subcutaneous dosage of 2 X 10(6) IU/m2 three times a week to 11 patients. No complete or partial responses were seen. Two patients had stable disease and the remainder progressed. Flu-like syndromes were seen in all patients. Nausea, vomiting, and anorexia were frequent. Hypotension and confusion were noted in six and five patients, respectively. Life-threatening leukopenia was noted in two patients receiving intravenous dosage and thrombocytopenia was noted in one; no sepsis or bleeding complications were noted. In this study, a highly purified and biologically active rIFN-alpha 2 was not associated with activity in previously treated women with metastatic breast cancer.
Assuntos
Neoplasias da Mama/terapia , Interferon Tipo I/uso terapêutico , Adulto , Idoso , Neoplasias da Mama/patologia , Confusão/induzido quimicamente , DNA Recombinante , Esquema de Medicação , Avaliação de Medicamentos , Feminino , Humanos , Influenza Humana/induzido quimicamente , Injeções Intravenosas , Injeções Subcutâneas , Interferon Tipo I/administração & dosagem , Interferon Tipo I/efeitos adversos , Pessoa de Meia-Idade , Metástase Neoplásica , Recidiva Local de NeoplasiaRESUMO
Computed cranial tomographic scans were performed as part of the pretreatment evaluation and at six- to nine-month intervals posttreatment in 13 patients with small cell lung carcinoma. All patients received 3,000 rad of prophylactic cranial irradiation delivered over two weeks in ten treatment fractions in conjunction with multiagent chemotherapy. Posttreatment scans documented an extraordinarily high frequency of abnormalities including cerebral atrophy (100%), ventricular dilatation (70%), and decreased coefficient of absorption in the white matter (15%). Unexplained neurologic abnormalities developed in four of six patients living at least 15 months after institution of therapy. As the number of long-term survivors of this type of lung cancer increases, the need for prospective comprehensive neuropsychologic assessment to determine the clinical significance of these changes is needed.
Assuntos
Neoplasias Encefálicas/prevenção & controle , Encéfalo/diagnóstico por imagem , Carcinoma de Células Pequenas/terapia , Neoplasias Pulmonares/terapia , Lesões por Radiação/diagnóstico por imagem , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Atrofia/diagnóstico por imagem , Encéfalo/patologia , Encéfalo/efeitos da radiação , Neoplasias Encefálicas/secundário , Carcinoma de Células Pequenas/tratamento farmacológico , Carcinoma de Células Pequenas/secundário , Ventrículos Cerebrais/patologia , Terapia Combinada , Dilatação Patológica/diagnóstico por imagem , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Tomografia Computadorizada por Raios XRESUMO
The effect of adding the epipodophyllotoxin etoposide (VP-16-213) to a standard chemotherapy regimen for patients with extensive stage small-cell lung cancer was evaluated during a randomized trial. Chemotherapy consisted of vincristine, doxorubicin, and cyclophosphamide (VAC) alone or with etoposide (EVAC). Of 139 patients enrolled, 136 patients were eligible for study and all but five were evaluable for response. The overall objective response was 46% in the VAC group v 70% in the etoposide-treated group (P = .008) with complete response (CR) rates of 12% v 29%, respectively (P = .030). Although the time to the observation of disease progression was significantly longer in the group of patients receiving etoposide (9.6 v 6.5 months, P = .010), overall survival was similar; this was probably due to administration of other agents including etoposide at the time of VAC failure. However, there were noteworthy differences in long-term (greater than or equal to 2 year) survival. Whereas only four (6%) patients treated with VAC lived 2 years, 11 (16%) of the etoposide-treated group did so (P = .100). Two-year failure-free survival was attained in one (2%) of the VAC patients and eight (11%) of the patients treated with etoposide (P = .034). Long-term survivorship, heretofore usually reported in patients with limited stage disease after a variety of treatments, may be possible with this drug combination in the setting of extensive disease.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma de Células Pequenas/mortalidade , Ensaios Clínicos como Assunto , Ciclofosfamida/administração & dosagem , Dactinomicina/administração & dosagem , Doxorrubicina/administração & dosagem , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Podofilotoxina/administração & dosagem , Prognóstico , Distribuição Aleatória , Vincristina/administração & dosagemRESUMO
One hundred thirty-eight patients with recurrent or metastatic breast cancer were randomized to receive megestrol acetate 40 mg orally four times daily or tamoxifen 10 mg orally twice a day. Upon treatment failure patients were crossed over to the alternate treatment. Eligibility required that either the estrogen receptor (ER) or progesterone receptor (PR) be positive or that both values be unknown, and that the patients be at least 2 years post-spontaneous menopause or over 50 years of age. Pretreatment characteristics including performance status (PS), disease-free interval (DFI), receptor status, and prior treatment were similar for both groups. Only three patients had previous hormonal therapy while one third had prior chemotherapy. Objective response was determined using strict International Union Against Cancer (UICC) criteria. Seventeen of 61 patients achieved complete response (CR) or partial response (PR) on megestrol (28%) while 20 of 64 patients achieved CR or PR on tamoxifen (31%). Responses of skin and bone lesions were similar for both agents; however, more patients with visceral disease responded to tamoxifen. Response did not correlate with the level of ER or PR but was correlated with age. Both unadjusted and adjusted analysis of time to progression and adjusted analysis (for pretreatment variables) of survival showed significant differences favoring tamoxifen. Six of 44 patients (14%) crossed from megestrol to tamoxifen achieved CR or PR while only two of 38 patients (5%) crossed from tamoxifen to megestrol achieved response. Only one of the original patients randomized to megestrol remains on study, while 12 patients still remain on tamoxifen. These data indicate similar response rates for megestrol and tamoxifen; however, time to progression and overall survival significantly favor tamoxifen when used as first-line therapy in this trial.
Assuntos
Neoplasias da Mama/tratamento farmacológico , Megestrol/análogos & derivados , Tamoxifeno/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Ensaios Clínicos como Assunto , Feminino , Humanos , Megestrol/efeitos adversos , Megestrol/uso terapêutico , Acetato de Megestrol , Pessoa de Meia-Idade , Metástase Neoplásica , Distribuição Aleatória , Indução de Remissão , Tamoxifeno/efeitos adversosRESUMO
PURPOSE: To determine in a prospective randomized trial whether high-dose orally administered medroxy-progesterone acetate (MPA) was superior to tamoxifen in patients with recurrent or metastatic breast cancer who had received no prior endocrine therapy in either the adjuvant or advanced setting. PATIENTS AND METHODS: Patients initially received either tamoxifen 20 mg/d orally or MPA 1 g/d orally. At the time of disease progression, patients were crossed over to the other regimen. Eligibility required patients to be age > or = 18 years, performance status 0 to 3, and estrogen receptor (ER)- or progesterone receptor (PR)-positive or unknown. RESULTS: One hundred eighty-two eligible patients were entered and 166 were assessable for response. Complete plus partial response rates for tamoxifen and MPA were 17% and 34%, respectively (P = .01). Patients with bone metastases had a significantly higher partial response rate with MPA compared with tamoxifen (33% v 13%). Median time to treatment failure was 5.5 months for tamoxifen and 6.3 months for MPA (P = .48). The median survival duration was 24 months for tamoxifen and 33 months for MPA (P = .09). Multivariate analysis showed that treatment significantly influenced response rate, but not time to treatment failure or survival. After treatment failure following MPA, six of 42 patients (14%) treated with tamoxifen responded, compared with six of 49 (12%) treated with MPA following tamoxifen. Both agents were associated with minimal toxicity, but 35% of patients on MPA gained more than 20 lb as opposed to only 2% on tamoxifen. CONCLUSION: In this trial, initial treatment with MPA of endocrine-naive metastatic breast cancer patients was associated with a significantly higher response rate but not with improvement in time to treatment failure or survival, when compared with initial treatment with tamoxifen. Further randomized trials in patients with bone metastases are warranted to determine if high-dose progestin therapy is superior to tamoxifen in these patients.
Assuntos
Neoplasias da Mama/tratamento farmacológico , Acetato de Medroxiprogesterona/administração & dosagem , Tamoxifeno/administração & dosagem , Administração Oral , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/secundário , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Esquema de Medicação , Feminino , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Acetato de Medroxiprogesterona/efeitos adversos , Pessoa de Meia-Idade , Estudos Prospectivos , Análise de Regressão , Neoplasias de Tecidos Moles/tratamento farmacológico , Neoplasias de Tecidos Moles/secundário , Análise de Sobrevida , Tamoxifeno/efeitos adversosRESUMO
A phase 2 trial of vincristine infusion was conducted in a group of 21 patients with refractory multiple myeloma. Patients were generally heavily pretreated with radiotherapy and chemotherapy. Vincristine was given intravenously (IV) as a 0.5 mg bolus and followed immediately by infusion of 0.25 to 0.50 mg/m2/d for 5 days. Courses were repeated every 3 weeks in the absence of disease progression or prohibitive toxicity. Objective responses (partial) were noted in two patients (10%), both of whom were administered 0.5 mg/m2/d infusions. Response durations were brief (2.2 and 1.2 months). Toxicity consisted of neurotoxicity and myelosuppression. In addition to the occurrence of paresthesias and myalgias, ileus (two cases) and moderately severe loss of motor function (two cases) were observed. The mean lowest WBC count following treatment was 2.67 X 10(3)/microL v 3.96 X 10(3)/microL pretreatment (P = .008). The mean lowest platelet count was 75.0 X 10(3)/microL v 106.8 X 10(3)/microL pretreatment (P = .008). Vincristine infusion appears to have limited activity in the treatment of refractory multiple myeloma. Additionally, response durations were short lived and toxicity, both neurologic and hematologic, was appreciable.
Assuntos
Mieloma Múltiplo/tratamento farmacológico , Vincristina/uso terapêutico , Adulto , Idoso , Avaliação de Medicamentos , Feminino , Doenças Hematológicas/induzido quimicamente , Humanos , Infusões Parenterais , Obstrução Intestinal/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/patologia , Náusea/induzido quimicamente , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Vincristina/efeitos adversos , Vincristina/sangueRESUMO
The role of etoposide epipodophyllotoxin (VP-16-213) in a combined modality treatment program incorporating local chest irradiation and combination chemotherapy with cyclophosphamide, Adriamycin (Adria Laboratories, Columbus, Ohio), and vincristine has been evaluated in a randomized trial of 165 patients with small-cell lung cancer. The overall response rate (complete response [CR] plus partial response [PR]) was significantly greater in the VP-16-213 arm (85% v 64%, P = .005) primarily as a consequence of improved response in patients with extensive disease (85% v 38%, P = .002 and 30% v 8% for CR only, P = .045). No differences in the response rates were observed in limited disease. The duration of response (months) was greater in the VP-16-213 arm (8.6 v 7.0 overall and 14.4 v 11.5 for CR) but not significantly so. Median survival times (months) were consistently greater in the group receiving VP-16-213 when analyzed according to extent of disease and response (10.6 v 9.5 overall; 15.0 v 13.6 for limited disease; 9.0 v 6.7 for extensive disease; 18.5 v 16.2 for CR overall; and 18.6 v 16.1 for CR in limited disease); the results were not statistically significant. The median survival of extensive disease patients attaining a CR was 15.3 months (range 3.2 to 34.3 + months) in the VP-16-213 arm and 7.4+ and 8.1+ months for the two patients with CR in the other group. Anemia and leukopenia occurred to a greater degree in the four-drug regimen, but no unusual or significant compounding toxicity (ie, neurotoxicity) was observed otherwise. Further investigation of this agent in combination chemotherapy programs for small-cell lung cancer appears to be warranted.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma de Células Pequenas/terapia , Etoposídeo/administração & dosagem , Neoplasias Pulmonares/terapia , Podofilotoxina/análogos & derivados , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Terapia Combinada , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Vincristina/administração & dosagemRESUMO
Forty-four evaluable patients with untreated acute myelogenous leukemia received twice-daily subcutaneous injections of low-dose ara-C (10 mg/m2) for less than or equal to 42 days. The median age was 72 years (range 53-87); 42 of 44 patients were greater than or equal to age 60. Ten patients (23%) had complete responses with a median duration of 9.9 months. Median survival was 3 months (range 0.6-31.2+) for all patients, and 19.5 (range 7.9-31.2+) for patients who attained complete responses. Cytoreduction occurred slowly with low-dose ara-C and five of ten patients who achieved complete remission did not develop marrow aplasia. Toxicity was predominantly related to infections associated with granulocytopenia. Nonhematologic toxicity was limited. Low-dose ara-C as used in this trial results in a complete response rate and a duration of response similar to those achieved with other treatments in elderly patients, but with reduced toxicity.
Assuntos
Envelhecimento , Citarabina/administração & dosagem , Leucemia Mieloide Aguda/tratamento farmacológico , Idoso , Ensaios Clínicos como Assunto , Citarabina/efeitos adversos , Citarabina/uso terapêutico , Esquema de Medicação , Feminino , Granulócitos/efeitos dos fármacos , Hemorragia/induzido quimicamente , Humanos , Infecções/induzido quimicamente , Injeções Subcutâneas , Leucemia Mieloide Aguda/complicações , Leucemia Mieloide Aguda/fisiopatologia , Leucopenia/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Indução de Remissão , Trombocitopenia/induzido quimicamenteRESUMO
Forty patients with high risk myelodysplastic syndromes--refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, or chronic myelomonocytic leukemia--were treated with subcutaneous low dose cytosine arabinoside, 10 mg/m2 twice daily for up to 42 days. In 38 evaluable patients there were nine (24%) complete and four (11%) partial responses. Response was associated with symptomatic improvement and resolution of the need for red cell and platelet transfusions. The median duration of complete response was 9.8 months (range, 2.4-17.9); these patients had a median survival of 15.7 months (range, 6.0-22.7). Toxicities were predominantly those associated with pancytopenia, i.e., infection and hemorrhage.
Assuntos
Citarabina/uso terapêutico , Síndromes Mielodisplásicas/tratamento farmacológico , Adulto , Idoso , Infecções Bacterianas/etiologia , Contagem de Células Sanguíneas , Medula Óssea/patologia , Citarabina/efeitos adversos , Esquema de Medicação , Feminino , Hemorragia/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/sangue , Síndromes Mielodisplásicas/complicações , Indução de RemissãoRESUMO
Four patients with angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) had lymphograms that did not show a consistent radiographic pattern. Instead, a spectrum of radiologic changes ranging from a moderate increase in lymph node size with slight "foaminess" to total nonopacification was observed. One patient with this disorder had gray-scale echograms that showed enlarged anechoic lymph nodes. The findings in this small group of patients with AILD are indistinguishable from the radiologic and echographic changes seen in malignant lymphoma.
Assuntos
Linfografia , Linfoma/diagnóstico , Ultrassonografia , Idoso , Biópsia , Erros de Diagnóstico , Feminino , Humanos , Linfonodos/patologia , Ativação Linfocitária , Linfoma/diagnóstico por imagem , Linfoma/imunologia , Linfoma/patologia , Masculino , Pessoa de Meia-IdadeRESUMO
A patient with pancreatic carcinoma and a choledochal T tube was given tritiated vincristine sulfate ([3H]-VCR) intravenously. Peak biliary excretion occurred in 2 to 4 hr and this sample contained 9.7% of the injected radioactivity. The first 24-hr bile sample contained 21.7% of the dose and 76.4% of the cumulative 72-hr biliary excretion. During a 3-day period of observation, 4.2%, 45.6%, and 49.6% of the excreted radiolabel was present in the feces, urine, and bile, respectively. Products of VCR metabolism and decomposition appeared in the bile rapidly; only 46.5% of the drug was present in the parent form in the 2-hr collection. Since significant amounts of these products were also identified in control specimens of bile, blood, plasma, and buffer alone after brief periods of incubation, the origin and nature of the species appearing in the bile remain unclear. Observing the fecal route to be the major source of elimination of radiolabel following intravenous injection of [3H]-VCR in our patients previously, we now conclude the biliary system to be the principal route of excretion of VCR and its products. Hepatic dysfunction might therefore alter elimination kinetics and increase the exposure to VCR and its products which might augment toxicity and require dose modification.
Assuntos
Bile/metabolismo , Vincristina/metabolismo , Biotransformação , Humanos , Cinética , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/metabolismoRESUMO
Over the past 10 years, four clinical trials have been conducted with a total of 528 patients with previously untreated small-cell lung cancer. Trials I to III were randomized phase III studies testing the value of prophylactic cranial irradiation, immunotherapy, and etoposide, respectively. They were done in the setting of combined modality treatment with the same local chest radiotherapy (3,000 rad in 10 fractions) and combined agent chemotherapy using a nucleus of CAV (cyclophosphamide, doxorubicin, vincristine). Trial IV was a pilot study evaluating sequential hemibody radiotherapy in a combined modality treatment program with CAV. Overall, the best treatment results to date have been observed following the combination of etoposide with CAV in trial III, particularly for patients with extensive disease. This combination with or without other agents also appears to be a common component of many trials that have reported particularly good survival results in this disease.
Assuntos
Carcinoma de Células Pequenas/terapia , Neoplasias Pulmonares/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ensaios Clínicos como Assunto , Terapia Combinada , Humanos , Prognóstico , Indução de RemissãoRESUMO
One hundred twenty-four patients with recurrent or metastatic breast cancer were randomized to receive megestrol acetate 40 mg orally, four times daily, or tamoxifen 10 mg orally twice daily. If therapy failed patients were crossed over to the alternate treatment. Eligibility required that either the estrogen or progesterone receptor be positive or that both values be unknown, and that patients be at least 2 years postspontaneous menopause or over 50 years of age. Pretreatment characteristics were similar for both groups. Three patients had had previous hormonal therapy while one third had had chemotherapy. Objective response for evaluable patients based on strict UICC criteria was 29% with megestrol acetate and 31% with tamoxifen. Responses in patients with bone and soft tissue disease were similar for both regimens; however, 7 of 19 (37%) patients with visceral disease responded to tamoxifen but none of 18 (0%) responded to megestrol acetate. Response did not correlate with amount of estrogen or progesterone receptor. Unadjusted analysis of time to progression and survival showed no significant differences between regimens. With adjustment for pretreatment characteristics, patients on tamoxifen had a statistically significant prolongation of both of these parameters. Crossover data show 3 of 24 patients responding to tamoxifen after failure on megestrol acetate and 1 of 24 responding to megestrol acetate after failure on tamoxifen. However, crossover data should be viewed cautiously, as patients who are currently responding to initial treatment are those who would be most likely to respond to crossover therapy.
Assuntos
Neoplasias da Mama/tratamento farmacológico , Megestrol/análogos & derivados , Tamoxifeno/uso terapêutico , Idoso , Neoplasias da Mama/mortalidade , Ensaios Clínicos como Assunto , Feminino , Humanos , Megestrol/efeitos adversos , Megestrol/uso terapêutico , Acetato de Megestrol , Pessoa de Meia-Idade , Tamoxifeno/efeitos adversosRESUMO
Neurotoxicity is the principal limiting side effect of the widely used antitumor agent, vincristine. Following evaluation of glutamic acid as a potential modifier of vincristine toxicity in preclinical studies in mice and a preliminary clinical trial, a prospective, double-blind, placebo-controlled, randomized trial was conducted by the Piedmont Oncology Association. Of 87 patients entered into the study, 84 were evaluable, including 42 patients who were randomly assigned to receive vincristine 1.0 mg/m2 weekly for six doses and 42 patients who were assigned to receive glutamic acid 500 mg orally three times daily plus vincristine. The following neurotoxic signs and symptoms were evaluated before each dose of vincristine: reflex changes, paresthesias, constipation, strength, and mental changes. Loss of the Achilles tendon reflex, an objective parameter, was noted in 19 percent of patients receiving glutamic acid and 42 percent of control subjects (p = 0.03). Development of moderate to severe paresthesias, a subjective parameter, occurred in 19 percent of the glutamic acid group and 36 percent of the placebo group (p = 0.09). Overall moderate neurotoxicity (6 units or more), determined by adding the grade of each neurotoxic parameter for the weekly clinic visit in which maximum neurotoxicity occurred, was observed in 21 percent of patients receiving glutamic acid and 43 percent of those in the control group (p = 0.04). Hematologic and gastrointestinal side effects occurred with similar frequency in the two groups. The administration of glutamic acid has decreased vincristine-induced neurotoxicity without any attendant side effects.
Assuntos
Glutamatos/administração & dosagem , Sistema Nervoso/efeitos dos fármacos , Vincristina/efeitos adversos , Adulto , Idoso , Neoplasias da Mama/tratamento farmacológico , Ensaios Clínicos como Assunto , Constipação Intestinal/induzido quimicamente , Método Duplo-Cego , Feminino , Ácido Glutâmico , Humanos , Processos Mentais/efeitos dos fármacos , Pessoa de Meia-Idade , Parestesia/induzido quimicamente , Estudos Prospectivos , Distribuição Aleatória , Reflexo/efeitos dos fármacos , Vincristina/administração & dosagem , Vincristina/uso terapêuticoRESUMO
Twenty-four patients with limited disease small cell lung cancer (SCLC) were treated with sequential hemibody irradiation (SHB) integrated into a conventional chemotherapy-local radiotherapy (LRT) program. Among 23 evaluable patients, 12 (52%) attained a complete response (CR) and 8 (35%) attained a partial response for an overall major response rate of 87%. The median time since study entry is 29 months. Durations of response are 9.9 months for all patients and 16.5 months for patients who achieved a CR. The primary site was the predominant area of recurrence. The median survival is 13.2 months for all patients and 23.2 months for the 12 patients who attained a CR. Myelosuppression, especially thrombocytopenia, was the major toxicity. Acute radiation toxicities and subacute pneumonitis previously associated with hemibody radiotherapy were well controlled or prevented using the current dose, premedication, and shielding techniques. This integrated program of systemic therapies with SHB and combination chemotherapy plus LRT is feasible for limited disease SCLC; it may prolong survival in patients who attain a CR but compared to similar programs without hemibody irradiation, there was no improvement in overall response rate, response duration, or survival.