RESUMO
Anaplastic thyroid carcinoma is a rare, lethal disease with no effective systemic therapies. Preclinical studies demonstrated antineoplastic activity of paclitaxel. This prompted a prospective phase 2 clinical trial to determine activity of paclitaxel against anaplastic thyroid carcinoma in patients with persistent or metastatic disease despite surgery or local radiation therapy. Twenty patients, entered through 6 of 12 study sites, were treated with 96-hour continuous infusion paclitaxel every 3 weeks for 1 to 6 cycles; the first 7 patients received 120 mg/m2 per 96 hours and the rest received 140 mg/m2 per 96 hours. Total responses to therapy were assessed using modified criteria with response durability acceptable at 2 or more weeks, due to the exceedingly rapid growth rate of this tumor. Plasma samples were obtained for pharmacokinetic analyses. Off-protocol, data showed that 9 patients were later treated with 225 mg/m2 paclitaxel as weekly 1-hour infusions. Nineteen evaluable patients demonstrated a 53% total response rate (95% confidence interval, 29%-76%) with one complete response and nine partial responses (including one off protocol). Results of historical review off-protocol showed 2 of 7 patients, with prior partial responses to the 96-hour infusion, had subsequent partial responses to weekly treatment and 1 of 2 prior nonresponders gained a partial response to weekly therapy. No toxicities greater than grade 2 were seen with 96-hour infusions, while peripheral neuropathy (up to grade 3) was most common with postprotocol weekly infusions. Paclitaxel appears to be the only agent with significant clinical systemic activity against anaplastic thyroid carcinoma; however, it is not capable of altering the lethality of this malignancy, suggesting the need for additional therapeutic innovations. Decreased time intervals between paclitaxel infusions may be more efficacious.
Assuntos
Carcinoma/tratamento farmacológico , Paclitaxel/uso terapêutico , Neoplasias da Glândula Tireoide/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Paclitaxel/farmacocinética , Taxa de Sobrevida , Neoplasias da Glândula Tireoide/mortalidade , Neoplasias da Glândula Tireoide/patologia , Resultado do TratamentoRESUMO
Concern is growing about the ability of categorical medicine residency programs, structured within academic health centers, to provide balanced, progressive, postgraduate internal medicine education. Detrimental factors, including over-representation of critically ill patients, shortened length of hospitalization, stress, discontinuity between undergraduate and graduate training, rotational assignments driven by hospital service imperatives, and total costs, may all negatively affect internal medicine residency education. Therefore, an experimental accelerated internal medicine (AIM) curriculum combining 3 years of undergraduate with 3 years of graduate internal medicine education has been initiated by the Department of Medicine and the College of Medicine at the University of Kentucky. After completion of the third year and during the first 13 months of the AIM curriculum, selected students are rotated through an integrated series of educational experiences that incorporate all of the requirements for graduation from medical school and progressively advance the students' skills, knowledge, and responsibilities to that of a second-year resident. Thereafter, the curriculum is similar to that of the categorical residents, except that more ambulatory care and off-site rotations are interspersed to better provide the educational experiences representative of the practice of internal medicine. Evaluations of the first groups of AIM residents indicate that their performance has equaled that of the control residents who graduated after 4 years from the College of Medicine. Furthermore, the AIM residents report general acceptance by their fellow residents and attending physicians and report no undue stress in making the transition.
Assuntos
Currículo , Educação de Graduação em Medicina/organização & administração , Medicina Interna/educação , Internato e Residência/organização & administração , Custos e Análise de Custo , Educação de Graduação em Medicina/economia , Internato e Residência/economia , Kentucky , Licenciamento em Medicina , Critérios de Admissão Escolar , Fatores de TempoAssuntos
Síndrome da Imunodeficiência Adquirida , Ética Médica , Revelação da Verdade , Síndrome da Imunodeficiência Adquirida/complicações , Síndrome da Imunodeficiência Adquirida/transmissão , Confidencialidade , Família , Hepatite B/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Princípios Morais , RiscoAssuntos
Adenocarcinoma/tratamento farmacológico , Cisplatino/administração & dosagem , Neoplasias do Colo/tratamento farmacológico , Neoplasias Retais/tratamento farmacológico , Cisplatino/efeitos adversos , Cisplatino/uso terapêutico , Ensaios Clínicos como Assunto , Feminino , Doenças Hematológicas/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Náusea/induzido quimicamenteAssuntos
Adenocarcinoma/tratamento farmacológico , Antraquinonas/uso terapêutico , Antineoplásicos/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Adulto , Idoso , Agranulocitose/induzido quimicamente , Antraquinonas/efeitos adversos , Antineoplásicos/efeitos adversos , Ensaios Clínicos como Assunto , Avaliação de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , MitoxantronaAssuntos
Antraquinonas/uso terapêutico , Antineoplásicos/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Adulto , Idoso , Agranulocitose/induzido quimicamente , Antraquinonas/efeitos adversos , Antineoplásicos/efeitos adversos , Ensaios Clínicos como Assunto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , MitoxantronaRESUMO
A Phase I-II study of razoxane (ICRF-159) and doxorubicin was undertaken in 34 adults with advanced gastrointestinal carcinoma. Three dose schedules were studied; weekly razoxane at 600 mg/m2 orally plus doxorubicin 60 mg/m2 every 3 weeks, razoxane at 300 mg/m2 plus doxorubicin 60 mg/m2, and weekly razoxane 300 mg/m2 plus doxorubicin 35 mg/m2 every 3 weeks. This combination produced moderate to severe granulocytopenia in 24 patients including granulocytopenia less than or equal to 500/mm3 in 15. The granulocytopenia occurred regardless of prior chemotherapy and regardless of dose schedule employed. Two septic deaths were recorded but no responses. Further evaluation of this combination is not recommended.
Assuntos
Adenocarcinoma/tratamento farmacológico , Neoplasias Gastrointestinais/tratamento farmacológico , Piperazinas/uso terapêutico , Razoxano/uso terapêutico , Agranulocitose/induzido quimicamente , Avaliação de Medicamentos , Humanos , Razoxano/efeitos adversosRESUMO
Thirty-three patients with advanced colorectal adenocarcinoma were treated with daily Anguidine i.v. 5 mg/m2 X 5 for 3 weeks. The patients were stratified into two groups: prior chemotherapy and no prior chemotherapy. No responses were noted. Major toxicities were hypotension and fever.
Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Neoplasias do Colo/tratamento farmacológico , Neoplasias Retais/tratamento farmacológico , Sesquiterpenos/uso terapêutico , Tricotecenos/uso terapêutico , Antineoplásicos Fitogênicos/efeitos adversos , Avaliação de Medicamentos , Febre/induzido quimicamente , Humanos , Hipotensão/induzido quimicamente , Tricotecenos/efeitos adversosRESUMO
One hundred four patients with advanced colon carcinoma were treated with mitoxantrone 5 mg/m2 I.V. weekly. The patients were stratified into two groups: prior chemotherapy and no prior chemotherapy. Only one partial response was noted in the prior treatment category.
Assuntos
Antraquinonas/uso terapêutico , Antineoplásicos/uso terapêutico , Neoplasias do Colo/tratamento farmacológico , Neoplasias Retais/tratamento farmacológico , Antraquinonas/efeitos adversos , Antineoplásicos/efeitos adversos , Avaliação de Medicamentos , Humanos , Mitoxantrona , Metástase NeoplásicaRESUMO
Biopsy specimens from 14 patients with oat cell carcinoma of the lung metastatic to bone marrow and from one patient with a localized tumor were examined for evidence of phagocytic activity by tumor cells. Phagocytic activity was observed in tumor cells in 90 per cent of the bone marrow biopsy specimens, 90 per cent of the cytology specimens, and 70 per cent of the biopsy specimens of other tissues. The cell most often phagocytosed was the leukocyte. Seventeen other tumors metastatic to bone marrow were studied and only one evidenced phagocytic activity.
Assuntos
Carcinoma de Células Pequenas/imunologia , Carcinoma de Células Pequenas/fisiopatologia , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/fisiopatologia , Doenças da Medula Óssea/imunologia , Doenças da Medula Óssea/fisiopatologia , Carcinoma de Células Pequenas/secundário , Humanos , Metástase Neoplásica , Neoplasias/fisiopatologia , FagocitoseRESUMO
A phase I evaluation of a weekly schedule of anguidine was undertaken as an alternative to the present continuous daily schedules. The dose ranged from 1.5 to 7.5 mg/m2 given as an infusion over 3 hours. No myelosuppression was noted at any dose level. The toxic effects included nausea and vomiting, hypotension, CNS symptoms (confusion, hallucinations, and psychomotor seizures), chills, fever, and diarrhea. A dose of 5 mg/m2 of anguidine produced acceptable toxicity.
Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Neoplasias/tratamento farmacológico , Sesquiterpenos/administração & dosagem , Tricotecenos/administração & dosagem , Antineoplásicos Fitogênicos/toxicidade , Encéfalo/efeitos dos fármacos , Esquema de Medicação , Avaliação de Medicamentos , Febre/induzido quimicamente , Humanos , Hipotensão/induzido quimicamente , Infusões Parenterais , Tricotecenos/toxicidade , Vômito/induzido quimicamenteRESUMO
195mPlatinum cis-dichlorodiammineplatinum(II) (195mPt cis-DDP) was injected iv with furosemide or mannitol into male Sprague-Dawley rats. The effect of such a diuresis on the distribution, excretion, and retention of cis-DDP was measured. The mannitol-treated animals had a significant increase in the urinary excretion of 196mPt over control animals for the first five 15-minute collection times and for the 24-hour cumulative urine for the 0.01-mg/kg dose. At the 6-mg/kg dose, only the first three 15-minute and 24-hour cumulative urine collections were significant. This increased excretion, however, did not affect tissue or blood concentrations of this agent. Furosemide did not affect the excretion of 195mPt. A biliary excretion of 195mPt given as 195mPt cis-DDP is documented. The excretion is biphasic, with a rapid phase followed by a slower protracted phase. Forced diuresis, if it affords renal protection, does so during the first 90 minutes of urinary excretion.
Assuntos
Cisplatino/administração & dosagem , Diurese , Platina/metabolismo , Animais , Bile/metabolismo , Cisplatino/metabolismo , Cisplatino/urina , Interações Medicamentosas , Furosemida/administração & dosagem , Injeções Intravenosas , Rim/efeitos dos fármacos , Masculino , Manitol/administração & dosagem , Radioisótopos , Ratos , Distribuição TecidualRESUMO
Involvement of the central nervous system is a rare complication of infectious mononucleosis. Isolated cranial nerve palsy is the least reported neurologic complication. We report a second case of hypoglossal nerve palsy associated with infectious mononucleosis, and review 20 other reported cases of cranial nerve palsies. Any cranial nerve may be involved. The onset of the palsy usually follows the diagnosis and clinical presentation of infectious mononucleosis. The prognosis for a complete recovery is excellent, although recovery may be protracted. The use of steroids does not appear to be etiologic, nor beneficial or deleterious in treatment.