RESUMEN
Sixty adult patients with incompletely excised low-grade gliomas were randomly assigned to receive radiotherapy (55 Gy over a total of 6 1/2 to 7 weeks) either alone or with 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU; 100 mg/sq m every 6 weeks). Pathological review showed that six patients were ineligible for the study. Evaluation of patient age, extent of surgery, tumor grade, and performance status showed no significant differences between the treatment arms. The response rate, as judged by the disappearance or reduction in size of the tumor on computerized tomography scans, was 79% for radiation therapy alone versus 54% for irradiation plus CCNU. The median survival time was 4.45 years for all patients, with no significant difference between treatment arms (p = 0.7). For the group as a whole, patient age and performance status were the most important prognostic parameters. The majority of patients receiving chemotherapy experienced moderate hematological toxicity. This study demonstrates that CCNU chemotherapy does not improve the results of radiation therapy in the treatment of incompletely excised low-grade gliomas.
Asunto(s)
Neoplasias Encefálicas/terapia , Glioma/terapia , Lomustina/uso terapéutico , Adulto , Anciano , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/mortalidad , Terapia Combinada , Femenino , Glioma/diagnóstico por imagen , Glioma/mortalidad , Humanos , Masculino , Persona de Mediana Edad , Cuidados Posoperatorios , Estudios Prospectivos , Radioterapia/efectos adversos , Tasa de Supervivencia , Tomografía Computarizada por Rayos XRESUMEN
From 1981 through 1985 the Southwest Oncology Group (SWOG) conducted a study evaluating the natural history and the effectiveness of standard therapy in those patients with leptomeningeal carcinomatosis from non-hematologic malignancies. Twenty-six patients were evaluated for the effectiveness of treatment; those who responded to therapy by one month exhibited a median additional survival of 5.7 months and those who were not responders at one month exhibited a median additional survival of 1.8 months. We were unable to identify pre-treatment clinical characteristics which would predict for a favorable response to therapy. Aggressive treatment in some patients may be indicated, as those patients who respond to treatment may have a survival benefit. The overall prognosis in this patient group remains exceedingly poor.
Asunto(s)
Neoplasias Meníngeas/secundario , Metotrexato/uso terapéutico , Terapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Inyecciones Espinales , Neoplasias Meníngeas/tratamiento farmacológico , Neoplasias Meníngeas/radioterapia , Metotrexato/administración & dosificación , Persona de Mediana EdadRESUMEN
Three patients treated with bilateral subcutaneous mastectomies and implants for fibrocystic disease or carcinoma in situ subsequently developed invasive breast carcinoma. These cases emphasize that subcutaneous mastectomy does not prevent the development of breast cancer. If the circumstances in an individual patient justify prophylactic mastectomy, then the appropriate procedure would seem to be total mastectomy, which would accomplish thorough removal of all breast tissue, the subareolar region, and the nipple. Subcutaneous mastectomy for the patient who is likely to harbor occult invasive disease seems particularly inappropriate. As a means to reduce the risk of breast cancer, the procedure is unproved and must be considered an experimental therapeutic approach.
Asunto(s)
Neoplasias de la Mama/prevención & control , Carcinoma in Situ/cirugía , Carcinoma Intraductal no Infiltrante/cirugía , Enfermedad Fibroquística de la Mama/cirugía , Mastectomía/métodos , Adenocarcinoma/patología , Adenocarcinoma/cirugía , Adulto , Neoplasias de la Mama/patología , Neoplasias de la Mama/cirugía , Carcinoma/patología , Carcinoma/cirugía , Carcinoma in Situ/patología , Carcinoma Intraductal no Infiltrante/patología , Femenino , Enfermedad Fibroquística de la Mama/patología , Humanos , RiesgoRESUMEN
A phase II study using vindesine (3 mg/m2 by slow intravenous push at seven to 14 day intervals) was carried out in 42 patients with metastatic melanoma. There was one complete remission (2.5%) of greater than 12 months duration; seven partial remissions (17.5%) of two, three, three, four, five, six and eight months duration; 11 with no change (27.5%) of one to 10 months duration; and 21 (52.5%) patients with increasing disease. Toxicity included neutropenia, neurotoxicity, phlebitis and cellulitis at the site of injection, alopecia, fever and chills, myalgias, and gastrointestinal toxicity. It was concluded that vindesine does have activity in some patients with metastatic malignant melanoma. Further studies in previously untreated patients are warranted.
Asunto(s)
Neoplasias Pulmonares/tratamiento farmacológico , Melanoma/tratamiento farmacológico , Neoplasias Cutáneas/tratamiento farmacológico , Vinblastina/análogos & derivados , Adulto , Anciano , Evaluación de Medicamentos , Femenino , Enfermedades Gastrointestinales/inducido químicamente , Humanos , Leucopenia/inducido químicamente , Neoplasias Pulmonares/secundario , Metástasis Linfática , Masculino , Melanoma/secundario , Persona de Mediana Edad , Enfermedades del Sistema Nervioso/inducido químicamente , Neoplasias Cutáneas/secundario , Trombocitopenia/inducido químicamente , Vinblastina/efectos adversos , Vinblastina/uso terapéutico , VindesinaRESUMEN
One hundred and fifteen eligible patients with histologically verified malignant gliomas (astrocytoma grade III-IV) were randomized to receive either radiotherapy 6 000 rads/7 week plus CCNU 130 mg/M2 every 6 weeks (treatment 1) or radiotherapy 6 000 rads/7 weeks plus CCNU 75 mg/M2 day 1 plus procarbazine 100 Mg/m2 days 1-14 every 6 weeks (treatment 2) within 4 weeks following surgical resection. The response rates showed no statistically significant differences between treatment 1 CR/PR - 24/17% and treatment 2 CR/PR - 14/14% (P-value = 0.31). The median survival was also not significantly different: 55 and 50 weeks for treatments 1 and 2, respectively. The most important prognostic parameter identified was age with younger patients showing higher response rates and longer survival. Patients' performance status was also a useful prognostic parameter for response and survival. Neither the extent of surgical resection nor the tumor grade correlated significantly with the outcome. Further studies are needed to identify active chemotherapeutic agents for the treatment of brain tumors.
Asunto(s)
Neoplasias Encefálicas/terapia , Glioblastoma/terapia , Lomustina/uso terapéutico , Procarbazina/uso terapéutico , Radioterapia de Alta Energía , Neoplasias Encefálicas/cirugía , Terapia Combinada , Quimioterapia Combinada , Femenino , Glioblastoma/cirugía , Humanos , Lomustina/efectos adversos , Masculino , Persona de Mediana Edad , Procarbazina/efectos adversos , PronósticoRESUMEN
Phase II studies utilizing VP-16-213 in the treatment of 56 patients with malignant lymphoma and 29 patients with malignant melanoma were carried out by the Southwest Oncology Group. All patients had received extensive prior therapy. The initial dose of VP-16-213 administered was 45 mg/m2 by iv infusion over 30-60 minutes on Days 1-5 every 3 weeks but, because, of severe myelosuppression in the lymphoma group, the dose was subsequently reduced to 35 mg/m2. Only three partial regressions lasting 6, 2, and 1 months were noted in 17 patients with Hodgkin's disease. No favorable responses were noted in 35 patients with non-Hodgkin's lymphoma including 16 with the diffuse histiocytic type. No responses were noted in patients with melanoma. The major toxic effect was myelosuppression. VP-16-213 appears to lack significant effectiveness in these previously treated disease.
Asunto(s)
Etopósido/uso terapéutico , Linfoma/tratamiento farmacológico , Melanoma/tratamiento farmacológico , Podofilotoxina/análogos & derivados , Adulto , Evaluación de Medicamentos , Etopósido/efectos adversos , Femenino , Enfermedad de Hodgkin/tratamiento farmacológico , Humanos , MasculinoRESUMEN
A phase II study utilizing 5-azacytidine in the treatment of patients with solid tumors was carried out by the Southwest Oncology Group (SWOG-7208). Of 214 patients entered in the study 191 were eligible and 167 were evaluable. While initially they received 225 mg/m2 iv on Days 1--5 every 3 weeks because of toxicity the dose was subsequently reduced to 175mg/m2 and later to 150 mg/m2. Five partial regressions, 2.6% of the eligible patients and 3% of the evaluable patients, lasting from 28 to 77 days were observed. Sixteen patients 8.4% of the eligible patients and 9.6% of the evaluable patients, had no significant change in their disease for 39--255 days. The major toxicities were myelosuppressive and gastrointestinal with 13 deaths attributable to drug toxicity: 11 due to sepsis and two due to cerebral hemorrhage. 5-Azacytidine induced few favorable responses; those that did occur usually were of poor quality and short duration and were associated with significant toxicity.
Asunto(s)
Azacitidina/uso terapéutico , Neoplasias/tratamiento farmacológico , Azacitidina/efectos adversos , Recuento de Células Sanguíneas , Relación Dosis-Respuesta a Droga , Evaluación de Medicamentos , Enfermedades Gastrointestinales/inducido químicamente , Enfermedades Hematológicas/inducido químicamente , HumanosRESUMEN
DTIC was one of the first of several new agents evaluated by the Southwest Oncology Group (SWOG) and the M.D. Anderson Hospital and Tumor Institute (MDAH) in the therapy of adult patients with metastatic sarcomas. It yielded an overall response rate of 17%. This is similar to that seen in a review of 138 patients who represent the total number reported in either published or unpublished data. The subsequent addition of DTIC to adriamycin in several studies carried out at the MDAH and in the SWOG has increased the complete and partial remission rate over that seen with adriamycin alone, and more importantly has increased remission duration and survival. DTIC is currently used in combination with adriamycin in the first-line therapy of patients with metastatic sarcomas and should be considered for patients who have relapsed on primary therapy not including DTIC.
Asunto(s)
Dacarbazina/uso terapéutico , Leiomiosarcoma/tratamiento farmacológico , Sarcoma/tratamiento farmacológico , Triazenos/uso terapéutico , Ensayos Clínicos como Asunto , Doxorrubicina/uso terapéutico , Evaluación de Medicamentos , Quimioterapia Combinada , Humanos , Metástasis de la Neoplasia , Vincristina/uso terapéuticoRESUMEN
Ftorafur, a furanyl analog of 5-fluorouracil (5-FU), is reported to be five to six times less toxic and possibly more effective in cancer of the breast and colon than 5-FU. The drug was synthesized, formulated, and utilized in toxicologic studies, and then in 24 patients with advanced incurable malignancies. When Ftorafur is given by intravenous push, it results in immediate flushing, dizziness, nausea, retching, and in some cases transient hypotension. These immediate side effects are largely eliminated by administering the drug slowly by infusion. In patients, 60 mg/kg of Ftorafur given i.v. daily for up to 10 days resulted in mild toxicity. However, 80 mg/kg given i.v. daily for 7 days resulted in severe toxicity, with nausea, vomiting, stomatitis, leukopenia, and thrombocytopenia. These studies confirm those of the Russian investigators as to toxicity and dosage, even with a different method of administration more convenient for therapy. Phase II studies are presently being carried out to compare the effectiveness of Ftorafur and 5-FU.
Asunto(s)
Fluorouracilo/análogos & derivados , Adulto , Anciano , Animales , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/efectos adversos , Fluorouracilo/uso terapéutico , Humanos , Inyecciones Intravenosas , Masculino , Ratones , Persona de Mediana Edad , Neoplasias/tratamiento farmacológicoRESUMEN
In March of 1972, the Southwest Oncology Group initiated a Phase II study, No. 7200, utilizing methyl-CCNU in the treatment of patients with solid tumors and lymphomas. Initially, they received 200 mg/m2 orally as a single dose every 6 weeks. The dose was subsequently reduced in poor-risk patients to 150 mg/m2. There were 69 responses noted in 675 evaluable patients (10%). The highest response rates were noted in patients with Hodgkin's disease (13/31, 35%), malignant gliomas of the brain (8/29, 28%), anaplastic carcinomas of the lung (5/20, 25%), and squamous cell carcinomas of the head and neck (5/29, 17%). Squamous cell tumors appeared to be more responsive than adenocarcinomas (15% vs. 5%, respectively). Hematologic toxicity was cumulative, and was influenced by dose and prior treatment. There appeared to be no cross-resistance in patients previously treated with alkylating agents. Methyl-CCNU is an active antineoplastic agent. Further studies are indicated in order to determine relative effectiveness.
Asunto(s)
Antineoplásicos/uso terapéutico , Neoplasias/tratamiento farmacológico , Compuestos de Nitrosourea/uso terapéutico , Adenocarcinoma/tratamiento farmacológico , Administración Oral , Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Neoplasias Encefálicas/tratamiento farmacológico , Carcinoma de Células Escamosas/tratamiento farmacológico , Ciclohexanos/administración & dosificación , Ciclohexanos/análogos & derivados , Ciclohexanos/uso terapéutico , Evaluación de Medicamentos , Resistencia a Medicamentos , Glioma/tratamiento farmacológico , Cabeza , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Enfermedad de Hodgkin/tratamiento farmacológico , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Linfoma/tratamiento farmacológico , Compuestos de Nitrosourea/administración & dosificación , Compuestos de Nitrosourea/efectos adversosRESUMEN
BCNU, hydroxyurea, and imidazole carboxamide (DTIC) were administered to 89 patients with disseminated malignant melanoma. A response rate of 27% was observed. The addition of vincristine in another 89 patients did not significantly improve the response rate (30%). This includes patients who died during or after one course of therapy (less than 28 days). If the early deaths are not considered, the over-all response rate was 38%. (he best responses occurred in patients with skin, lung, and/or lymph node involvement. Liver and brain involvement heralded poor responses. This response rate appeared to be independent of age, sex or previous therapy. Moderate and severe toxicity, predominantly nausea and vomiting, was noted in most patients. The median survival for all evaluable patients was 17 months, and was independent of the regimen used.