RESUMO
BACKGROUND: Combination chemotherapy is associated with improved outcomes in trials of selected fit patients with advanced colorectal cancer (acrc). For older or less-fit patients, combination chemotherapy is associated with greater toxicity and less benefit. Capecitabine monotherapy is a reasonable option for those patients, but the optimal dose remains controversial. METHODS: A multicentre phase i/ii trial of reduced-dose capecitabine (2000 mg/m2, days 1-14 every 21 days) was conducted in 221 patients representing one or more of the following subsets: age greater than 65 years (n = 167), Eastern Cooperative Oncology Group (ecog) performance status of 1 or greater (n = 139), elevated lactate dehydrogenase (ldh) (n = 105), or prior pelvic radiation (n = 54). Based on phase i results, patients with prior pelvic radiation received capecitabine 750 mg/m2 twice daily. The goal was to ascertain efficacy in a design that was unlikely to cause high levels of toxicity. RESULTS: Median age in the patient cohort was 72 years. A median of 5 and a mean of 8 capecitabine cycles were given (range: 0-50 cycles). Grade 3 or 4 toxicity occurred in 25% of patients during the first 3 cycles (8.1% hand-foot syndrome, 7.7% diarrhea). The response rate was 13.6%, with a 69.7% disease control rate. Median progression-free survival (pfs) was 5.6 months. Post progression, 56 patients received further capecitabine monotherapy (median of 4 additional cycles). Median overall survival duration for the patients was 14.3 months. Median survival was significantly higher for those who, at baseline, had an ecog performance status of 0 (compared with 1 or more) and normal ldh (compared with elevated ldh). CONCLUSIONS: Toxicity is less with dose-reduced capecitabine than with historical full-dose capecitabine, with only a small trade-off in efficacy, seen as a lower objective response rate. The improved tolerability could lead to an increased number of cycles of therapy, and pfs appears to be consistently higher at the lower dose. Those observations should, in the absence of a head-to-head clinical trial, be viewed as compelling evidence that 1000 mg/m2, or even 750 mg/m2, twice daily is an appropriate dose in elderly or frail patients with acrc.
RESUMO
AIMS: A few case series in adults have described the characteristics of epithelioid glioblastoma (e-GB), one of the rarest variants of this cancer. We evaluated clinical, radiological, histological and molecular characteristics in the largest series to date of paediatric e-GB. METHODS: Review of clinical characteristics and therapy, imaging studies and histology was performed in patients younger than 22 years with e-GB seen at our institution over 15 years. Sequencing of hotspot mutations and fluorescence in situ hybridization of relevant genes were undertaken. RESULTS: Median age at diagnosis of six patients was 7.6 years. Tumours originated in the cerebral cortex (n = 2) or diencephalon (n = 4). Three patients presented with acute, massive haemorrhage and three had leptomeningeal dissemination at diagnosis. Paediatric e-GB had the typical histological characteristics seen in adult tumours. Universal immunoreactivity for INI1 and lack of diverse protein expression were seen in all cases. One tumour had a chromosome 22q loss. Three tumours (50%) harboured a BRAF: p.V600E. One thalamic tumour had an H3F3A p.K27M. All patients received radiation therapy with (n = 3) or without chemotherapy (n = 3). All patients experienced tumour progression with a median survival of 169 days. One patient with nonmetastatic disease had early leptomeningeal progression. Two patients had symptomatic tumour spread outside the central nervous system (CNS) through a ventriculoperitoneal shunt. One additional patient had widespread metastases outside the CNS identified at autopsy. CONCLUSIONS: Paediatric e-GBs are rare cancers with an aggressive behaviour that share histological and genetic characteristics with their adult counterparts. BRAF inhibition is a potential treatment for these tumours.
Assuntos
Neoplasias Encefálicas/diagnóstico , Glioblastoma/diagnóstico , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Criança , Pré-Escolar , Feminino , Glioblastoma/diagnóstico por imagem , Glioblastoma/genética , Glioblastoma/patologia , Humanos , Masculino , RadiografiaRESUMO
BACKGROUND AND PURPOSE: Posterior fossa type A (PFA) ependymomas have 2 molecular subgroups (PFA-1 and PFA-2) and 9 subtypes. Gene expression profiling suggests that PFA-1 and PFA-2 tumors have distinct developmental origins at different rostrocaudal levels of the brainstem. We, therefore, tested the hypothesis that PFA-1 and PFA-2 ependymomas have different anatomic MR imaging characteristics at presentation. MATERIALS AND METHODS: Two neuroradiologists reviewed the preoperative MR imaging examinations of 122 patients with PFA ependymomas and identified several anatomic characteristics, including extension through the fourth ventricular foramina and encasement of major arteries and tumor type (midfloor, roof, or lateral). Deoxyribonucleic acid methylation profiling assigned ependymomas to PFA-1 or PFA-2. Information on PFA subtype from an earlier study was also available for a subset of tumors. Associations between imaging variables and subgroup or subtype were evaluated. RESULTS: No anatomic imaging variable was significantly associated with the PFA subgroup, but 5 PFA-2c subtype ependymomas in the cohort had a more circumscribed appearance and showed less tendency to extend through the fourth ventricular foramina or encase blood vessels, compared with other PFA subtypes. CONCLUSIONS: PFA-1 and PFA-2 ependymomas did not have different anatomic MR imaging characteristics, and these results do not support the hypothesis that they have distinct anatomic origins. PFA-2c ependymomas appear to have a more anatomically circumscribed MR imaging appearance than the other PFA subtypes; however, this needs to be confirmed in a larger study.
Assuntos
Ependimoma , Neoplasias Infratentoriais , Estudos de Coortes , Ependimoma/diagnóstico por imagem , Ependimoma/genética , Ependimoma/patologia , Humanos , Neoplasias Infratentoriais/diagnóstico por imagem , Imageamento por Ressonância Magnética , NeuroimagemRESUMO
To determine whether recognized experts in the area of Hodgkin's disease would agree on the determination of stage when various types of extranodal disease are present, we asked senior investigators at 15 major centers to assign a stage to four different patients. In general, these experts agreed in cases representing the extremes of difference between localized and distant extranodal disease. However, when presented with patients with nearby but not contiguous extranodal disease of lung or bone, one half of the experts classified this as an E lesion and one half as stage IV. This disagreement in stage assignment has implications not only for individual patient treatment, but also for reporting of clinical trials. Over-assignment of stage IV has the practical result of "improving" the results of treatment of both low stage (by removing higher risk patients) and advanced stage patients (by including better risk patients). Papers reporting the results of treatment of Hodgkin's disease should include information concerning how patients with extranodal disease were separated into those with E lesions and those with stage IV disease.
Assuntos
Doença de Hodgkin/patologia , Doença de Hodgkin/classificação , Doença de Hodgkin/diagnóstico , HumanosRESUMO
Seventy patients with advanced Hodgkin's disease, 54 with new disease, and 16 in first relapse after initial radiotherapy, have been treated with a seven-drug, 8-month program: MOPP (nitrogen mustard, vincristine, procarbazine, prednisone)/ABV (Adriamycin [Adria Laboratories of Canada, Mississauga, Ontario], bleomycin, vinblastine) hybrid. A single involved field of radiotherapy was given to selected partial responders after 6 months of chemotherapy. Forty-six of the 52 (88%) evaluable new-disease patients and 14 of the 16 (87%) evaluable patients with relapsing disease reached a complete response. The actuarial overall survival at 49 months for the patients with new disease was 90% (median follow-up from diagnosis was 27 months). For the patients with relapsing disease, the actuarial survival at 54 months was 79% (median follow-up from diagnosis was 27 months). The actuarial relapse-free survival at 41 months for complete responders was 93% for patients with new disease (median follow-up after treatment was 20 months) and 80% for those with relapsing disease (median follow-up after treatment was 27 months). Toxicity was moderate, with two treatment-related deaths and eight episodes of serious infection. These results compare favorably with the best results reported in the literature. Furthermore, they were achieved with a moderate level of toxicity, high drug delivery rates, and a relatively short duration of treatment. The efficacy and toxicity data of the MOPP/ABV hybrid program will now be evaluated in a prospectively randomized multicenter study.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Análise Atuarial , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bleomicina/administração & dosagem , Bleomicina/efeitos adversos , Medula Óssea/efeitos dos fármacos , Terapia Combinada , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Seguimentos , Doença de Hodgkin/mortalidade , Doença de Hodgkin/radioterapia , Humanos , Mecloretamina/administração & dosagem , Mecloretamina/efeitos adversos , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Pneumonia por Pneumocystis/induzido quimicamente , Prednisona/administração & dosagem , Prednisona/efeitos adversos , Procarbazina/administração & dosagem , Procarbazina/efeitos adversos , Embolia Pulmonar/induzido quimicamente , Vimblastina/administração & dosagem , Vimblastina/efeitos adversos , Vincristina/administração & dosagem , Vincristina/efeitos adversos , Vômito/induzido quimicamenteRESUMO
Elderly patients with advanced-stage diffuse large-cell lymphomas (DLCLs) are either excluded from or under-represented in most clinical trials of combination chemotherapy regimens because they tolerate treatment poorly and usually have a worse outcome. We report two brief weekly chemotherapy regimens designed specifically for elderly patients. Eligible patients were aged 65 to 85 years, had advanced-stage DLCL (diffuse mixed, diffuse large-cleaved or noncleaved, immunoblastic, or diffuse large-cell not otherwise specified). Advanced stage was defined as Ann Arbor stage III or IV or stage I or II with a mass greater than 10 cm or B symptoms. Low-dose doxorubicin, cyclophosphamide, vincristine, bleomycin, and prednisone (LD-ACOP-B) accrued 40 patients between March 1983 and September 1985; 65% achieved a complete response (CR), there were two toxic deaths, the actuarial failure-free survival (FFS) is 19%, disease-specific survival (DSS) 30%, and overall survival (OS) 28%, with a maximum follow-up of 6 years. The regimen of etoposide, doxorubicin, vincristine, bleomycin, and prednisone (VABE) accrued 32 patients between July 1985 and June 1987; 63% achieved a CR, there were two toxic deaths, and the actuarial FFS is 34%, DSS 45%, and OS 36%, with a maximum follow-up of 4 years. There is no difference in FFS, DSS, or OS between these two regimens. VABE caused more myelosuppression and infectious complications, although the toxic death rates were similar. We prefer LD-ACOP-B because follow-up is longer and toxicity is less.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Idoso , Bleomicina/administração & dosagem , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Esquema de Medicação , Etoposídeo/administração & dosagem , Feminino , Humanos , Linfoma Difuso de Grandes Células B/mortalidade , Linfoma Difuso de Grandes Células B/patologia , Masculino , Estadiamento de Neoplasias , Prednisona/administração & dosagem , Análise de Sobrevida , Vincristina/administração & dosagemRESUMO
We investigated the impact of early brief chemotherapy on the natural history of primary testicular lymphoma. We compared the outcome for patients seen before 1980--a group primarily managed with orchiectomy and regional radiation--with those seen from 1980 to 1986--a prospectively and consecutively gathered group who were offered brief chemotherapy in addition to standard orchiectomy and irradiation. The historical and study groups were similar in clinical characteristics. However, the chemotherapy group had a better relapse-free survival, 93% v 50% (P less than .02), and overall survival, 93% v 50% (P less than .02). With a median follow-up of 44 months in the chemotherapy group, it is clear that the use of early, brief chemotherapy strongly alters the natural history of testicular lymphoma by preventing relapses, the large majority of which occur early after regional therapy. We conclude that a program incorporating orchiectomy, early brief chemotherapy, and involved-field radiation therapy confers the following benefits on patients with primary testicular lymphoma: (1) laparotomy is not needed for staging; (2) relapses, including those in the opposite testicle and CNS, are largely prevented; and (3) toxicity can be kept to a modest level acceptable in elderly patients.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma/tratamento farmacológico , Neoplasias Testiculares/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Terapia Combinada , Seguimentos , Humanos , Linfoma/mortalidade , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Orquiectomia , Neoplasias Testiculares/mortalidadeRESUMO
One hundred twenty-six patients with diffuse large-cell lymphoma were treated with methotrexate with leucovorin, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin (MACOP-B) between April 1981 and June 1986. Univariate and multivariate analyses were performed using overall survival as of September 1989 as the end point. Four independent negative predictors of survival were identified: presence of B symptoms; more than two involved lymph node sites; more than one extranodal site (variables related to tumor burden), and age older than 60, a variable related to the patient's ability to tolerate treatment. Each variable contributed the same relative risk of dying and, accordingly, this simple predictive formula was developed empirically: (4-N) x 30 = the approximate percentage of chance of survival at 5 years. "N" is the number of predictive variables present. The same four predictors were also found to be significant by multivariate analysis when only those patients achieving a complete response were analyzed.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Adolescente , Adulto , Idoso , Bleomicina/administração & dosagem , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Feminino , Humanos , L-Lactato Desidrogenase/metabolismo , Leucovorina/administração & dosagem , Metástase Linfática , Linfoma Difuso de Grandes Células B/metabolismo , Linfoma Difuso de Grandes Células B/mortalidade , Linfoma Difuso de Grandes Células B/patologia , Masculino , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Prednisona/administração & dosagem , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Vincristina/administração & dosagemRESUMO
PURPOSE: To examine the clinical course of patients who experienced a late relapse after initial curative chemotherapy for advanced-stage diffuse large-cell lymphoma. PATIENTS AND METHODS: Between April 1981 and June 1986, 127 patients with de novo advanced-stage diffuse large-cell lymphoma were treated with a 12-week chemotherapy program (methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin [MACOP-B]). The overall survival rate at 10 years is 52%. One hundred six patients (83%) entered a complete remission (CR) and 43 of them relapsed. With a median follow-up duration of 146 months, 26 patients relapsed early and 17 relapsed late, ie, after a continuous CR (cCR) of greater than 24 months. All late relapses occurred in patients with B-cell lymphoma. RESULTS: After 24 months from diagnosis, the rate of late relapse averaged 2.2% per year and reached a projected 22% actuarial risk of late relapse after 10 years. The median time to late relapse was 69 months (range, 38 to 141). Ten patients relapsed with aggressive histologic subtypes and were treated with curative intent using anthracycline-based chemotherapy. Four remain in second CR, one is alive with disease, and five died of disease or while on treatment. The 6-year overall survival rate from the time of relapse (SFR) for these 10 patients is 42%. Six patients relapsed with low-grade follicular lymphoma. These patients received various treatments intended to control, but not necessarily cure disease. One is in second CR, one is alive with disease, and four died of disease or while on treatment. The 6-year overall SFR rate for these six patients is 40%. bcl-2 translocation and Bcl-2 protein expression at diagnosis did not predict for the type of late relapse. One patient did not undergo repeat biopsy at relapse and died 9 months later despite aggressive therapy. CONCLUSION: Curative therapy should be attempted in patients who relapse late with aggressive-histology lymphoma and those who relapse with follicular histology may benefit from palliative treatment. The behavior of late-relapse lymphoma is similar to de novo lymphoma, with outcome dictated by the histologic subtype at relapse.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Terapia de Salvação , Adulto , Biomarcadores Tumorais/metabolismo , Bleomicina/administração & dosagem , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Esquema de Medicação , Feminino , Humanos , Leucovorina/administração & dosagem , Linfoma Difuso de Grandes Células B/metabolismo , Linfoma Difuso de Grandes Células B/mortalidade , Linfoma Difuso de Grandes Células B/patologia , Linfoma não Hodgkin/tratamento farmacológico , Masculino , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prednisona/administração & dosagem , Prognóstico , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Recidiva , Taxa de Sobrevida , Fatores de Tempo , Vincristina/administração & dosagemRESUMO
PURPOSE: The results of a prospective, phase II trial of an 8-week treatment program consisting of epirubicin or doxorubicin, vincristine, cyclophosphamide, etoposide, and prednisone (P/DOCE) for elderly patients with advanced large-cell lymphoma are reported and compared with previous phase II studies conducted in similar patients at the same institution. PATIENTS AND METHODS: Between March 1988 and September 1991, 63 previously untreated patients aged 65 to 85 years (median, 75) with advanced-stage diffuse large-cell lymphoma, defined as Ann Arbor stage III or IV or stage I or II with B symptoms or bulky disease, were enrolled on a brief, 8-week protocol consisting of five outpatient chemotherapy treatments. RESULTS: The complete response (CR) rate was 62%. The treatment-related mortality rate was 8%, the actuarial 4-year failure-free survival (FFS) rate was 41%, and the overall survival (OS) rate was 45%. These results were compared with two earlier, 12-week protocols, low-dose doxorubicin, cyclophosphamide, vincristine, bleomycin, and prednisone (LD-ACOB-B) and etoposide, doxorubicin, bleomycin, and prednisone (VABE), performed at the same center. There was no difference in outcome among the three regimens. If all 133 patients treated on any one of these three specially designed regimen for elderly patients are combined, the projected 5-year OS rate is 38%. CONCLUSION: The 8-week P/DOCE chemotherapy regimen is equal in efficacy and similar in toxicity to 3 months of chemotherapy administered on a weekly schedule and similar to the results reported in the literature for longer, anthracycline-based chemotherapy treatments. There does not appear to be any improvement in outcome from more protracted treatment programs compared with the 8-week P/DOCE protocol.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Epirubicina/administração & dosagem , Etoposídeo/administração & dosagem , Feminino , Humanos , Linfoma Difuso de Grandes Células B/patologia , Masculino , Prednisona/administração & dosagem , Probabilidade , Prognóstico , Estudos Prospectivos , Resultado do Tratamento , Vincristina/administração & dosagemRESUMO
PURPOSE: This randomized, prospective trial compares outcomes for patients with advanced Hodgkin's disease treated with mechlorethamine, vincristine, procarbazine, and prednisone (MOPP)/doxorubicin, bleomycin, and vinblastine (ABV) hybrid regimen or alternating MOPP/doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD). METHODS: Three hundred one patients with advanced Hodgkin's disease were randomized to receive MOPP/ ABV hybrid regimen or alternating MOPP/ABVD after stratification for prior treatment, B symptoms, and treatment center. Eligible patients were either previously untreated and found to have stage IIIB, IVA, or IVB disease or previously treated with wide-field irradiation. Responding patients received a minimum of eight cycles of chemotherapy. Those with residual disease in a localized region received irradiation between the sixth and seventh cycle of treatment. RESULTS: Response rates to the two regimens were similar. Five-year overall survival rates were 81% and 83% for MOPP/ABV hybrid and alternating MOPP/ ABVD, respectively (P = .74; 95% confidence interval [CI] for the difference, -11% to 7%). Five-year failure-free survivals were 71% and 67% for MOPP/ABV hybrid and alternating MOPP/ABVD, respectively (P = .87; 95% CI for the difference, -9% to 17%). Significantly more episodes of febrile neutropenia and stomatitis were observed with the MOPP/ABV hybrid regimen; there was no significant difference in fatal toxicity. Patients with predefined, high-quality partial responses (PR-1s) had results similar to those with complete responses (CRs). Planned subset analysis showed no significant difference in outcome between the two arms of the trial for patients with newly diagnosed disease (5-year failure-free survival rates were 70% for MOPP/ABV hybrid and 59% for alternating MOPP/ABVD; P = .180), but superiority of alternating MOPP/ABVD for patients with prior irradiation (5-year failure-free survival 94% v 73%; P = .017). CONCLUSION: MOPP/ABV hybrid and alternating MOPP/ABVD regimens are equally effective for patients with advanced Hodgkin's disease.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Análise Atuarial , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bleomicina/administração & dosagem , Canadá , Dacarbazina/administração & dosagem , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Esquema de Medicação , Feminino , Doença de Hodgkin/patologia , Humanos , Masculino , Mecloretamina/administração & dosagem , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prednisona/administração & dosagem , Procarbazina/administração & dosagem , Análise de Sobrevida , Resultado do Tratamento , Vimblastina/administração & dosagem , Vincristina/administração & dosagemRESUMO
Between February 1980 and July 1984, 79 patients with newly diagnosed advanced Hodgkin's disease were treated with a new seven-drug regimen, the mechlorethamine, vincristine, procarbazine, prednisone, doxorubicin, bleomycin, vinblastine) MOPP/ABV) Hybrid. The treatment plan allowed for a course of involved-field radiotherapy (RT) (3,500 cGy in 20 fractions) to a single area of residual lymph-node-related abnormalities if still present after six cycles of chemotherapy. Of 76 evaluable patients, 74 (97.5%) achieved complete remission (CR), ten (13%) with assistance of involved-field RT. Only two patients (2.5%) were primary treatment failures. Seven patients (9.5%) relapsed; all relapses occurred in the first 24 months of follow-up. The majority of relapses were males with large mediastinal masses and B symptoms. The actuarial overall survival of all 79 patients with the maximum and median follow-up times of 80 and 53 months, respectively, is 93.5%. The actuarial relapse-free survival for the 74 CRs with the maximum and median follow-up times of 71 and 46 months, respectively, is 90.5%. The treatment tolerance was acceptable; only one patient died from causes directly related to the treatment, and less than 10% of patients required hospitalization for suspected or proven systemic infection. The treatment delivery was excellent, as greater than 75% of the treated patients took greater than 90% of the prescribed treatment; greater than 90% of patients received at least 75% of the calculated doses of drugs. This long-term follow-up report supports our initial impression that the MOPP/ABV Hybrid chemotherapy is an effective and well-tolerated program for patients with advanced Hodgkin's disease.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bleomicina/administração & dosagem , Bleomicina/efeitos adversos , Terapia Combinada , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Avaliação de Medicamentos , Feminino , Seguimentos , Doença de Hodgkin/radioterapia , Humanos , Masculino , Mecloretamina/administração & dosagem , Mecloretamina/efeitos adversos , Prednisona/administração & dosagem , Prednisona/efeitos adversos , Procarbazina/administração & dosagem , Procarbazina/efeitos adversos , Vimblastina/administração & dosagem , Vimblastina/efeitos adversos , Vincristina/administração & dosagem , Vincristina/efeitos adversosRESUMO
Between 1981 and 1986, we treated 179 newly diagnosed patients with advanced-stage malignant lymphoma or related conditions with methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone, bleomycin (MACOP-B). Experience with 12 different histologic subtypes indicates that MACOP-B is acceptably tolerated and effective for diffuse large cleaved cell, diffuse large noncleaved cell, diffuse mixed large and small cleaved cell, immunoblastic, and discordant lymphomas but not for angioimmunoblastic lymphadenopathy or for diffuse small cleaved cell, follicular large cell, follicular mixed large and small cleaved cell, acquired immune deficiency syndrome (AIDS)-related, unclassifiable, or small noncleaved cell lymphomas. Pooled long-term results for the 126 patients with variants of diffuse large cell lymphoma (cleaved, noncleaved, immunoblastic, and mixed) show an actuarial relapse-free survival of 67% for the 86% of patients who had a complete response and an overall survival for all patients of 65% at 78 months of follow-up. Analysis of toxicity reveals a substantially higher risk of lethal toxicity in patients over 59 years of age. MACOP-B should only be used for patients with one of the diagnoses for which it is effective; meticulous care should be taken to prevent severe toxicity in older patients.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma não Hodgkin/tratamento farmacológico , Síndrome da Imunodeficiência Adquirida/complicações , Adulto , Fatores Etários , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bleomicina/administração & dosagem , Bleomicina/efeitos adversos , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Avaliação de Medicamentos , Humanos , Leucovorina/administração & dosagem , Leucovorina/efeitos adversos , Linfoma não Hodgkin/classificação , Linfoma não Hodgkin/etiologia , Metotrexato/administração & dosagem , Metotrexato/efeitos adversos , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Prednisona/efeitos adversos , Vincristina/administração & dosagem , Vincristina/efeitos adversosRESUMO
This paper summarizes our experience with MACOP-B chemotherapy (methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone, bleomycin) in 125 patients with advanced stage, diffuse, large cell non-Hodgkin's lymphoma referred to the Cancer Control Agency of British Columbia between April 1981 and June 1986. Complete response (CR) was achieved in 105 patients (84%), partial response (PR) in 18 patients (14.4%) and primary treatment failure occurred in two patients (1.6%). Fifteen of the PRs and both nonresponders succumbed to their disease. Of the 105 CRs, 23 patients (21%) suffered a relapse; 14 of the relapsers eventually died from their lymphoma, five are in second CR, three are receiving further therapy, and one has histologic evidence of asymptomatic, low-grade lymphoma. Three deaths were unrelated to lymphoma. Overall toxicity was acceptable, with only six treatment-related deaths (4.8%). The incidence of nonfatal systemic proven or suspected infections was 10%. Mucocutaneous side effects remain the most frequent toxicity of the MACOP-B protocol. More than half of the 125 patients received at least a portion of MACOP-B from community oncologists. The results of treatment with MACOP-B remain at least comparable to the best reported in the literature, yet they have been achieved with less toxicity, over shorter periods of time, and with diminished socioeconomic impact on patients. However, improvement on these results is necessary both in terms of efficacy and toxicity. A new variant of MACOP-B is now being tested and our preliminary experience has been encouraging.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma não Hodgkin/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bleomicina/administração & dosagem , Bleomicina/efeitos adversos , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Feminino , Humanos , Leucovorina/administração & dosagem , Leucovorina/efeitos adversos , Masculino , Metotrexato/administração & dosagem , Metotrexato/efeitos adversos , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Prednisona/efeitos adversos , Fatores de Tempo , Vincristina/administração & dosagem , Vincristina/efeitos adversosRESUMO
Seventy-six patients with previously untreated advanced Hodgkin's disease have been treated with the MOPP/ABV (mechlorethamine, vincristine, procarbazine, prednisone/doxorubicin, bleomycin, vincristine) hybrid program. Ten patients also received involved field radiation to the mediastinum for residual nodal disease after six cycles of chemotherapy. Of the 74 evaluable patients, 71 (96%) had a complete response. The actuarial relapse-free survival for the complete responders after 62 months off treatment is 90% (median follow-up from treatment completion was 35 months; range, 4 to 62 months). Actuarial overall survival for all 76 patients including all causes of death is 95% (median follow-up time from diagnosis was 43 months; range, 4 to 70 months). Toxicity was modest. Only one death occurred during treatment, and toxicity-related hospitalization was necessary for only 8% of patients. Failure analysis indicates that a disproportionate number of treatment failures occurred in the sub-group with B symptoms and a mediastinal mass ratio greater than one third the transthoracic diameter. This updated report confirms the efficacy and safety of the MOPP/ABV hybrid program for advanced Hodgkin's disease, which is now being tested in a prospective, randomized, multicenter trial.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bleomicina/efeitos adversos , Bleomicina/uso terapêutico , Doxorrubicina/efeitos adversos , Doxorrubicina/uso terapêutico , Esquema de Medicação , Feminino , Humanos , Masculino , Mecloretamina/efeitos adversos , Mecloretamina/uso terapêutico , Pessoa de Meia-Idade , Prednisona/efeitos adversos , Prednisona/uso terapêutico , Procarbazina/efeitos adversos , Procarbazina/uso terapêutico , Vimblastina/efeitos adversos , Vimblastina/uso terapêutico , Vincristina/efeitos adversos , Vincristina/uso terapêuticoRESUMO
Single-agent gemcitabine, when given in doses of > or = 1,250 mg/m2 weekly x 3 with a 1-week break, induces responses in approximately 20% of untreated patients with non-small cell lung cancer. This phase II study was undertaken to determine the efficacy of weekly administration of gemcitabine 1,500 mg/m2 combined with cisplatin 30 mg/m2 x 3 with a rest period of 1 week. Patients younger than 75 years were eligible if they had stage III/IV non-small cell lung cancer, a life expectancy > or = 12 weeks, hemoglobin > or = 10 g/dL, absolute granulocyte count > or = 10(9)/L, platelets > or = 100 x 10(9)/L, hepatic enzymes no more than three times the upper limit of normal, and serum creatinine < or = 130 micromol/L. There were 22 men and 18 women, with a median age of 60 years; 35 had a performance status of 0 or 1. Pathology included adenocarcinoma in 22 patients, squamous cell carcinoma in nine, large cell carcinoma in seven, and mixed non-small cell lung cancer in two. Six patients had stage III and 34 had stage IV tumors. Of the 39 patients eligible for response evaluation, partial remission was seen in 10, for an overall response rate of 26% (95% confidence interval, 12% to 41%). The median duration of response was 19 weeks (range, 7 to 32+ weeks). Grade 3/4 anemia was seen in 11 patients, and 21 patients required red blood cell transfusions. Grade 3/4 neutropenia occurred in 22 patients and grade 3/4 thrombocytopenia in 21 patients. One patient experienced febrile neutropenia Hematologic toxicity, particularly thrombocytopenia, was cumulative over time. Nonhematologic toxicity was modest, but one patient stopped therapy because of a grade 2 skin rash and one stopped because of a grade 4 pulmonary toxicity, both of which were thought to be related to gemcitabine. The modest activity of weekly gemcitabine and weekly cisplatin seen in this trial does not suggest in vivo synergy for these two agents as administered using this schedule and these doses.
Assuntos
Antimetabólitos Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Cisplatino/administração & dosagem , Desoxicitidina/análogos & derivados , Neoplasias Pulmonares/tratamento farmacológico , Ribonucleotídeo Redutases/antagonistas & inibidores , Adulto , Idoso , Idoso de 80 Anos ou mais , Anemia/induzido quimicamente , Antimetabólitos Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cisplatino/efeitos adversos , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Esquema de Medicação , Toxidermias/etiologia , Feminino , Humanos , Pulmão/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Trombocitopenia/induzido quimicamente , Resultado do Tratamento , GencitabinaRESUMO
A case of kappa light-chain myeloma with pleural involvement is reported. The diagnosis was made by pleural biopsy, pleural fluid cytology, and urine immunoelectrophoresis. A review of the literature on pleural involvement in multiple myeloma revealed that this is the first reported case in patients with light-chain myeloma.
Assuntos
Cadeias Leves de Imunoglobulina/urina , Cadeias kappa de Imunoglobulina/urina , Mieloma Múltiplo/complicações , Derrame Pleural/complicações , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/imunologia , Mieloma Múltiplo/patologia , Mieloma Múltiplo/terapia , Derrame Pleural/diagnóstico por imagem , RadiografiaRESUMO
A 62-year-old woman had multiple plasmacytomas of the skin with no roentgenographic or bone marrow evidence of multiple myeloma. Serum IgA-lambda level was increased to 1,000 mg/dL (normal range, 90 to 450 mg/dL). The skin lesions regressed completely when the patient was treated with melphalan. She had recurrence of a skin plasmacytoma and lytic bone lesions ten months later and died of bronchopneumonia 11 months after the was first seen. Solitary skin plasmacytomas are rare, and multiple skin plasmacytomas are even rarer. Occasionally, these lesions may precede roentgenographic and bone marrow evidence of multiple myeloma.
Assuntos
Mieloma Múltiplo/patologia , Neoplasias Cutâneas/patologia , Feminino , Humanos , Imunoglobulina A/análise , Cadeias lambda de Imunoglobulina/análise , Melfalan/uso terapêutico , Pessoa de Meia-Idade , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/imunologia , Recidiva Local de Neoplasia , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/imunologiaRESUMO
We evaluated the efficacy and toxicity of ketoconazole versus nystatin antimycotic prophylaxis in a prospective randomized study of 32 patients receiving intensive weekly outpatient combination chemotherapy for non-Hodgkin's lymphoma with crossover to the other drug if failure occurred. Thirteen patients were assigned to nystatin and 19 to ketoconazole. Fungal infections occurred in three patients receiving nystatin (16%) and one patient receiving ketoconazole (8%); one patient refused his assigned drug due to taste intolerance. Including the crossover courses of drug, the failure rate associated with ketoconazole was 6% while that for nystatin was 20% (p = 0.23). We favor ketoconazole as antifungal prophylaxis during antilymphoma chemotherapy because of at least equivalent and possibly superior efficacy, better acceptance by patients, easier administration, and systemic absorption.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Cetoconazol/uso terapêutico , Linfoma não Hodgkin/complicações , Micoses/prevenção & controle , Nistatina/uso terapêutico , Idoso , Bleomicina/uso terapêutico , Ensaios Clínicos como Assunto , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Feminino , Humanos , Cetoconazol/administração & dosagem , Cetoconazol/efeitos adversos , Leucovorina/uso terapêutico , Linfoma não Hodgkin/tratamento farmacológico , Masculino , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Nistatina/administração & dosagem , Nistatina/efeitos adversos , Prednisona/uso terapêutico , Estudos Prospectivos , Distribuição Aleatória , Fatores de Tempo , Vincristina/uso terapêuticoRESUMO
BACKGROUND AND PURPOSE: High-field-strength intraoperative MR imaging has emerged as a powerful adjunct for resection of brain tumors. However, its exact role has not been firmly established. We sought to determine the impact of 3T-intraoperative MRI on the surgical management of childhood CNS tumors. MATERIALS AND METHODS: We evaluated patient data from a single academic children's hospital during a consecutive 24-month period after installation of a 3T-intraoperative MRI. Tumor location, histology, surgical approach, operating room time, presence and volume of residual tumor, need for tumor and non-tumor-related reoperation, and anesthesia- and MR imaging-related complications were evaluated. Comparison with pre-intraoperative MRI controls was performed. RESULTS: One hundred ninety-four patients underwent intraoperative MRI-guided surgery. Of these, 168 were 18 years or younger (mean, 8.9 ± 5.0 years; 108 males/60 females). There were 65 posterior fossa tumors. The most common tumors were pilocytic astrocytoma (n = 31, 19%), low-grade glioma (n = 31, 19%), and medulloblastoma (n = 20, 12%). An average of 1.2 scanning sessions was performed per patient (maximum, 3). There were no MR imaging-related safety issues. Additional tumor was resected after scanning in 21% of patients. Among patients with a preoperative goal of gross total resection, 93% achieved this goal. The 30-day reoperation rate was <1% (n = 1), and no patient required additional postoperative MR imaging during the same hospital stay. CONCLUSIONS: Intraoperative MRI is safe and increases the likelihood of gross total resection, albeit with increased operating room time, and reduces the need for early reoperation or repeat sedation for postoperative scans in children with brain tumors.