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1.
Neuro Oncol ; 26(2): 335-347, 2024 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-37758193

RESUMO

BACKGROUND: Central nervous system (CNS) WHO grade 2 low-grade glioma (LGG) patients are at high risk for recurrence and with unfavorable long-term prognosis due to the treatment resistance and malignant transformation to high-grade glioma. Considering the relatively intact systemic immunity and slow-growing nature, immunotherapy may offer an effective treatment option for LGG patients. METHODS: We conducted a prospective, randomized pilot study to evaluate the safety and immunological response of the multipeptide IMA950 vaccine with agonistic anti-CD27 antibody, varlilumab, in CNS WHO grade 2 LGG patients. Patients were randomized to receive combination therapy with IMA950 + poly-ICLC and varlilumab (Arm 1) or IMA950 + poly-ICLC (Arm 2) before surgery, followed by adjuvant vaccines. RESULTS: A total of 14 eligible patients were enrolled in the study. Four patients received pre-surgery vaccines but were excluded from postsurgery vaccines due to the high-grade diagnosis of the resected tumor. No regimen-limiting toxicity was observed. All patients demonstrated a significant increase of anti-IMA950 CD8+ T-cell response postvaccine in the peripheral blood, but no IMA950-reactive CD8+ T cells were detected in the resected tumor. Mass cytometry analyses revealed that adding varlilumab promoted T helper type 1 effector memory CD4+ and effector memory CD8+ T-cell differentiation in the PBMC but not in the tumor microenvironment. CONCLUSION: The combinational immunotherapy, including varlilumab, was well-tolerated and induced vaccine-reactive T-cell expansion in the peripheral blood but without a detectable response in the tumor. Further developments of strategies to overcome the blood-tumor barrier are warranted to improve the efficacy of immunotherapy for LGG patients.


Assuntos
Anticorpos Monoclonais Humanizados , Vacinas Anticâncer , Glioma , Peptídeos , Humanos , Projetos Piloto , Leucócitos Mononucleares , Estudos Prospectivos , Glioma/tratamento farmacológico , Diferenciação Celular , Microambiente Tumoral
2.
J Clin Invest ; 132(3)2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-34882581

RESUMO

BACKGROUNDLong-term prognosis of WHO grade II low-grade gliomas (LGGs) is poor, with a high risk of recurrence and malignant transformation into high-grade gliomas. Given the relatively intact immune system of patients with LGGs and the slow tumor growth rate, vaccines are an attractive treatment strategy.METHODSWe conducted a pilot study to evaluate the safety and immunological effects of vaccination with GBM6-AD, lysate of an allogeneic glioblastoma stem cell line, with poly-ICLC in patients with LGGs. Patients were randomized to receive the vaccines before surgery (arm 1) or not (arm 2) and all patients received adjuvant vaccines. Coprimary outcomes were to evaluate safety and immune response in the tumor.RESULTSA total of 17 eligible patients were enrolled - 9 in arm 1 and 8 in arm 2. This regimen was well tolerated with no regimen-limiting toxicity. Neoadjuvant vaccination induced upregulation of type-1 cytokines and chemokines and increased activated CD8+ T cells in peripheral blood. Single-cell RNA/T cell receptor sequencing detected CD8+ T cell clones that expanded with effector phenotype and migrated into the tumor microenvironment (TME) in response to neoadjuvant vaccination. Mass cytometric analyses detected increased tissue resident-like CD8+ T cells with effector memory phenotype in the TME after the neoadjuvant vaccination.CONCLUSIONThe regimen induced effector CD8+ T cell response in peripheral blood and enabled vaccine-reactive CD8+ T cells to migrate into the TME. Further refinements of the regimen may have to be integrated into future strategies.TRIAL REGISTRATIONClinicalTrials.gov NCT02549833.FUNDINGNIH (1R35NS105068, 1R21CA233856), Dabbiere Foundation, Parker Institute for Cancer Immunotherapy, and Daiichi Sankyo Foundation of Life Science.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Vacinas Anticâncer , Carboximetilcelulose Sódica/análogos & derivados , Glioma , Terapia Neoadjuvante , Poli I-C/administração & dosagem , Polilisina/análogos & derivados , Microambiente Tumoral/imunologia , Vacinação , Adulto , Idoso , Vacinas Anticâncer/administração & dosagem , Vacinas Anticâncer/imunologia , Carboximetilcelulose Sódica/administração & dosagem , Feminino , Glioma/imunologia , Glioma/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Polilisina/administração & dosagem
3.
Neurooncol Pract ; 6(3): 218-225, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31386027

RESUMO

BACKGROUND: No studies have examined the fertility priorities of women undergoing treatment for their glioma. Glioma patients frequently undergo chemotherapy as part of their treatment; however, it is unknown whether patients truly are aware of its possible effects on their fertility. Our objective was to assess the fertility priorities of glioma patients and ascertain whether female glioma patients are being effectively counseled on the effects of chemotherapy on their fertility prior to beginning treatment. METHODS: The sample was composed of female patients from the Neuro-oncology clinic of the University of California, San Francisco. Participants completed a cross-sectional survey between October 2010 and December 2013 exploring their attitudes toward fertility and their experience with fertility counseling prior to chemotherapy initiation. RESULTS: Seventy-two women completed the survey. Analysis of the survey results showed that 30% of women receiving chemotherapy reported having a discussion regarding fertility preservation prior to beginning treatment. Of those who reported having this discussion, 80% were aware that chemotherapy could negatively affect their fertility. Many women reported that while fertility preservation was not important to them at the time of diagnosis, it was a priority for them at the time of survey completion. Although interest in having children tended to decrease after cancer treatment, the majority of respondents reported wanting a child after treatment. CONCLUSIONS: The data obtained in this study suggest a lack of understanding of reproductive priorities, which may be addressed with a more comprehensive fertility discussion prior to beginning treatment.

4.
Cancer Chemother Pharmacol ; 79(3): 603-610, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28233053

RESUMO

PURPOSE: Preclinical activity of irinotecan has been seen in glioma models, but only modest efficacy has been noted in clinical studies, perhaps related to drug distribution and/or pharmacokinetic limitations. In preclinical testing, irinotecan liposome injection (nal-IRI) results in prolongation of drug exposure and higher tissue levels of drug due to slower metabolism and the effect of enhanced permeability and retention. The objective of the current study was to assess the safety and pharmacokinetics (PK) of nal-IRI and to determine the maximum tolerated dose (MTD) in patients with recurrent high-grade glioma stratified based on UGT1A1 genotyping. METHODS: This phase I study stratified patients with recurrent high-grade glioma into 2 groups by UGT1A1 status: homozygous WT ("WT") vs heterozygous WT/*28 ("HT"). Patients who were homozygous *28 were ineligible. The design was a standard 3 + 3 phase I design. WT patients were started at 120 mg/m2 intravenously every 3 weeks with dose increases in 60 mg/m2 increments. HT patients were started at 60 mg/m2, with dose increases in 30 mg/m2 increments. The assessment period for dose-limiting toxicity was 1 cycle (21 days). RESULTS: In the WT cohort (n = 16), the MTD was 120 mg/m2. In the HT cohort (n = 18), the MTD was 150 mg/m2. Dose-limiting toxicity in both cohorts included diarrhea, some with associated dehydration and/or fatigue. PK results were comparable to those seen in other PK studies of nal-IRI; UGT1A1*28 genotype (WT vs. HT) did not affect PK parameters. CONCLUSIONS: Nal-IRI had no unexpected toxicities when given intravenously. Of note, UGT1A1 genotype did not correlate with toxicity or affect PK profile.


Assuntos
Antineoplásicos Fitogênicos/farmacocinética , Antineoplásicos Fitogênicos/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Camptotecina/análogos & derivados , Glioma/tratamento farmacológico , Adulto , Idoso , Antineoplásicos Fitogênicos/efeitos adversos , Camptotecina/efeitos adversos , Camptotecina/farmacocinética , Camptotecina/uso terapêutico , Estudos de Coortes , Intervalo Livre de Doença , Relação Dose-Resposta a Droga , Feminino , Genótipo , Glucuronosiltransferase/genética , Humanos , Injeções Intravenosas , Irinotecano , Lipossomos , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade
5.
Neuro Oncol ; 16(7): 984-90, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24637230

RESUMO

BACKGROUND: Both the epidermal growth factor receptor and vascular endothelial growth factor pathways are frequently overexpressed in glioblastoma multiforme. This study combined bevacizumab, a vascular endothelial growth factor inhibitor, and erlotinib, an epidermal growth factor receptor inhibitor, with standard radiation and temozolomide (TMZ), with the goal of improving overall survival (OS). METHODS: Treatment consisted of fractionated radiotherapy to 60 Gy, with daily TMZ at 75 mg/m²/d and erlotinib 150-200 mg/d (or 500-600 mg/d for patients on enzyme-inducing antiepileptic drugs). Bevacizumab was given at 10 mg/kg every 2 weeks, starting ≥4 weeks after surgery. After radiotherapy, adjuvant TMZ was given at 200 mg/m²/d × 5d per 28-day cycle, with unchanged erlotinib and bevacizumab doses. Treatment continued until progression or for 12 months. Efficacy was compared against an institutional historical control. A sample of 55 patients was calculated to provide 85% power to detect a hazard ratio of 0.67 for OS. RESULTS: Fifty-nine patients were enrolled for efficacy analysis after a 15-patient safety lead-in. For the efficacy group, median age was 54 years; median KPS was 90. Gross total and subtotal resections were achieved in 33% and 53%, respectively. The most frequent related grade 3/4 adverse effects were lymphopenia, thrombocytopenia, neutropenia, diarrhea, weight loss, and fatigue. One patient died of disseminated aspergillosis. Median OS was 19.8 months (vs 18 mo for HC, P = .33) and median progression-free survival was 13.5 months (vs 8.6 mo for HC, P = .03). CONCLUSIONS: The combination of bevacizumab, erlotinib, TMZ, and radiotherapy appears to be well tolerated and improved progression-free survival but did not reach the primary endpoint of improved OS.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias Encefálicas/terapia , Quimiorradioterapia , Glioblastoma/terapia , Adulto , Idoso , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bevacizumab , Quimiorradioterapia/efeitos adversos , Terapia Combinada/métodos , Dacarbazina/administração & dosagem , Dacarbazina/efeitos adversos , Dacarbazina/análogos & derivados , Intervalo Livre de Doença , Cloridrato de Erlotinib , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Quinazolinas/administração & dosagem , Quinazolinas/efeitos adversos , Temozolomida , Adulto Jovem
6.
J Neurooncol ; 104(3): 737-44, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21311950

RESUMO

The purpose of this study is to identify the needs of brain tumor patients and their caregivers to provide improved health services to these populations. Two different questionnaires were designed for patients and caregivers. Both questionnaires contained questions pertaining to three realms: disease symptoms/treatment, health care provider, daily living/finances. The caregivers' questionnaires contained an additional domain on emotional needs. Each question was evaluated for the degree of importance and satisfaction. Exploratory analyses determined whether baseline characteristics affect responder importance or satisfaction. Also, areas of high agreement/disagreement in satisfaction between the participating patient-caregiver pairs were identified. Questions for which >50% of the patients and caregivers thought were "very important" but >30% were dissatisfied include: understanding the cause of brain tumors, dealing with patients' lower energy, identifying healthful foods and activities for patients, telephone access to health care providers, information on medical insurance coverage, and support from their employer. In the emotional realm, caregivers identified 9 out of 10 items as important but need further improvement. Areas of high disagreement in satisfaction between participating patient-caregiver pairs include: getting help with household chores (P value = 0.006) and finding time for personal needs (P value < 0.001). This study provides insights into areas to improve services for brain tumor patients and their caregivers. The caregivers' highest amount of burden is placed on their emotional needs, emphasizing the importance of providing appropriate medical and psychosocial support for caregivers to cope with emotional difficulties they face during the patients' treatment process.


Assuntos
Neoplasias Encefálicas/psicologia , Cuidadores/psicologia , Necessidades e Demandas de Serviços de Saúde/estatística & dados numéricos , Qualidade de Vida/psicologia , Atividades Cotidianas , Adaptação Psicológica , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/enfermagem , Emoções , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Estatísticas não Paramétricas , Inquéritos e Questionários , Adulto Jovem
7.
Neuro Oncol ; 11(1): 59-68, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18713953

RESUMO

The purpose of this study was to describe the quality of life (QOL) of low-grade glioma (LGG) patients at baseline prior to chemotherapy and through 12 cycles of temozolomide (TMZ) chemotherapy. Patients with histologically confirmed LGG with only prior surgery were given TMZ for 12 cycles. QOL assessments by the Functional Assessment of Cancer Therapy-Brain (FACT-Br) were obtained at baseline prior to chemotherapy and at 2-month intervals while receiving TMZ. Patients with LGG at baseline prior to chemotherapy had higher reported social well-being scores (mean difference = 5.0; p < 0.01) but had lower reported emotional well-being scores (mean difference = 2.2; p < 0.01) compared to a normal population. Compared to patients with left hemisphere tumors, patients with right hemisphere tumors reported higher physical well-being scores (p = 0.01): 44% could not drive, 26% did not feel independent, and 26% were afraid of having a seizure. Difficulty with work was noted in 24%. Mean change scores at each chemotherapy cycle compared to baseline for all QOL subscales showed either no significant change or were significantly positive (p < 0.01). Patients with LGG on TMZ at baseline prior to chemotherapy reported QOL comparable to a normal population with the exception of social and emotional well-being, and those with right hemisphere tumors reported higher physical well-being scores compared to those with left hemisphere tumors. While remaining on therapy, LGG patients were able to maintain their QOL in all realms. LGG patients' QOL may be further improved by addressing their emotional well-being and their loss of independence in terms of driving or working.


Assuntos
Antineoplásicos Alquilantes/uso terapêutico , Astrocitoma/tratamento farmacológico , Neoplasias Encefálicas/tratamento farmacológico , Dacarbazina/análogos & derivados , Oligodendroglioma/tratamento farmacológico , Avaliação de Resultados em Cuidados de Saúde , Qualidade de Vida , Adulto , Idoso , Astrocitoma/patologia , Astrocitoma/psicologia , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/psicologia , Dacarbazina/uso terapêutico , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Oligodendroglioma/patologia , Oligodendroglioma/psicologia , Prognóstico , Estudos Prospectivos , Perfil de Impacto da Doença , Temozolomida , Resultado do Tratamento , Adulto Jovem
8.
J Clin Oncol ; 27(4): 579-84, 2009 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-19075262

RESUMO

PURPOSE: This open-label, prospective, single-arm, phase II study combined erlotinib with radiation therapy (XRT) and temozolomide to treat glioblastoma multiforme (GBM) and gliosarcoma. The objectives were to determine efficacy of this treatment as measured by survival and to explore the relationship between molecular markers and treatment response. PATIENTS AND METHODS: Sixty-five eligible adults with newly diagnosed GBM or gliosarcoma were enrolled. We intended to treat patients not currently treated with enzyme-inducing antiepileptic drugs (EIAEDs) with 100 mg/d of erlotinib during XRT and 150 mg/d after XRT. Patients receiving EIAEDs were to receive 200 mg/d of erlotinib during XRT and 300 mg/d after XRT. After XRT, the erlotinib dose was escalated until patients developed tolerable grade 2 rash or until the maximum allowed dose was reached. All patients received temozolomide during and after XRT. Molecular markers of epidermal growth factor receptor (EGFR), EGFRvIII, phosphatase and tensin homolog (PTEN), and methylation status of the promotor region of the MGMT gene were analyzed from tumor tissue. Survival was compared with outcomes from two historical phase II trials. RESULTS: Median survival was 19.3 months in the current study and 14.1 months in the combined historical control studies, with a hazard ratio for survival (treated/control) of 0.64 (95% CI, 0.45 to 0.91). Treatment was well tolerated. There was a strong positive correlation between MGMT promotor methylation and survival, as well as an association between MGMT promotor-methylated tumors and PTEN positivity shown by immunohistochemistry with improved survival. CONCLUSION: Patients treated with the combination of erlotinib and temozolomide during and following radiotherapy had better survival than historical controls. Additional studies are warranted.


Assuntos
Neoplasias Encefálicas/tratamento farmacológico , Glioblastoma/tratamento farmacológico , Gliossarcoma/tratamento farmacológico , Adulto , Idoso , Antineoplásicos Alquilantes/administração & dosagem , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/radioterapia , Terapia Combinada , Dacarbazina/administração & dosagem , Dacarbazina/análogos & derivados , Cloridrato de Erlotinib , Glioblastoma/mortalidade , Glioblastoma/radioterapia , Gliossarcoma/mortalidade , Gliossarcoma/radioterapia , Humanos , Pessoa de Meia-Idade , Inibidores de Proteínas Quinases/administração & dosagem , Quinazolinas/administração & dosagem , Temozolomida
9.
Neuro Oncol ; 8(1): 67-78, 2006 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-16443950

RESUMO

The purpose of this study was to define the maximum tolerated dose of erlotinib and characterize its pharmaco-kinetics and safety profile, alone and with temozolomide, with and without enzyme-inducing antiepileptic drugs (EIAEDs), in patients with malignant gliomas. Patients with stable or progressive malignant primary glioma received erlotinib alone or combined with temozolomide in this dose-escalation study. In each treatment group, patients were stratified by coadministration of EIAEDs. Erlotinib was started at 100 mg orally once daily as a 28-day treatment cycle, with dose escalation by 50 mg/day up to 500 mg/day. Temozolomide was administered at 150 mg/m2 for five consecutive days every 28 days, with dose escalation up to 200 mg/m2 at the second cycle. Eightythree patients were evaluated. Rash, fatigue, and diarrhea were the most common adverse events and were generally mild to moderate. The recommended phase 2 dose of erlotinib is 200 mg/day for patients with glioblastoma multiforme who are not receiving an EIAED, 450 mg/day for those receiving temozolomide plus erlotinib with an EIAED, and at least 500 mg/day for those receiving erlotinib alone with an EIAED. Of the 57 patients evaluable for response, eight had a partial response (PR). Six of the 57 patients had a progression-free survival of longer than six months, including four patients with a PR. Coadministration of EIAEDs reduced exposure to erlotinib as compared with administration of erlotinib alone (33%-71% reduction). There was a modest pharmacokinetic interaction between erlotinib and temozolomide. The favorable tolerability profile and evidence of antitumor activity indicate that further investigation of erlotinib is warranted.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Encefálicas/tratamento farmacológico , Glioma/tratamento farmacológico , Adulto , Idoso , Anticonvulsivantes/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Dacarbazina/administração & dosagem , Dacarbazina/efeitos adversos , Dacarbazina/análogos & derivados , Relação Dose-Resposta a Droga , Interações Medicamentosas , Cloridrato de Erlotinib , Feminino , Humanos , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Quinazolinas/administração & dosagem , Quinazolinas/efeitos adversos , Quinazolinas/farmacocinética , Temozolomida , Resultado do Tratamento
10.
Int J Radiat Oncol Biol Phys ; 61(5): 1454-9, 2005 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-15817350

RESUMO

PURPOSE: This Phase II study was designed to determine the median survival time of adults with supratentorial glioblastoma treated with a combination of temozolomide (TMZ) and 13-cis-retinoic acid (cRA) given daily with conventional radiation therapy (XRT). METHODS AND MATERIALS: This was a single arm, open-labeled, Phase II study. Patients were treated with XRT in conjunction with cRA and TMZ. Both drugs were administered starting on Day 1 of XRT, and chemotherapy cycles continued after the completion of XRT to a maximum of 1 year. RESULTS: Sixty-one patients were enrolled in the study. Time to progression was known for 55 patients and 6 were censored. The estimated 6-month progression-free survival was 38% and the estimated 1-year progression-free survival was 15%. Median time to progression was estimated as 21 weeks. The estimated 1-year survival was 57%. The median survival was 57 weeks. CONCLUSIONS: The combined therapy was relatively well tolerated, but there was no survival advantage compared with historical studies using XRT either with adjuvant nitrosourea chemotherapy, with TMZ alone, or with the combination of TMZ and thalidomide. Based on this study, cRA does not seem to add a significant synergistic effect to TMZ and XRT.


Assuntos
Antineoplásicos Alquilantes/uso terapêutico , Dacarbazina/análogos & derivados , Glioblastoma/tratamento farmacológico , Glioblastoma/radioterapia , Neoplasias Supratentoriais/tratamento farmacológico , Neoplasias Supratentoriais/radioterapia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica , Terapia Combinada , Dacarbazina/administração & dosagem , Intervalo Livre de Doença , Feminino , Glioblastoma/mortalidade , Humanos , Isotretinoína/administração & dosagem , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Neoplasias Supratentoriais/mortalidade , Temozolomida
11.
Int J Radiat Oncol Biol Phys ; 60(2): 353-7, 2004 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-15380566

RESUMO

PURPOSE: The chemotherapeutic agent temozolomide (TMZ) and the antiangiogenic agent thalidomide have both demonstrated antitumor activity in patients with recurrent malignant glioma. The objectives of this study were to determine if the combined strategy of these oral agents with radiation therapy (RT) is associated with an improved median survival of patients with newly diagnosed glioblastoma multiforme and to evaluate toxicity. METHODS AND MATERIALS: Sixty-seven patients were enrolled in this trial. Radiotherapy parameters were a total dose of 60 Gy delivered in 2 Gy fractions over 6 weeks. Temozolomide was administered starting the first day of RT at 150 mg/m(2) daily for 5 days every 4 weeks for the first cycle and escalated to a maximum dose of 200 mg/m(2). Thalidomide was started on Day 7 of RT at 200 mg and escalated by 100-200 mg every 1-2 weeks depending on patient tolerance, to a maximum of 1,200 mg daily. RESULTS: Sixty-one patients have progressed, with a median time to progression of 22 weeks. Fifty-six patients have died, and the median survival was 73 weeks. CONCLUSIONS: This strategy of combination TMZ, thalid and RT was relatively well tolerated with favorable survival outcome for patients with GM when compared to patients not treated with adjuvant chemotherapy and similar to those who have received nitrosourea adjuvant chemotherapy. It is unclear the added advantage thalid has in combination with TMZ for this patient population.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/radioterapia , Dacarbazina/análogos & derivados , Glioblastoma/tratamento farmacológico , Glioblastoma/radioterapia , Adulto , Idoso , Inibidores da Angiogênese/administração & dosagem , Antineoplásicos Alquilantes/administração & dosagem , Neoplasias Encefálicas/mortalidade , Terapia Combinada , Dacarbazina/administração & dosagem , Esquema de Medicação , Feminino , Seguimentos , Glioblastoma/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Temozolomida , Talidomida/administração & dosagem
12.
Cancer ; 100(3): 605-11, 2004 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-14745879

RESUMO

BACKGROUND: Options for chemotherapy at the time of recurrence in patients with malignant glioma are limited. The authors describe the efficacy and safety results of their institution's open-label, compassionate-use protocol of temozolomide for patients with recurrent malignant glioma. METHODS: Patients with recurrent malignant glioma at any time during recurrence were treated with oral temozolomide at a dose of 150 mg/m2 per day on a 5-day schedule every 28 days. If this dose was tolerated, then escalation to 200 mg/m2 was allowed. Clinical evaluations and assessments of tumor response were performed every 2 months. All patients or their surrogates signed approved Institutional Review Board consent forms. RESULTS: Among 213 patients who were treated, 33% had Grade 3 tumors, and 67% had Grade 4 tumors. The overall objective response rate was 16% in both of these patient groups; and an additional 51% and 30% of patients with Grade 3 and Grade 4 tumors, respectively, had stable disease as their best response. The 6-month progression-free survival rates were 41% and 18% for patients with Grade 3 and Grade 4 tumors, respectively. The median survival was 49 weeks for patients with Grade 3 tumors and 32 weeks for patients with Grade 4 tumors. The major toxicity was hematologic toxicity. In multivariate analysis, the Karnofsky performance score was a significant predictor of survival for patients with Grade 4 tumors. CONCLUSIONS: Temozolomide was well tolerated in patients with recurrent malignant glioma and had modest efficacy, even at the time of multiple recurrences.


Assuntos
Antineoplásicos Alquilantes/administração & dosagem , Neoplasias Encefálicas/tratamento farmacológico , Dacarbazina/análogos & derivados , Dacarbazina/administração & dosagem , Glioma/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Adolescente , Adulto , Idoso , Biópsia por Agulha , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/patologia , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Seguimentos , Glioma/mortalidade , Glioma/patologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Probabilidade , Modelos de Riscos Proporcionais , Medição de Risco , Análise de Sobrevida , Temozolomida , Resultado do Tratamento
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