Biomedical subjects

A A Brandes

Publications and source records attributed to A A Brandes.

At least 19 recordsLinked to original sources

PubMed2006

Temozolomide 3 weeks on and 1 week off as first-line therapy for recurrent glioblastoma: phase II study from gruppo italiano cooperativo di neuro-oncologia (GICNO).

The efficacy of temozolomide strongly depends on O(6)-alkylguanine DNA-alkyl transferase (AGAT), which repairs DNA damage caused by the drug itself. Low-dose protracted temozolomide administration can decrease AGAT activity. The main end point of the present study was therefore to test progression-free survival at 6 months (PFS-6) in glioblastoma patients following a prolonged temozolomide schedule. Chemonaïve glioblastoma patients with disease recurrence or progression after surgery and standard radiotherapy were considered eligible. Chemotherapy cycles consisted of temozolomide 75 mg/m(2)/daily for 21 days every 28 days until disease progression. O(6)-methyl-guanine-DNA-methyl-tranferase (MGMT) was determined in 22 patients (66.7%). A total of 33 patients (median age 57 years, range 31-71) with a median KPS of 90 (range 60-100) were accrued. The overall response rate was 9%, and PFS-6 30.3% (95% CI:18-51%). No correlation was found between the MGMT promoter methylation status of the tumours and the overall response rate, time to progression and survival. In 153 treatment cycles delivered, the most common grade 3/4 event was lymphopoenia. The prolonged temozolomide schedule considered in the present study is followed by a high PFS-6 rate; toxicity is acceptable. Further randomised trials should therefore be conducted to confirm the efficacy of this regimen.

Adult↗

PubMed2006

MATILDE regimen followed by radiotherapy is an active strategy against primary CNS lymphomas.

The authors assessed MATILDE chemotherapy followed by response-tailored radiation therapy in 41 patients aged 70 years or younger with primary CNS lymphoma in a Phase II trial. With response rates of 76% after MATILDE and 83% after chemotherapy with or without radiation therapy, this was an active strategy, particularly in low- to intermediate-risk patients (International Extranodal Lymphoma Study Group [IELSG] score). Myelosuppression was the dose-limiting toxicity, with 9.5% of lethal complications. After a median follow-up of 49 months, a plateau in the survival curve (5-year overall survival: 41 +/- 7%) was obtained.

Adolescent↗

PubMed2006

Raltitrexed-eloxatin salvage chemotherapy in gemcitabine-resistant metastatic pancreatic cancer.

Limited information on salvage treatment in patients affected by pancreatic cancer is available. At failure, about half of the patients present good performance status (PS) and are candidate for further treatment. Patients >18 years, PS >or=50, with metastatic pancreatic adenocarcinoma previously treated with gemcitabine-containing chemotherapy, and progression-free survival (PFS) <12 months received a combination of raltitrexed (3 mg m(-2)) and oxaliplatin (130 mg m(-2)) every 3 weeks until progression, toxicity, or a maximum of six cycles. A total of 41 patients received 137 cycles of chemotherapy. Dose intensity for both drugs was 92% of the intended dose. Main grade >2 toxicity was: neutropenia in five patients (12%), thrombocytopenia, liver and vomiting in three (7%), fatigue in two (5%). In total, 10 patients (24%) yielded a partial response, 11 a stable disease. Progression-free survival at 6 months was 14.6%. Median survival was 5.2 months. Survival was significantly longer in patients with previous PFS >6 months and in patients without pancreatic localisation. A clinically relevant improvement of quality of life was observed in numerous domains. Raltitrexed-oxaliplatin regimen may constitute a treatment opportunity in gemcitabine-resistant metastatic pancreatic cancer. Previous PFS interval may allow the identification of patients who are more likely to benefit from salvage treatment.

Adult↗

PubMed2006

Is protracted low-dose temozolomide feasible in glioma patients?

The authors investigated the safety of 75 mg/m2 temozolomide for 21 days every 28 days in glioma patients. This schedule could lead to DNA repair enzyme O6-alkylguanine-DNA alkyltransferase depletion, contributing to overcoming drug resistance. Although Phase III studies are forthcoming, no data are available on the long-term toxicity of temozolomide, which, in this series, incurred prolonged, cumulative lymphopenia, which leads to a high incidence of infections.

Adult↗

PubMed2005

Relationship between prognostic factors of breast cancer and 99mTc-sestamibi uptake in patients who underwent scintimammography: Multivariate analysis of causes of false-negative results.

The complementary role of sestamibi scintimammography (SSM) in patients with breast cancer (BC) is well established. The aim of this study was to establish whether a relationship exists between sestamibi uptake, evaluated as a tumour-to-background ratio (TBR), and the main prognostic factors of BC. SSM with the measurement of TBR was performed preoperatively in 102 women (median age 57 years, range 32-81 years) who underwent curative surgery for primary BC. Final pathology showed 4 (3.9%) with pT1a, 17 (16.7%) with pT1b, 44 (43.1%) with pT1c and 37 (36.3%) with pT2 breast carcinomas. The overall sensitivity of SSM was 80.4%. An ANOVA showed significant (P<0.01) differences between the TBR of patients with G1 vs. G3 tumours, and between the TBR of those with G2 vs. G3 breast carcinomas. Moreover, there was a difference (P=0.021) between the TBR of patients (n=12, 11.8%) with CEA serum levels >10 ng/ml (2.031+/-0.420), and those with normal (n=90, 88.2%) CEA values (1.713+/-0.446), whilst no difference (P=NS) was found between patients (n=27, 26.5%) with CA 15-3 >30 U/ml (1.893+/-0.401) and those with normal (n=75, 73.5%) CA 15-3 values (1.699+/-0.462). There was a mild inverse correlation between TBR and both the oestrogen (R=0.25, P=0.011) and the progesterone receptor (R=0.23, P=0.02) rate. The logistic regression analysis showed that only size and CA 15-3 serum levels represent true independent parameters, but the function was able to predict only 11 out of 21 (52.4%) patients with false-negative SSM. TBR is independent of age and mainly correlates with the size of the tumour. There are no reliable preoperative prognostic factors that are really useful for improving SSM sensitivity in patients with small breast carcinomas.

Adult↗

PubMed2004

How effective is BCNU in recurrent glioblastoma in the modern era? A phase II trial.

BACKGROUND: The initial studies on nitrosoureas were performed >30 years ago. These drugs remain the standard chemotherapy for glioblastoma. However, because the criteria used to evaluate the activity of nitrosoureas in a neuro-oncologic setting have changed, new data on their activity are needed. METHODS: The authors conducted a phase II study on 40 patients with recurrent glioblastoma following surgery and standard radiotherapy. They analyzed progression-free survival at 6 months (PFS-6), time to progression (TTP), response rate, and toxicity. Patients were treated with 80 mg/m2 carmustine on days 1 to 3, every 8 weeks for a maximum of six cycles. RESULTS: Median TTP was 13.3 weeks (95% CI, 10.26 to 16.86 weeks), and PFS-6 was 17.5% (95% CI, 8.9 to 34.3). Response to chemotherapy, age < or =40 years, and performance status > or =90 were significant prognostic factors for TTP; however, with multivariate analysis, only response to chemotherapy was significant. The major side effects were reversible hematologic and long-lasting hepatic and pulmonary toxicity. CONCLUSION: The activity of this BCNU regimen is comparable with that reported in the past and with the newest therapies, such as temozolomide. However, BCNU toxicity is high and recovery is slow, thus compromising the administration of further drugs in patients with progressive disease.

Adult↗

PubMed2004

Salvage PCV chemotherapy for temozolomide-resistant oligodendrogliomas.

The authors investigated the results of PCV chemotherapy within a cohort of 24 patients treated within the EORTC study 26971 on temozolomide chemotherapy in recurrent oligodendroglioma. The genotype of the tumors was assessed with fluorescent in situ hybridization with locus specific probes for the region 1p36. Four of the 24 patients responded (17%). Fifty percent of patients were still free from progression at 6 months and 21% were free from progression at 12 months. Although a clear relation existed between loss of 1p and response to temozolomide chemotherapy, this relation was absent in salvage PCV chemotherapy.

Adult↗

PubMed2004

Seroma prevention following axillary dissection in patients with breast cancer by using ultrasound scissors: a prospective clinical study.

AIMS: Seroma formation following axillary dissection is a common complication of breast surgery. The aims of this study were (1) to analyse the risk factors of seroma formation, and (2) to evaluate the role of ultrasound scissors in performing axillary dissection in patients with primary breast cancer undergoing mastectomy and breast-conserving surgery. METHODS: Ninety-two women (median age 55 years, range 33-73 years) requiring surgery for known unilateral primary breast cancer (pT1a=1, pT1b=20, pT1c=43, pT2=25, pT3=3) were prospectively randomised to undergo axillary dissection by either using (Group A, 45 patients) or not using (Group B, 47 patients) ultrasound scissors (US). Thirty-eight (41.3%) patients underwent modified radical mastectomy, while 54 (58.7%) underwent breast-conserving surgery. RESULTS: Twenty-eight (30.4%) patients (Group A=9 out of 45, 20%; Group B=19 out of 47, 42%; P=NS) developed a wound seroma. Multivariate analysis using a logistic regression model showed that surgical procedure (RR=8.9; 95% CI: 3.2-25.3), total amount of drainage (RR=7.8; 95% CI: 2.8-22.0), and size of the tumour (RR=6.0; 95% CI: 2.2-16.5) independently correlated with seroma formation. The logistic regression function (RR=19.4; 95% CI: 6-62) correctly allocated 75 out of 92 (81.5%) patients. CONCLUSIONS: Size of the tumour, and total amount of drainage represent the principal factors of seroma formation following axillary dissection in patients undergoing surgery for breast cancer. Although the use of ultrasound cutting devices may reduce the risk of seroma formation, further studies are need to verify the real impact on long-term morbidity of such technique.

Adult↗

PubMed2004

Current and future trials of the EORTC brain tumor group.

The EORTC Brain Tumor Group (BTG) is dedicated to clinical research of neoplasms of the brain. In the past years the BTG has carried out phase II and phase III trials on glial tumors, brain metastases and primary CNS lymphomas. Future studies will investigate novel drugs in combination with chemo-radiotherapy in glioblastoma multiforme, radiotherapy in meningioma, and chemotherapy in medulloblastoma. The BTG will also start a new phase III trial on newly diagnosed low-grade glioma comparing radiotherapy to temozolomide. In all our trials translational research is getting more and more important, often this is one of the most important ways to get useful conclusions from clinical trials. The wide recognition of the importance of translational research for clinical trials and in particular with targeted therapies implies that this type of research will become a mandatory element in many of our future trials.

Antineoplastic Agents↗

PubMed2003

Phase II study of first-line chemotherapy with temozolomide in recurrent oligodendroglial tumors: the European Organization for Research and Treatment of Cancer Brain Tumor Group Study 26971.

PURPOSE: Oligodendroglial tumors are chemotherapy-sensitive tumors, with two thirds of patients responding to combination chemotherapy with procarbazine, lomustine, and vincristine (PCV). Temozolomide (TMZ), a new alkylating and methylating agent, has demonstrated high response rates in patients with recurrent anaplastic astrocytoma. We investigated TMZ as first-line chemotherapy in recurrent oligodendroglial tumors (OD) and mixed oligoastrocytomas (OA) after surgery and radiation therapy. PATIENTS AND METHODS: In a prospective, nonrandomized, multicenter, phase II trial, patients were treated with 200 mg/m2 of TMZ on days 1 through 5 in 28-day cycles for 12 cycles. Patients with a recurrence after prior surgery and radiotherapy, and with measurable and enhancing disease on magnetic resonance imaging (MRI) were eligible for this study. Patients with large lesions and mass effect or with new clinical deficits were not eligible. Pathology and the MRI scans of all responding patients were centrally reviewed. RESULTS: Thirty-eight eligible patients were included. In three patients, pathology review did not confirm the presence of an OD or OA. TMZ was generally well tolerated. The most frequent side effects were hematologic; only one patient discontinued treatment for toxicity. In 20 (52.6%) of 38 patients (95% exact confidence interval, 35.8% to 69.0%), a complete (n = 10) or partial response to TMZ was observed. The median time to progression was 10.4 months for all patients and 13.2 months for responding patients. At 12 months from the start of treatment, 40% of patients were still free from progression. CONCLUSION: TMZ provides an excellent response rate with good tolerability in chemotherapy-naive patients with recurrent OD. A randomized phase III study comparing PCV with TMZ is warranted.

Adult↗

PubMed2003

Carboplatin and teniposide as third-line chemotherapy in patients with recurrent oligodendroglioma or oligoastrocytoma: a phase II study.

BACKGROUND: This study was a phase II study of third-line chemotherapy with carboplatin plus teniposide in patients with recurrent oligodendroglioma. PATIENTS AND METHODS: Patients with oligodendroglioma progressive or recurrent after surgery, radiotherapy and chemotherapy with PCV (lomustine/procarbazine/vincristine) and temozolomide were treated with 350 mg/m(2) carboplatin on day 1, and 50 mg/m(2) teniposide on days 1-3, every 4 weeks. RESULTS: Response and toxicity were evaluated in all 23 patients enrolled in the study. Two had partial response [8.6%; 95% confidence interval (CI) 1.8% to 28.6%] and 12 stable disease (52.17%; 95% CI 30% to 73%). Median time to progression was 19 weeks (95% CI 11.4-35.0), and 34.8% of the patients (95% CI 20.0% to 61.0%) had progression-free survival at 6 months. Median survival time was 60.7 weeks (95% CI 39.8 to not achieved) and 51% of the patients (95% CI 33.5% to 79.7%) were alive at 12 months. A total of 103 cycles were administered (on average 4.4 per patient; range 1-9). Toxicity was mild and mainly hematological, with grade 4 neutropenia and grade 4 thrombocytopenia in two (8.6%) and three patients (13%), respectively. CONCLUSIONS: Although the response rate of combined carboplatin and teniposide chemotherapy in heavily pretreated oligodendroglial tumors is moderate, the toxicity is manageable, and delay of progression in responders or stable patients may still confer a relevant clinical benefit.

Adult↗

PubMed2003

Guidelines for the management and treatment of low-grade gliomas.

Treatment options for low-grade gliomas are a challenging dilemma in neuro-oncology. Young age at onset, low rate of growth and long-term treatment sequelae, indicate that minimally invasive treatments are required. However, local recurrence and conversion to malignant glioma occur within 4 to 8 yrs after diagnosis, calling for adjuvant treatment strategies, such as RT and chemotherapy with the aim of improving the disease-free interval. As glioma has a low incidence, and few randomised trials are available in literature, there is little consensus on the correct timing and dosage for RT, or on indications for timing and choice of cytotoxic drugs administration. The present paper therefore focuses on current concepts and future perspectives in the treatment options for low-grade gliomas.

Journal Article↗

PubMed2003

Guidelines for the treatment of malignant gliomas in elderly patients.

More than 80% of intracranial tumours in the elderly are malignant gliomas with aggressive behaviour. Older patients have been frequently excluded from clinical trials in view of their dismal prognosis and low tolerability of chemo-radiotherapy treatments, therefore they were underrepresented in the past oncological literature. Controversies in the use and dose of RT and in the administration of chemotherapeutic agents have not been solved by the small retrospective studies conducted so far. It appears reasonable that an aggressive treatment with surgery, full dose RT and, possibly, chemotherapy should be applied to patients with good performance status, preserved cognitive functions and no relevant comorbidities, although in the absence of randomised studies the balance of benefits and side effects of integrated treatments remains controversial. Patients with low performance status and/or serious comorbidities, unable to undergo surgery, may receive a shorter RT plan, or even no treatment at all, in consideration of the rapid course of their disease which may be shorter than the hypothetical benefit of any specific treatment. Further studies should be designed to perform a reliable analysis of prognostic factors of malignant gliomas in the elderly in order to tailor treatments to each patient to obtain the best feasible benefit without compromising their quality of life.

Journal Article↗

PubMed2003

Current and future strategies in the management of medulloblastoma in adults.

Medulloblastoma in adults are rare and differ from their childhood counterparts in terms of tumor site (hemispheric location), histological subtype (desmoplastic variant), lower incidence of metastatic spread and frequent late relapses. As in children the presence of metastatic disease is of major prognostic significance. The role of different histological subtypes and molecular genetic/biological markers is unknown and deserves further investigations. The therapeutic strategies are essentially based on experiences in childhood medulloblastomas. Surgery followed by irradiation of the entire central nervous system followed by a boost to the posterior fossa is the cornerstones of treatment. A sufficient dose prescription and a high quality of treatment are a prerequisite for an optimal tumor control. Unlike in children the role of chemotherapy is an open question and requires prospective investigations. The forthcoming EORTC-study is addressing this issue.

Journal Article↗

PubMed2002

A multidrug combination designed for reversing resistance to BCNU in glioblastoma multiforme.

BACKGROUND: Nitrosoureas constitute the main resource of chemotherapy for glioblastoma. However, because of chemoresistance, which is intrinsic or rapidly acquired after the first administration of chemotherapy, there have been few improvements in survival. Because O(6)-alkylguanine-DNA alkyltransferase (AGT) is the main target for increasing cell sensitivity to the nitrosoureas, we postulated that preexposure to other alkylating agents might increase the therapeutic index of the nitrosoureas by saturating all the copies of AGT present in the tumor cells. OBJECTIVE: To investigate the response rate, toxic effects, time from start of chemotherapy to progression of disease or exit from the study for any reason (TTP), and progression-free survival at 6 months (PFS-6) associated with a multidrug combination that could reverse resistance to carmustine (BCNU) through AGT depletion. METHODS: We conducted a phase 2 study of patients with glioblastoma at first relapse or progression after surgery and standard radiotherapy. Patients were treated with 100 mg/m(2) of procarbazine on days 1 to 5, 80 mg/m(2) of BCNU on days 3 to 5, and 1.4 mg/m(2) of vincristine on day 3 every 8 weeks. RESULTS: Fifty-eight patients were enrolled in the study, and all were assessable for response and toxic effects. Six patients (10.3%) had a complete response, 11 (19%) had a partial response, and 17 (29.3%) had stable disease. The median TTP was 4.8 months; 42.3% of patients had PFS-6, and 15.4% had PFS at 12 months. Response to chemotherapy was the only significant prognostic factor for TTP. Neutropenia was grade 3 in 8.6% of patients and grade 4 in 5.2% of patients, and thrombocytopenia was grade 3 in 17.2% of patients and grade 4 in 12% of patients; hepatic and pulmonary toxic effects were grade 3 in 5.2% and 8.6% of patients, respectively. CONCLUSION: This regimen proved active in chemotherapy-naive patients with recurrent glioblastoma even though toxic effects were substantial.

Adolescent↗

PubMed2002

Breast complaints and risk of breast cancer. Population-based study of 2,879 self-selected women and long-term follow-up.

The aim of this study was to provide information about risk of breast cancer (BC) in women with breast complaints undergoing spontaneously clinical examination. The records of 2,879 self-selected symptomatic new patients observed consecutively were reviewed, and the chief breast complaint such as pain, lump and nipple discharge had been recorded. Patients were divided in three groups: Group A, 1,186 (41.2%) patients aged < 41 years; Group B, 809 (28.1%) patients aged 41-55 years; and Group C, 884 (30.7%) patients aged > 55 years. Pain was most common (P < 0.01) in Group A (60.8%), and lump in Groups B (53.3%) and C (89.7%). A total of 318 (11.0%) women had histologically confirmed BC (Group A = 3.5%, Group B = 30.5%, Group C = 66.0%), accounting for 3.2, 16.4 and 12.0% of patients with pain, lump and nipple discharge, respectively. Breast complaints were equally (P= NS) distributed between patients with and without BC. The relative risk (RR) of BC developing ranged between 0.5-1.4, 0.5-1.9, and 0.6-3.0 in Groups A, B, and C, respectively. It ranged between 0.3 and 0.7 in patients with breast pain, and was significantly higher (RR = 1.9-3.0) only in patients with breast lump aged > 40 years. In conclusion, in symptomatic patients BC risk is strictly related to age, and independent of the referred symptoms. Therefore, further investigations have to be warranted only when risk factors different from breast complaints are present.

Adult↗

PubMed2002

Breast cancer risk in healthy and symptomatic women: results of a multivariate analysis. A case-control study.

Several risk factors for breast cancer (BC) have been investigated in different reports, but none has been really useful in preventing BC development. The aim of this study was to evaluate the risk of BC in self-selected symptomatic women in comparison with the healthy population residing in an urban area of Italy. A group of 404 women (median age 59 years, range 26-89 years) with confirmed BC (cases) were age-matched with 389 healthy women (Group A), and 391 (Group B) symptomatic non-screened patients without BC, who were referred to our Breast unit. The results of univariate analysis showed a significant (P < 0.01) difference between cases and controls in (1) age at menarche, (2) number of birth and age at first births, (3) lactation and months of lactation, and (4) estrogen replacement therapy (ERT) and duration of ERT. Multivariate analysis using a logistic regression model adjusted for age showed that five independent parameters (no pregnancy, age at first birth > 30 years, no lactation, use of ERT, ERT > 40 months) significantly (P < 0.01) correlated with BC onset. The relative odds ratios (ORs) at 95% confidence interval (95% CI) were 5.25, 2.47, 2.82, 2.80, and 5.56, respectively. The cumulative OR (95% CI) calculated from the observed vs. predicted values was 7.15. No differences (P = NS) were found between groups A and B. In conclusion, in our study population, the prolonged use (> 40 months) of ETR in menopausal women resulted in an increased risk of BC, and represented the only risk factor that could be removed.

Adult↗

PubMed2002

Diagnostic advances and new trends for the treatment of primary central nervous system lymphoma.

Primary central nervous system lymphoma (PCNSL) is a rare non-Hodgkin's lymphoma arising in the brain. Recent increase in its incidence has been noted both in immunocompetent individuals and patients with immunodeficiency. This review will focus on the epidemiology, pathogenesis, diagnosis and treatment of this aggressive extranodal lymphoma in immunocompetent patients. Stereotactic biopsy is usually required for diagnosis, while molecular biology and/or cytofluorimetric analysis may confirm the presence of clonal proliferation in the cerebrospinal fluid (CSF). Methotrexate-based chemotherapy plus whole-brain radiotherapy are the standard treatment for PCNSL and achieve a high rate of complete remissions (CR), but long-term neurotoxicity may heavily compromise the patient's quality of life. The metabolic rate of controversial gadolinium-enhancing lesions on magnetic resonance (MR) scans may be assessed with positron emission tomography (PET), which discriminates radiation necrosis from true recurrence. Withholding radiotherapy in patients achieving CR after first-line chemotherapy is a new and interesting treatment option, while the role of high-dose chemotherapy with stem cell rescue is still uncertain.

Antimetabolites, Antineoplastic↗