Sorafenib use in elderly patients with hepatocellular carcinoma: caution about use of platelet aggregation inhibitors.

PURPOSE: Sorafenib is the standard of care for advanced hepatocellular carcinoma (HCC). The peak incidence of HCC is around 70 years. We aimed to evaluate safety and efficacy of sorafenib in the elderly population. METHODS: We retrospectively reviewed data from patients treated with sorafenib for HCC at our institution. We compared safety and efficacy data across different age groups. RESULTS: Since 2005, 129 patients were treated, 78 (60.5 %) were <70 years old and 51 (39.5 %) were ≥70. The frequency of dose reduction was similar between the two groups (48.7 vs. 58.8 %), as was the occurrence of severe toxicities (41.0 vs. 51.0 %) and hospitalization due to toxicity (9.0 vs. 13.7 %). However, asthenia and bleeding were more frequent in the elderly. The higher frequency of bleeding was explained by concomitant antiplatelet treatments, and major asthenia was frequent in PS1 elderly patients. There was a trend toward less frequent interruption of treatment in the younger group (25.6 vs. 39.2 %) and significantly less frequent definitive discontinuation of treatment due to toxicity (24.4 vs. 45.1 %). Median progression-free survival was 5.6 months in both age groups, while median overall survival was 9.6 months in the younger age group and 12.6 months in the older age group. CONCLUSION: Sorafenib showed similar results in terms of safety and efficacy in the elderly and younger HCC populations. Careful baseline evaluation is needed for patient's selection in the elderly population, including discussion about antiplatelet therapy discontinuation and caution in PS1 patients, as well as active management of toxicity.

[Retrospective analysis of 24 recurrent glioblastoma after chemoradiation and treated with nitrosoureas or irinotecan and bevacizumab]. / Analyse rétrospective de 24 glioblastomes récidivant après radiochimiothérapie concomitante et traités par nitrosourées ou par l'association irinotécan et bévacizumab.

Despite progress in the initial management of glioblastoma (GB), the vast majority of patients will experience recurrence within 2-3 years. The medical treatment of these recurrences is being modified by the use of antiangiogenic therapies. Twenty-four patients, who relapsed from GB after chemoradiation followed by adjuvant temozolomide in Rennes, were treated by conventional chemotherapy (nitrosourea) or by the combination of irinotecan and bevacizumab. In this retrospective analysis, overall survival from diagnosis of recurrence was significantly longer in patients treated with the combination of bevacizumab and irinotecan than with nitrosourea (5 months versus 11.5 months). The combination of irinotecan and bevacizumab appeared to provide clinical benefit to patients with recurrent GB.

Usefulness of chemotherapy beyond the second line for metastatic breast cancer: a therapeutic challenge.

PURPOSE: Several lines of chemotherapy can be proposed for patients with metastatic breast cancer, but beyond the second line, agreement is lacking concerning the most appropriate therapeutic strategy. METHODS: We conducted a retrospective analysis of the files of 162 patients, who had received at least 3 lines of chemotherapy (CT3) for metastatic breast cancer during a 5-year period (2000-2004), in order to analyze management practices and search for factors affecting survival from CT3 and predictive factors of non-progressive disease (NPD) after CT3. RESULTS: Multivariate analysis identified seven factors which had a positive influence on survival from CT3 (SBR grade I, absence of adjuvant hormone therapy, free interval >or=2 years, absence of cerebromeningeal metastasis before CT, unique focus at initiation of CT3, use of polychemotherapy for CT2, and complete response to CT1 or CT2) and two predictive factors of NPD (histology and drug group used for CT3). CONCLUSIONS: These factors should help determine the appropriate strategy for proposing a third line of chemotherapy.

Topotecan in combination with radiotherapy in unresectable glioblastoma: a phase 2 study.

Improving glioblastoma multiforme (GBM) treatment with radio-chemotherapy remains a challenge. Topotecan is an attractive option as it exhibits growth inhibition of human glioma as well as brain penetration. The present study assessed the combination of radiotherapy (60 Gy/30 fractions/40 days) and topotecan (0.9 mg/m(2)/day on days 1-5 on weeks 1, 3 and 5) in 50 adults with histologically proven and untreated GBM. The incidence of non-hematological toxicities was low and grade 3-4 hematological toxicities were reported in 20 patients (mainly lymphopenia and neutropenia). Partial response and stabilization rates were 2% and 32%, respectively, with an overall time to progression of 12 weeks. One-year overall survival (OS) rate was 42%, with a median OS of 40 weeks. Topotecan in combination with radiotherapy was well tolerated. However, while response and stabilization concerned one-third of the patients, the study did not show increased benefits in terms of survival in patients with unresectable GBM.

Malignant transformation of intra-cranial epithelial cysts: systematic article review.

INTRODUCTION: Epidermoid and dermoid cysts are among the most benign intra cranial tumors. Their malignant transformation into squamous cell carcinoma is rare. The authors reviewed the literature. MATERIALS AND METHODS: MEDLINE and SCIENCE DIRECT searches, and examination of the references in the selected articles yielded 74 patients, 52 of whom fulfilled Garcia's criteria and were selected for the study. Survival analyses were performed to determine whether survival differences were of statistical significance, and P < 0.05 was considered as significant. RESULTS: Malignant transformation is characterized by a rapid onset of symptoms, recurrence, leptomeningeal carcinomatosis (LC), and tumor enhancement at Computed Tomography Scan or Magnetic Resonance Imaging (87.8 showed this radiological feature). In this review, the SCCs were classified in five groups: (1) Initial malignant transformation of a benign cyst; (2) malignant transformation from a remnant cyst; (3) malignant transformation of a dermoid and epithelial cyst; (4) malignant transformation with leptomeningeal carcinomatosis; (5) other malignancies arising from benign cysts. The median survival was 9 months. Statistics show that LC was of poor prognosis and radiotherapy, although not statistically significant, seems effective against such lesions, with a median survival of 26 months as opposed to 3 months (P=0.077). CONCLUSION: Although rare, malignant transformation of intracranial epithelial cysts has a poor prognosis and surgery followed by radiotherapy seems to be the best therapeutic modality.

Oligodendroglioma: clinical study and survival analysis correlated with chromosomal anomalies.

OBJECT: Demonstration of the loss of chromosomes 1p and 19q in the presence of a brain neoplasm marks the emergence of genotype as a prognostic indicator. The authors report gene expression data for oligodendroglioma and correlate genotype with response to therapy. Gene expression subgroups may represent distinct types of disease. METHODS: Eighty-seven cases of supratentorial oligodendroglioma were selected from 145 cases treated in a single center between January 1990 and December 2001. Fluorescence in situ hybridization was used to determine the status of chromosomes 1p and 19q. Parameters evaluated included clinical data and radiological and histological features. Univariate and multivariate analyses were performed and a probability value less than 0.05 was considered significant. The patients included 48 women and 39 men. The overall mean age at presentation was 45 years for women and 36 years for men (p = 0.006). The univariate analysis identified the following as favorable prognostic factors: younger patient age (p = 10(-5)), female sex (p = 0.0025), seizure as a presenting symptom (p = 10(-5)), normal clinical examination (p = 10(-5)), absence of lesion enhancement on neuroimaging studies (p = 0.0231), lack of histological necrosis (p = 0.0003), absence of mitoses (p = 0.0014), 1p and 19q deletions (p = 0.0001), absence of recurrence (p = 0.0021), and adjuvant radiotherapy and/or chemotherapy (p = 10(-5)). The multivariate analysis identified patient age (p = 10(-5)) and chromosomal anomalies (p = 0.002) as independently linked to survival. Three molecular subtypes emerged: oligodendroglioma with 1p and 19q deletions, oligodendroglioma demonstrating polysomia and a lack of meaningful response to radiotherapy or chemotherapy, and oligodendroglioma with no 1p-9q deletion in which partial response was seen. CONCLUSIONS: According to our data, oligodendrogliomas could be divided into three molecular subtypes. Although chemotherapy seems efficient for managing this tumor, additional studies should be conducted to compare the efficacy of radiotherapy and chemotherapy.

Phase I study of topotecan in combination with concurrent radiotherapy in adults with glioblastoma.

A phase I study was performed to determine the maximum tolerated dose and the recommended dose of continuous intravenous infusion of topotecan in combination with radiotherapy (RT) in patients with previously untreated glioblastoma multiforme (GBM). Twenty patients with histologically proven GBM and 1 with rhabdoid tumor were enrolled. After surgery or stereotactic biopsy, patients received cranial RT (60 Gy/30 fractions/40 days) and 3 cycles of topotecan as continuous infusion (CIV) from day 1 to 5 on weeks 1, 3, and 5 during RT. The dose of topotecan was escalated from 0.6 to 1.0 mg/m2/day. Four dose levels were tested. One grade 4 thrombocytopenia was seen at level 1 (topotecan dose 0.6 mg/m2/day; 6 patients). No dose-limiting toxicity was seen at level 2 (0.8 mg/m2/day; 3 patients) or an intermediate level of 2 bis (0.9 mg/m2/day; 6 patients). Six patients were included at level 3 (1.0 mg/m2/day), 4 of whom experienced dose-limiting toxicities, including 3 episodes of grade 4 thrombocytopenia, 1 platelet transfusion, 1 febrile neutropenia, and 1 grade 4 neutropenia of more than 7 days. Eighty percent of patients with GBM were alive at 12 months. The dose-limiting toxicity of topotecan administered as CIV for 5 days every 2 weeks is hematological. The maximum tolerated dose is 1.0 mg/m2/day and the recommended dose is 0.9 mg/m2/day. A phase II trial using the recommended dose of topotecan is ongoing.