Post-operative combined radiation and chemotherapy with temozolomide and irinotecan in patients with high-grade astrocytic tumors. A phase II study with biomarker evaluation

Background: Clinical studies have shown that temozolomide (TMZ) and irinotecan demonstrate activity in high grade astrocytic tumors (HGAT). However, the optimal schedule of administration is unknown. Patients and Methods: In the present study, a total of 45 HGAT patients, 38 with glioblastoma multiforme (GBM) and 7 with anaplastic astrocytoma (AA), were treated with TMZ, 150 mg/m(2) on days 1-5, followed by irinotecan, 150 mg/m(2) on days 6 and 17, every 4 weeks,for 6 cycles or until the occurrence of unacceptable toxicity or disease progression. Radiation therapy (60 Gy) was initiated on the first day of treatment. Results: Twenty-two patients completed six cycles of treatment. Most frequently recorded side-effects included neutropenia (37%), nausea/vomiting (66%), diarrhea (31%) and infection (44%). Five episodes of vaso-occlusive disease, all of them fatal, were observed. After a median follow-up of 49.8 months, median progression-free survival for patients with GBM was 7.7 months, while median overall survival was 12.8 months. There were six long-term survivors, three of them with GBM. Two out of the five biomarkers studied, epidermal growth factor receptor (EGFR) and vascular endothelial growth factor-C (VEGF-C), were found to be overexpressed in 74% of the tumors, however they had no predictive value for progression-free or overall survival. Conclusion: The combination of TMZ and irinotecan, as administered in this study, was accompanied by high rates of toxicity, especially myelotoxicity and infection. Further development of this regimen in the treatment of HGAT is not recommended

Additional file 2: of A systematic review of the risk factors for clinical response to opioids for all-age patients with cancer-related pain and presentation of the paediatric STOP pain study

BMC Cancer.doc, Characteristics of the 74 studies included in the review. (RTF 506 kb

Effect of intravenous corticosteroids on death within 14 days in 10008 adults with clinically significant head injury (MRC CRASH trial): randomised placebo-controlled trial.

BACKGROUND: Corticosteroids have been used to treat head injuries for more than 30 years. In 1997, findings of a systematic review suggested that these drugs reduce risk of death by 1-2%. The CRASH trial--a multicentre international collaboration--aimed to confirm or refute such an effect by recruiting 20000 patients. In May, 2004, the data monitoring committee disclosed the unmasked results to the steering committee, which stopped recruitment. METHODS: 10008 adults with head injury and a Glasgow coma score (GCS) of 14 or less within 8 h of injury were randomly allocated 48 h infusion of corticosteroids (methylprednisolone) or placebo. Primary outcomes were death within 2 weeks of injury and death or disability at 6 months. Prespecified subgroup analyses were based on injury severity (GCS) at randomisation and on time from injury to randomisation. Analysis was by intention to treat. Effects on outcomes within 2 weeks of randomisation are presented in this report. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN74459797. FINDINGS: Compared with placebo, the risk of death from all causes within 2 weeks was higher in the group allocated corticosteroids (1052 [21.1%] vs 893 [17.9%] deaths; relative risk 1.18 [95% CI 1.09-1.27]; p=0.0001). The relative increase in deaths due to corticosteroids did not differ by injury severity (p=0.22) or time since injury (p=0.05). INTERPRETATION: Our results show there is no reduction in mortality with methylprednisolone in the 2 weeks after head injury. The cause of the rise in risk of death within 2 weeks is unclear