Toxicity and efficacy of lomustine and bevacizumab in recurrent glioblastoma patients.

The combination of lomustine and bevacizumab is a commonly used salvage treatment for recurrent glioblastoma (GBM). We investigated the toxicity and efficacy of lomustine plus bevacizumab (lom-bev) in a community-based patient cohort and made a comparison to another frequently used combination therapy consisting of irinotecan plus bevacizumab (iri-bev). Seventy patients with recurrent GBM were treated with lomustine 90 mg/m2 every 6 weeks and bevacizumab 10 mg/kg every 2 weeks. Toxicity was registered and compared to the toxicity observed in 219 recurrent GBM patients who had previously been treated with irinotecan 125 mg/m2 and bevacizumab 10 mg/kg every 2 weeks. The response rate was 37.1% for lom-bev and 30.1% for iri-bev. Median progression-free survival (PFS) was 23 weeks for lom-bev and 21 weeks for iri-bev (p = 0.9). Overall survival (OS) was 37 weeks for lom-bev and 32 weeks for iri-bev (p = 0.5). Lom-bev caused a significantly higher frequency of thrombocytopenia (11.4% grade 3-4) compared to iri-bev (3.5% grade 3-4). Iri-bev patients had more gastrointestinal toxicity with regard to nausea, vomiting, diarrhea, constipation and stomatitis. Within the limitations of the study lom-bev is a well-tolerated treatment for recurrent GBM, although hematological toxicity may be a dose limiting factor. No significant differences between lom-bev and iri-bev were observed with regard to PFS or OS. The differences in toxicity profiles between lom-bev and iri-bev could guide treatment decision in recurrent GBM therapy as efficacy is equal and no predictive factors for efficacy exist.

Treatment with docetaxel and cisplatin in advanced adrenocortical carcinoma, a phase II study.

BACKGROUND: Adrenocortical carcinoma (ACC) is a rare disease with a poor response to chemotherapy. Cisplatin is the most widely investigated drug in the treatment of ACC and in vitro studies have indicated activity of taxanes. The objectives of this study were to evaluate the efficacy and toxicity of cisplatin combined with docetaxel as first-line treatment of advanced ACC. METHODS: Patients with advanced ACC were included in this phase II trial investigating the response to a combination of cisplatin (50 mg m(-2)) and docetaxel (60 mg m(-2)) administered with a 3-week interval. RESULTS: Nineteen patients were included in this study. The response rate was 21% (95% CI: 3-39%). No patients obtained a complete response, 32% had stable disease, and 37% progressed while on treatment. The median progression-free survival (PFS) was 3 months (95% CI: 0.7-5.3 months) and 1 year PFS was 21% (95% CI: 3-39%). Median survival was 12.5 months (95% CI: 6-19 months). The predominant grade 3/4 toxicity was neutropenia (35%); febrile neutropenia occurred in 5% of cycles. CONCLUSION: This study could not demonstrate that the combination of cisplatin and docetaxel has higher efficacy than other regimens reported in previous studies.

A comprehensive profile of recurrent glioblastoma.

In spite of relentless efforts to devise new treatment strategies, primary glioblastomas invariably recur as aggressive, therapy-resistant relapses and patients rapidly succumb to these tumors. Many therapeutic agents are first tested in clinical trials involving recurrent glioblastomas. Remarkably, however, fundamental knowledge on the biology of recurrent glioblastoma is just slowly emerging. Here, we review current knowledge on recurrent glioblastoma and ask whether and how therapies change intra-tumor heterogeneity, molecular traits and growth pattern of glioblastoma, and to which extent this information can be exploited for therapeutic decision-making. We conclude that the ability to characterize and predict therapy-induced changes in recurrent glioblastoma will determine, whether, one day, glioblastoma can be contained in a state of chronic disease.