What can be done to improve patient safety in phase I trials?
- PDF / 128,601 Bytes
- 1 Pages / 595.245 x 841.846 pts (A4) Page_size
- 18 Downloads / 166 Views
More focus on late toxicities for MTAs? Researchers from France analysed toxicity data for 445 patients participating in 36 eligible phase I trials of MTAs.1 Median treatment duration was 55 days, with 15% of patients receiving ≥ 6 cycles. A total of 790 and 1819 toxic events were recorded during and after the first cycle, respectively. The majority of grade 3–4 toxic events (57%) occurred after the first cycle, with only 50% of patients experiencing their ‘worst grade’ toxicity during the first cycle. The researchers contend that moderate and severe toxicities "occur regularly" after the first cycle in phase I trials of MTAs and "may deserve increased attention" in the recommended phase II dose process for these agents which are administered ’in a chronic fashion". Another group of researchers retrospectively analysed toxicity risk for 173 patients treated with MTAs within a phase I trial, "as this therapeutic approach is becoming increasingly relevant".2 Forty grade 3 (23% of patients) and three grade 4 (1.7%) treatment-related events occurred, along with one treatment-related death (mortality 0.6%). The researchers conclude that novel MTA therapy in the phase I setting is associated with a "moderate risk" of toxicity, although most toxicities were "easily managed with dose interruption/reduction".
1
among patients with lymphocytes count of < 700/mm3 (OR 1.84; 95% CI 1.17, 2.90) and platelets count of < 400 000/mm3 (1.66; 1.09, 2.52).
Refine safety with OLED A new phase I trial concept, the PARASOL trial has been developed by a team of researchers from France.5 The trial uses a novel endpoint: the Optimal Long Exposure Dose (OLED), which aims to reinforce the safety and feasibility of targeted therapy combination regimens. The OLED represents the dose level, less than or equal to the MTD, where ≤ 2/7–8 or ≤ 3/9 patients experience definitive treatment discontinuations of any cause – except disease progression – between 4 and 24 weeks of treatment. 1. Postel-Vinay S, et al. Phase I trials of novel molecularly targeted therapies: Should we pay more attention to toxicities occurring after cycle 1? 46th Annual Meeting of the American Society of Clinical Oncology : abstr. 2515, 4 Jun 2010. Available from: URL: http://www.asco.org. 2. Alam SM, et al. Defining the risk of toxicity in phase I oncology trials of novel molecularly targeted agents: A single-center experience. 46th Annual Meeting of the American Society of Clinical Oncology : abstr. 2519, 4 Jun 2010. Available from: URL: http://www.asco.org. 3. Iasonos A, et al. Impact of miscoding dose-limiting toxicities in dose-escalation phase I studies. 46th Annual Meeting of the American Society of Clinical Oncology : abstr. e13007, 4 Jun 2010. Available from: URL: http:// www.asco.org. 4. Gomez-Roca CA, et al. An international pooled analysis identifying predictive factors associated with toxicities in phase I trials (Delphi). 46th Annual Meeting of the American Society of Clinical Oncology : abstr. 2517, 4 Jun 2010. Available from: URL: http://www.asco.org. 5. Neg
Data Loading...
