Association of CTCAE v4 grading of hypertension with toxicity in patients with renal cancer receiving vascular endothelial growth factor (VEGF)-targeting agents

Autor: Scott T. Tagawa, Irene Karpenko, David M. Nanus, Himisha Beltran, Naveed Akhtar, Beerinder Singh
Rok vydání: 2013
Předmět:
Zdroj: Journal of Clinical Oncology. 31:447-447
ISSN: 1527-7755
0732-183X
DOI: 10.1200/jco.2013.31.6_suppl.447
Popis: 447 Background: The NCI Common Terminology Criteria for Adverse Events (CTCAE) system underwent a change to version 4 in May 2009. In addition to system re-organization, several AE categories underwent changes in grading, including hypertension (HTN). As many anti-neoplastic agents, particularly those targeting VEGF are associated with HTN, changing in the grading system may result in changes to maximum tolerated or recommended phase II doses (MTD or RP2D) in dose-escalation studies using classic trial schemas (such as 3+3 design). Methods: We reviewed individual patient data of a phase I/II trial of sorafenib plus gemcitabine and capecitabine for advanced renal cell carcinoma (RCC). The phase I portion of the study was conducted to define the dose-limiting toxicity and RP2D of the combination (Am J Clin Oncol, 2011). The phase II portion further assessed efficacy as defined by objective response rate. Initial grading of AE’s during this study used CTCAE v3. Individual patient data was reviewed and HTN AE’s were re-graded using CTCAE v4 criteria for up to 12 cycles of therapy on study. Results: Of 28 pts enrolled, 23 (82.1%) had complete source documents available for the complete evaluation of HTN. The table compares each individual’s highest CTCAE v3 versus v4 grading of HTN on study. All pts had HTN AE’s using CTCAE v4. Only 1 pt maintained grading using both versions (Gr 3), with 22 (95.7%) changing grades. Two (8.7%) moved from Gr 0 to Gr 1, fourteen 60.9(%) from Gr 0 to Gr 2, four (17.4%) from Gr 1 to Gr 2, one from Gr 1 to Gr 3, and two (8.7%) from Gr 2 to Gr 3. Conclusions: Re-classification of grading in this study demonstrates that only 4.3% maintained stable grading of HTN across systems, with 65.2% increasing by 2 grades. The change in AE reporting criteria has the potential significantly impact results of clinical trials. This may be particularly important with VEGF-targeted agents, with emerging data pointing towards HTN as a pharmacodynamic marker in pts with RCC, and may affect dosing of other drugs with blood pressure effects, including CYP17 inhibitors for prostate cancer. Clinical trial information: NCT00121251. [Table: see text]
Databáze: OpenAIRE
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