TY - JOUR
T1 - Enhancing the clinical activity of sorafenib through dose escalation
T2 - Rationale and current experience
AU - Semrad, Thomas
AU - Gandara, David R
AU - Lara, Primo N
PY - 2011/3
Y1 - 2011/3
N2 - Sorafenib is an oral multitargeted tyrosine and serine/threonine kinase inhibitor approved for the treatment of advanced renal cell and hepatocellular carcinoma. An understanding of its dose-toxicity relationship has paved the way for trials seeking to enhance its clinical activity through the exploration of alternative dosing strategies. In this article, we review the dose-toxicity relationship of sorafenib observed during its phase I and early phase II testing, explore its toxicity profile at the recommended dose and schedule, discuss the evidence for dose escalation to higher levels, and examine the preliminary evidence for clinical activity of this strategy. Owing to a temporal relationship between toxicity and dose, it may be possible in select patients to escalate sorafenib to doses beyond those currently employed. However, because of the potential for increased toxicity, sorafenib dose escalation should currently be performed only in the context of a clinical trial.
AB - Sorafenib is an oral multitargeted tyrosine and serine/threonine kinase inhibitor approved for the treatment of advanced renal cell and hepatocellular carcinoma. An understanding of its dose-toxicity relationship has paved the way for trials seeking to enhance its clinical activity through the exploration of alternative dosing strategies. In this article, we review the dose-toxicity relationship of sorafenib observed during its phase I and early phase II testing, explore its toxicity profile at the recommended dose and schedule, discuss the evidence for dose escalation to higher levels, and examine the preliminary evidence for clinical activity of this strategy. Owing to a temporal relationship between toxicity and dose, it may be possible in select patients to escalate sorafenib to doses beyond those currently employed. However, because of the potential for increased toxicity, sorafenib dose escalation should currently be performed only in the context of a clinical trial.
KW - Dose-response relationship
KW - Drug
KW - Maximum tolerated dose
KW - Sorafenib
KW - Toxicity
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U2 - 10.1177/1758834010396117
DO - 10.1177/1758834010396117
M3 - Article
C2 - 21789159
AN - SCOPUS:79952828428
VL - 3
SP - 95
EP - 100
JO - Therapeutic Advances in Medical Oncology
JF - Therapeutic Advances in Medical Oncology
SN - 1758-8340
IS - 2
ER -