Sorafenib tosylate in advanced kidney cancer: past, present and future.
The objective of this paper was to review the development of sorafenib tosylate in kidney cancer. The MedLine database, the Proceedings of the Annual American Society of Clinical Oncology meeting, as well as those of other key international meetings were extensively searched to identify relevant publications. Furthermore, the authors' direct experience with the drug was taken into account when commenting on the results retrieved. Sorafenib is a multikinase inhibitor that targets VEGF and PDGF receptors, other kinases, as well as the serine-threonine kinase Raf. Following early signs of activity from phase I and II studies, it has been shown to improve survival of pretreated advanced kidney cancer patients within a placebo-controlled, randomized, phase III trial, leading to its approval both in the United States and in Europe. Its activity has been subsequently confirmed in a real-world population by two expanded access programs performed globally, but not in a first-line setting; it also proved to be non-cross-resistant with two other molecularly targeted agents. Finally, its toxicity profile, which is acceptable and highly predictable, makes sorafenib appealing for combination treatments, especially with other molecularly targeted agents. Despite having been already demonstrated to be active in kidney cancer, the exact role of sorafenib in the first-line setting, in patients who have failed other molecularly targeted agents, and especially in combination with other agents, deserves further, prospective, studies.
Porta
Camillo
C
Medical Oncology and Laboratory of Pre-Clinical Oncology and Developmental Therapeutics, IRCCS San Matteo University Hospital, Piazzale C Golgi, Pavia, Italy. c.porta@smatteo.pv.it
Paglino
Chiara
C
Imarisio
Ilaria
I
Ferraris
Elisa
E
D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001557:Benzenesulfonates / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D018572:Disease-Free Survival; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011725:Pyridines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000077157:Sorafenib
D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D009536:Niacinamide; D000077157:Sorafenib