Investigational New Drugs

, Volume 30, Issue 5, pp 2001–2007 | Cite as

Feasibility study of intra-patient sorafenib dose-escalation or re-escalation in patients with previously treated advanced solid tumors

  • Thomas J. Semrad
  • Courtney Eddings
  • Chong-Xian Pan
  • Derick H. Lau
  • David Gandara
  • Laurel Beckett
  • Primo N. LaraJr


Purpose To determine if intra-patient dose escalation of the multi-targeted kinase inhibitor sorafenib is feasible in patients with advanced pretreated solid malignancies. Methods An intra-patient dose escalation scheme starting at 400 mg BID was employed in this prospective trial. Doses were escalated to 600 mg BID for the second cycle and to 800 mg BID for the third cycle in the absence of grade 3+ adverse events. In the event of grade 3+ adverse events during cycle 1, doses were reduced to 400 mg daily through cycle 2. Dose re-escalation for cycle 3 was allowed in the absence of grade 3+ adverse events during cycle 2. Further dose escalation was prohibited. The primary endpoint was the overall percentage of patients tolerating dose escalation to 600 mg BID through cycle 2 or tolerating re-escalation to 400 mg BID through cycle 3. Results Fifty eligible patients with various solid tumors and a median of 3 prior therapies were enrolled. Eleven patients (22%) tolerated primary dose escalation or re-escalation. Only 14 patients (28%) completed cycle 1 without dose modification or discontinuing treatment. Seven of 13 patients tolerated primary dose escalation through cycle 2. Four of 5 patients tolerated dose re-escalation through cycle 3. Reasons for escalation failure included tumor progression (42%) and adverse events (26%). Common grade 3+ adverse events included hand-foot skin reaction, hypertension, and hypophosphatemia. Conclusions Intra-patient dose escalation and/or re-escalation of sorafenib were not feasible in pretreated solid tumor patients. Sorafenib dose escalation remains an investigational approach.


Dose escalation Dose re-escalation Dose-toxicity relationship Maximum tolerated dose Sorafenib 



Research support provided by Bayer Healthcare/Onyx Pharmaceuticals and UC Davis Cancer Center Support Grant, P30CA093373-06.

Study Identifier

NCT00810394. Presented in part at the 2010 ASCO Annual Meeting (Abstract #3055)


Dr. Lara received research funding from Bayer Healthcare and Onyx Pharmaceuticals for the conduct of this trial. There is no other conflict of interest disclosure.


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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Thomas J. Semrad
    • 1
    • 2
  • Courtney Eddings
    • 1
  • Chong-Xian Pan
    • 1
    • 2
  • Derick H. Lau
    • 1
    • 2
  • David Gandara
    • 1
  • Laurel Beckett
    • 3
  • Primo N. LaraJr
    • 1
    • 2
  1. 1.Division of Hematology/Oncology, Department of Internal MedicineUniversity of California Davis Cancer CenterSacramentoUSA
  2. 2.Section of Hematology/Oncology, The Department of Veterans Affairs Northern California Health Care SystemSacramentoUSA
  3. 3.Division of Biostatistics, Department of Public Health SciencesUniversity of California, DavisDavisUSA

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