Difference between revisions of "Regorafenib (Stivarga)"

Revision as of 21:32, 15 December 2015

General information

Class/mechanism: Small molecule inhibitor of multiple tyrosine kinases, such as: VEGFR1, VEGFR2, VEGFR3, KIT, RET, PDGFR-alpha, PDGFR-beta, FGFR1, FGFR2, TIE2, DDR2, Trk2A, Eph2A, RAF-1, BRAF, BRAFV600E, SAPK2, PTK5, and Abl, which are involved in tumor cell proliferation, survival, and angiogenesis. Its major active metabolites are M-2 and M-5.^[1]^[2]^[3]
Route: PO
Extravasation: n/a
Black Box Warning: Severe and sometimes fatal hepatotoxicity has been observed in clinical trials. Monitor hepatic function prior to and during treatment. Interrupt and then reduce or discontinue regorafenib for hepatotoxicity as manifested by elevated liver function tests (LFTs) or hepatocellular necrosis, depending upon severity and persistence.

For conciseness and simplicity, HemOnc.org currently will focus on treatment regimens and not list information such as: renal/hepatic dose adjustments, metabolism (including CYP450), excretion, monitoring parameters (although this will be considered for checklists), or manufacturer. Instead, for the most current information, please refer to your preferred pharmacopeias such as Micromedex, Lexicomp, UpToDate (courtesy of Lexicomp), or the package insert.

Diseases for which it is used

Patient drug information

History of changes in FDA indication

9/27/2012: FDA approved for "patients with metastatic colorectal cancer (mCRC) who have been previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, an anti-VEGF therapy, and, if KRAS wild type, an anti-EGFR therapy."
2/25/2013: FDA approved for "patients with advanced gastrointestinal stromal tumors (GIST) that cannot be surgically removed and no longer respond to other FDA-approved treatments for this disease."

Also known as

BAY 73-4506.

References

[insert-1] 1.0 ^1.1 Regorafenib (Stivarga) package insert

[2] Regorafenib (Stivarga) package insert (locally hosted backup)

[3] Stivarga manufacturer's website

[4] Regorafenib (Stivarga) patient drug information (Chemocare)

[5] Regorafenib (Stivarga) patient drug information (UpToDate)

[1]

[2]

[3]

[4]

[5]

@@ Line 1: / Line 1: @@
-'''FDA approved 9/27/2012.'''
 ==General information==
 Class/mechanism: Small molecule inhibitor of multiple tyrosine kinases, such as: VEGFR1, VEGFR2, VEGFR3, KIT, RET, PDGFR-alpha, PDGFR-beta, FGFR1, FGFR2, TIE2, DDR2, Trk2A, Eph2A, RAF-1, BRAF, BRAFV600E, SAPK2, PTK5, and Abl, which are involved in tumor cell proliferation, survival, and angiogenesis.  Its major active metabolites are M-2 and M-5.<ref name="insert">[http://labeling.bayerhealthcare.com/html/products/pi/Stivarga_PI.pdf Regorafenib (Stivarga) package insert]</ref><ref>[[Media:Regorafenib.pdf | Regorafenib (Stivarga) package insert (locally hosted backup)]]</ref><ref>[http://www.stivarga.com Stivarga manufacturer's website]</ref>
@@ Line 13: / Line 11: @@
 *[[Sarcoma|GIST (Gastrointestinal Stromal Tumor)]]
 *[[Renal cancer]]
-==Clinical trials==
-*CORRECT: A randomized, double-blind, placebo-controlled phase III study of regorafenib plus BSC versus placebo plus BSC in patients with metastatic colorectal cancer (CRC) who have progressed after standard therapy [http://www.asco.org/ASCOv2/Meetings/Abstracts?&vmview=abst_detail_view&confID=115&abstractID=87795 2012 ASCO Gastrointestinal Cancers Symposium abstract LBA385];<ref>Axel Grothey, Alberto F. Sobrero, Salvatore Siena, Alfredo Falcone, Marc Ychou, Heinz-Josef Lenz, Takayuki Yoshino, Frank Cihon, Andrea Wagner, Eric Van Cutsem, on behalf of the CORRECT Study Team. Results of a phase III randomized, double-blind, placebo-controlled, multicenter trial (CORRECT) of regorafenib plus best supportive care (BSC) versus placebo plus BSC in patients (pts) with metastatic colorectal cancer (mCRC) who have progressed after standard therapies. 2012 ASCO Gastrointestinal Cancers Symposium abstract LBA385 [http://www.asco.org/ASCOv2/Meetings/Abstracts?&vmview=abst_detail_view&confID=115&abstractID=87795 link to abstract]</ref> [http://clinicaltrials.gov/show/NCT01103323 Clinicaltrials.gov NCT01103323]; [http://healthcare.bayer.com/scripts/pages/en/research_development/clinical_trials/trial_finder/trialfinder_detail.php?trialid=14387 Bayer study 14387]
-*Regorafenib in Patients With Metastatic and/or Unresectable Gastrointestinal Stromal Tumor after  Failure with Imatinib or Sunitinib;<ref>George S, Wang Q, Heinrich MC, Corless CL, Zhu M, Butrynski JE, Morgan JA, Wagner AJ, Choy E, Tap WD, Yap JT, Van den Abbeele AD, Manola JB, Solomon SM, Fletcher JA, von Mehren M, Demetri GD. Efficacy and safety of regorafenib in patients with metastatic and/or unresectable GI stromal tumor after failure of imatinib and sunitinib: a multicenter phase II trial. J Clin Oncol. 2012 Jul 1;30(19):2401-7. Epub 2012 May 21. [http://jco.ascopubs.org/content/30/19/2401.long link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/22614970 PubMed]</ref> [http://clinicaltrials.gov/ct2/show/NCT01068769 Clinicaltrials.gov NCT01068769]
-*[http://www.cancer.gov/clinicaltrials/search/results?protocolsearchid=6566374 List of regorafenib clinical trials at Cancer.gov]
 ==Patient drug information==