There are now five different classes of drugs with significant antitumor activity in colon cancer:
Fluoropyrimidine (5-fluorouracil [5-FU] which is usually given with leucovorin [LV], capecitabine, tegafur plus uracil [UFT]). Irinotecan, Oxaliplatin, Cetuximab and panitumumab. The latter two are monoclonal antibodies (MoAbs) directed against the epidermal growth factor receptor (EGFR), and bevacizumab, is a monoclonal antibody targeting vascular endothelial growth factor (VEGF). Recently another antibody was approved for colon cancer - Zaltrap, as well as the drug Stivarga. The best way to combine and sequence all of these drugs to optimize treatment is not yet established, although for intial treatment of metasatic colorectal cancer NCCN recommends combinations of 5FU and Lekovorin with oxaliplatin or irinotecan with or without Avastin, CAPEOX, 5FU/Leukovorin, Xeloda and Avastin or Folfoxiri.
For second or third line therapy, single agents are acceptable but NCCN lists only irinotecan as a single agent. It also lists combinations of these drugs, Erbitux and Vectbix(for wild type KRA patients), see p. COL-C of the NCCN guideline for colon cancer. NCCN has a complex schema when to give what for second line and also lists Erbitux and Vectbix. However, capecitabine is also FDA approved as a single agent. NCCN does not list 5FU/Leikovorin but it can also be considered appropriate given the long history of its use for colorectal metastatic cancer and support from many older papers.
Recently, Stivarga was also approved. STIVARGA® (regorafenib) is indicated for the treatment of patients with metastatic colorectal cancer (CRC) 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.
NCCN, Colon cancer 2013
STIVARGA Prescribing Information. Wayne, NJ: Bayer HealthCare Pharmaceuticals Inc; 2013.
Grothey A, Sobrero A, Siena S, et al; 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 with metastatic colorectal cancer (mCRC) who have progressed after standard therapies. Poster presented at: American Society of Clinical Oncology 2012 Gastrointestinal Cancers Symposium; January 19-21, 2012; San Francisco, CA.
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