“Are There New Chemotherapy Drugs Behind the Corner?”

  • Valentina Gambardella
  • Noelia Tarazona
  • Marisol Huerta
  • Andres Cervantes


Up to now, the backbone of both adjuvant and palliative chemotherapy for colorectal cancer is still represented by 5-fluorouracil (5FU). However, we have currently several approved drugs with significant clinical activity in metastatic colon cancer. Apart from cytotoxics such as oxaliplatin, irinotecan, and fluoropyrimidines, we have antiangiogenics (bevacizumab, aflibercept, and ramucirumab), anti-epidermal growth factor receptor (EGFR), and tyrosine kinase inhibitors such as regorafenib. Despite remarkable prolongation of median survival, exceeding 24 months, most patients will be progressing over different lines of therapy, and there is a need and a role for new compounds to be added to our therapeutic armamentarium to improve efficacy [1].


  1. 1.
    Van Cutsem E, Cervantes A, Nordlinger B et al (2014) Metastatic colorectal cancer ESMO guideline. Ann Oncol 25(suppl 3):iii1–iii9CrossRefPubMedGoogle Scholar
  2. 2.
    Tanaka N, Sakamoto K, Okabe H et al (2014) Repeated oral dosing of TAS-102 confers high trifluridine incorporation into DNA and sustained antitumor activity in mouse models. Oncol Rep 32:2319–2326CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Mayer RJ, Van Cutsem E, Falcone A et al (2015) Randomized trial of TAS-102 for refractory metastatic colorectal cancer. N Engl J Med 372:1909–1919CrossRefPubMedGoogle Scholar
  4. 4.
    Koefoed K, Steinaa L, Søderberg JN, Kjær I, Jacobsen HJ, Meijer PJ et al (2011) Rational identification of an optimal antibody mixture for targeting the epidermal growth factor receptor. MAbs 3:584–595CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Dienstmann R, Patnaik A, Garcia-Carbonero R et al (2015) Safety and activity of the first-in-class Sym004 anti-EGFR antibody mixture in patients with refractory colorectal cancer. Cancer Discov 5:598–609CrossRefPubMedGoogle Scholar
  6. 6.
    Ciardiello F, Normanno N (2011) HER2 signaling and resistance to the anti-EGFR monoclonal antibody cetuximab: a further step toward personalized medicine for patients with colorectal cancer. Cancer Discov 1:472–474CrossRefPubMedGoogle Scholar
  7. 7.
    Siena S, Sartore-Bianchi A, Lonardi S et al (2015) Trastuzumab and lapatinib in HER2-amplified metastatic colorectal cancer patients (mCRC): the HERACLES trial. Presented at 2015 ASCO annual meeting. J Clin Oncol 33(suppl; abstr 3508)Google Scholar
  8. 8.
    The Cancer Genome Atlas Network (2012) Comprehensive molecular characterization of human colon and rectal cancer. Nature 487:330–337CrossRefPubMedCentralGoogle Scholar
  9. 9.
    Guinney J, Dienstmann R, Wang X et al (2015) The consensus molecular subtypes of colorectal cancer. Nat Med 21:1350–1356CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Taube JM, Klein A, Brahmer JR et al (2014) Association of PD-1, PD-1 ligands, and other features of the tumor immune microenvironment with response to anti-PD-1 therapy. Clin Cancer Res 20:5064–5074CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Le DT, Uram JN, Wang H et al (2015) PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med 372:2509–2520CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2018

Authors and Affiliations

  • Valentina Gambardella
    • 1
  • Noelia Tarazona
    • 1
  • Marisol Huerta
    • 1
  • Andres Cervantes
    • 1
  1. 1.Department of Medical OncologyBiomedical Research Institute INCLIVA, University of ValenciaValenciaSpain

Personalised recommendations