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Incidence & prevalence
국립암정보센터
Introduction
• Localized Disease
– Curative intent by either surgery or radiation therapy
• Locally or Regionally Advanced Disease
– Curative intent combined modality therapy
including surgery, radiation therapy, and chemotherapy
• Recurrent and/or Metastatic Disease
– Palliative intent by chemotherapy
Harrison’s Principles of Internal Medicine, 18e
Induction chemotherapy
• Induction (or neoadjuvant) chemotherapy for locally
advanced SCCHN has shown high overall responses rates
Revisiting induction chemotherapy for head and neck cancer
Oncology (Williston Park) 2005; 19: 759–-770
• Most studies : No survival benefit, but exception of two phase
III trials that utilized cisplatin plus 5-fluorouracil (5-FU) (PF)
J Natl Cancer Inst 2004; 96: 1714–-1717
Br J Cancer 2000; 83: 1594–-1598
• A EORTC study : Organ preservation in patients with cancer of
the hypopharynx found an OS benefit
Larynx preservation in pyriform sinus cancer
J Natl Cancer Inst 1996; 88: 890–-899
Gastric Cancer 2007;10: 1–11
TTF
OS
Severe toxic effects
TPF
PF
Fewer toxic deaths with TPF versus PF in the Tax 323 study
Induction with a docetaxel or paclitaxel triplet :
lower rates of severe thrombocytopenia
and mucositis compared with PF
 The toxicity profile for taxane-containing induction seems
therefore manageable
The superiority of a triplet as induction regimen,
with docetaxel or paclitaxel added to PF
Gastric Cancer 2007;10: 1–11
Randomized studies to validate the
induction therapy approach
• Conclusive results with induction therapy improving
clinical outcomes over contemporary CRT are still
needed to establish induction therapy as standard
treatment for locally advanced SCCHN
• Four phase III randomized trials, all with induction
TPF, are either completed or ongoing
TPF + CRT vs CRT
Targeted agents into induction therapy
Gastric Cancer 2007;10: 1–11
Clinical trials of other targeted therapies in induction
• Gefitinib
– Selective inhibitor of epidermal growth factor receptor’s tyrosine
kinase domain
– The survival results overlap with results reported with CRT alone
• Lapatinib
– A dual tyrosine kinase inhibitor which interrupts the HER2 growth
receptor pathway
– Unacceptable renal toxic effects
• Bevacizumab and Erlotinib
– A humanized monoclonal antibody that inhibits vascular endothelial
growth factor A
– A reversible tyrosine kinase inhibitor
Selecting patients for induction therapy
• Whichever induction strategy is used will not
compromise subsequent definitive therapy
• As more steps are added to the treatment plan, one
of the key concerns is maintaining optimal timing
and avoiding delays
– Protracted treatment courses with gaps before or during RT
administration are known to compromise efficacy
Int J Radiat Oncol Biol Phys 2002; 52: 929–-936
Which patients may be better candidates for induction
• Patients who are not likely to tolerate chemotherapy are not
good candidates for induction therapy
• The choice to use induction could be made based on extent of
anatomical involvement
– In an analysis of phase II clinical trials with or without induction preceding CRT,
the use of induction appeared to have reduced the risk for distant failure
– For patients receiving CRT alone, advanced nodal stage (N2c–-N3) predicted
risk for distant failure and was associated with worse OS
Ann Oncol 2004; 15: 1179–-1186
Molecular biomarkers
• Low expression levels of the marker B-tubulin II were
found to be associated with better OS and PFS
b-Tubulin-II expression strongly predicts outcome in patients receiving induction
chemotherapy for locally advanced squamous carcinoma of the head and neck
J Clin Oncol 2009 in press
• Low baseline levels of vascular endothelial growth
factor (VEGF) and interleukin (IL)-6 correlated with
higher likelihood for CR
Serum biomarkers as predictors of clinical outcome after cetuximab-based therapy in
patients with locally advanced SCCHN.
J Clin Oncol 2009;27(15s): 6035 Abstr
HPV?
• HPV is an independent prognostic factor in
patients with locally advanced SCCHN
– The effect of HPV on survival was primarily driven by a
marked reduction on the risk for locoregional failure in
patients with HPV-positive tumors
Summary
• Induction TPF in locally advanced SCCHN
– Considered a standard induction regimen
– platinum/taxane backbone vs 5-FU
• Targeted agents
– Cetuximab, Bevacizumab and Erlotinib
• Selecting patients?
– Use the response to induction therapy for patient selection
• Biomarker study
– The patients with HPV-negative SCCHN may be more suitable
regimen