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Head and Neck Cancer


Figure 1: Global Health Status/Quality of Life Scores for Patients with Locally Advanced Head and Neck Cancer


100


10 20 30 40 50 60 70 80 90


0


–10 –20


Baseline Week 4 Month 4 Visit


Radiotherapy Month 8 Month 12 Radiotherapy + cetuximab Difference between treatment groups


From a randomised, phase III clinical trial at time-points during 12 months treatment with either radiotherapy and cetuximab or radiotherapy alone. The data plotted are least squares means estimates of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 global health status/quality of life (QoL) scores plotted as functions of treatment group and difference between treatment groups (bars = 95% confidence interval) at each time-point.


Reprinted with permission. © 2008 American Society of Clinical Oncology. All rights reserved. Curran D et al., 2007.48


additional quality-adjusted life-year. This suggested that cetuximab plus radiotherapy is cost-effective compared with radiotherapy alone using assumptions based on a cost-effectiveness threshold of £20,000 (approximately €24,000).50


Conclusions and Future Studies


Cetuximab is a significant advance in the treatment of LA SCCHN; its addition to radiotherapy confers significant benefits compared with radiotherapy alone. Based on the data from the Bonner phase III trial, the latest European Society for Medical Oncology (ESMO) guidelines recommend the use of cetuximab in combination with radiotherapy in LA SCCHN.51


The addition of cetuximab to


chemotherapy regimens may also improve efficacy both when cetuximab is included in induction therapy and when it is included in post-induction therapy regimens. Completed clinical trials have shown that there is generally little difference in adverse event frequencies when cetuximab is added to chemotherapy or chemoradiotherapy regimens. The most commonly reported side effect of cetuximab in the treatment of various malignancies is an acne-like skin rash; however, this rash can be managed and may correlate with a good response to therapy.31,52,53


Ongoing phase III


clinical studies will provide data on the efficacy and safety of the combination of cetuximab and concurrent chemoradiotherapy.


showing no difference between treatment groups for change from baseline to worst post-baseline scores were fatigue, nausea and vomiting, pain QLQ-C30, pain QLQ-H&N35, swallowing, sensory problems, speech problems, trouble with social eating, trouble with social contact and lower sexuality. The EORTC QLQ C30 global health status/QoL scores during the one-year follow-up period are plotted in Figure 1 and show the similarities in QoL status between the two treatment groups. The authors commented that the findings support the argument that adding cetuximab to radiotherapy is an attractive therapeutic option for patients with LA SCCHN.48


Cost-effectiveness


While the clinical evidence indicates a central role for the use of cetuximab in SCCHN, the cost of treatment needs to be assessed against the benefits. An analysis of the data from the Bonner phase III trial found that the additional cost per quality-adjusted life-year for patients receiving combined radiotherapy and cetuximab compared with radiotherapy alone was in the range of €7,538–10,836 and thus concluded that the combination of cetuximab and radiotherapy in SCCHN was cost-effective.49


Another analysis of this study indicated


that the incremental cost-effectiveness ratio of cetuximab plus radiotherapy compared with radiotherapy alone in LA SCCHN was £6,390 (approximately €7,668 at an exchange rate of €1.20 per £1) per


1. Gold KA, Lee HY, Kim ES, Targeted therapies in squamous cell carcinoma of the head and neck, Cancer, 2009;115: 922–35.


2. Leon X, Hitt R, Constenla M, et al., A retrospective analysis of the outcome of patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck refractory to a platinum-based chemotherapy, Clin Oncol (R Coll Radiol), 2005;17:418–24.


3. Cognetti DM, Weber RS, Lai SY, Head and neck cancer: an evolving treatment paradigm, Cancer, 2008;113:1911–32.


4. Specenier P, Vermorken JB, Targeted therapy in combination with chemotherapy in recurrent and/or metastatic head and neck cancer, Eur Oncol, 2010;6(1):43–6.


5. Eisbruch A, Commentary: induction chemotherapy for head 22


Another emerging aspect of SCCHN is that certain tumour types have been shown to have an aetiology involving human papillomavirus (HPV); oropharyngeal tumours, in particular, are more often HPV-positive than other head and neck neoplasms.54–57


oropharyngeal tumours are significantly more likely to respond to chemoradiotherapy than those with HPV-negative tumours58–61


Patients with HPV-positive and


this is also true of patients with tumours at other head and neck sites.62 The favourable prognosis of patients with HPV-positive SCCHN may mean that concurrent chemotherapy is too aggressive for such patients. Given the excellent efficacy and tolerability data for cetuximab plus radiotherapy in LA SCCHN,30,31


this combination may be a suitable


option for the treatment of HPV-positive SCCHN, although this would need to be investigated in appropriately designed clinical studies. The results of the clinical trials published to date raise several additional areas for future research, including the most effective ways of using cetuximab (sequential or simultaneous radiotherapy with chemotherapy) and the optimum choice of other chemotherapy agents to be combined with cetuximab. The data will help to determine which regimen is most effective in improving prognosis in terms of survival and disease progression, and which regimens reduce or eliminate permanent toxicity and safety concerns and those which negatively impact on QoL. Future research should attempt to identify biomarkers of response to EFGR-targeted therapies in SCCHN. Such studies, combined with ongoing clinical trials, should further improve the therapeutic benefits for patients with LA SCCHN and help target treatments. n


and neck cancer: hypothesis-based rather than evidence- based medicine, Oncologist, 2007;12:975–7.


6. Haddad R, Tishler RB, Norris CM, et al., Docetaxel, cisplatin, 5-fluorouracil (TPF)-based induction chemotherapy for head and neck cancer and the case for sequential, combined- modality treatment, Oncologist, 2003;8:35–44.


7. Haddad RI, Shin DM, Recent advances in head and neck cancer, N Engl J Med, 2008;359:1143–54.


8. Hitt R, Induction chemotherapy in head and neck cancer, Ann Oncol, 2006;17(Suppl. 10):x42–4.


9. Vermorken JB, Remenar E, van Herpen C, et al., Cisplatin, fluorouracil, and docetaxel in unresectable head and neck cancer, N Engl J Med, 2007;357:1695–704.


10. Knecht R, Radiotherapy, chemotherapy and target therapy


for treatment of head and neck cancer: new developments, HNO, 2009;57:436–45.


11. Culliney B, Birhan A, Young AV, et al., Management of locally advanced or unresectable head and neck cancer, Oncology (Williston Park), 2008;22:1152–61.


12. NCCN, Clinical practice guidelines in oncology – soft tissue sarcoma, National Comprehensive Cancer Network (NCCN), 2009;V.2.


13. Bernier J, Bentzen SM, Vermorken JB, Molecular therapy in head and neck oncology, Nat Rev Clin Oncol, 2009;6:266–77.


14. Le Tourneau C, Faivre S, Siu LL, Molecular targeted therapy of head and neck cancer: review and clinical development challenges, Eur J Cancer, 2007;43:2457–66.


15. Herbst RS, Langer CJ, Epidermal growth factor receptors as a


EUROPEAN ONCOLOGY & HAEMATOLOGY


Global health status/QoL score


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