Voigt_relayout.qxp 6/7/09 16:14 Page 35
Advances in the Prognosis and Treatment of Medullary or Anaplastic Thyroid Cancer
chemotherapy.
24,26,31,34,41–43
More recent studies have evaluated pre- further molecular targeted therapies are currently being studied in
operative radiation or radiochemotherapy and increased the applied pre-clinical models. The most promising or advanced approaches are
radiation dose from <30Gy to hyperfractionated dose schedules with summarized in Table 1.
total doses between 45 and 60Gy.
1,39,40,44
Independent of the sequence
used for combined treatment, long-term survival occurred only in the Concluding Remarks
group of patients treated aggressively with radiation, chemotherapy Despite significant progress in decoding the molecular biology of thyroid
and surgery, achieving a complete local tumour resection.
1,26,31,35,39,40,45
cancer, the outcome of ATC is still dismal. Aggressive multimodal
Considering the fact that a complete tumour resection improves locoregional treatment reduces the rate of local relapse. However, due
overall survival, pre-operative radiation or radiochemotherapy might to the lack of active systemic treatment regimens, patients die of
be advantageous, since it may enhance operability.
39,40,45
Also in favor of metastatic disease. New molecular targeted agents are currently in early
pre-operative radiation or radiochemotherapy is the notion of Tennvall clinical evaluation, with partly promising results.
et al.
39
that a surgical biopsy or attempted resection might delay the
initiation of further local therapy due to poor wound healing. In MTC, no effective therapy existed for patients with unresectable
disease until recently. The identification of the RET proto-oncogene as
A randomized, prospective, multicenter clinical trial is necessary to finally the main driving force of MTC led to the introduction of targeted agents
clarify the question of the optimal sequence of multimodality treatment. in the treatment concept of MTC. Activity was proven in several phase
I/II clinical trials. The emerging therapies in thyroid cancer raise new
Molecular Targeted Therapy hopes, but their impact on clinical outcome needs to be further
New insights into molecular treatment options for ATC were mainly elucidated by well-designed randomized clinical trials. ■
derived from pre-clinical in vitro or in vivo studies. PPAR-γ is a
member of a superfamily of nuclear hormone receptors. High
Wieland Voigt, MD, is a Senior Physician in the Department
expression of PPAR-γ has recently been described in ATC cell lines.
46
of Internal Medicine at the Martin Luther University of
Treatment with PPAR-γ ligands led to the induction of apoptosis and Halle-Wittenberg. He participates in the preparation of the
downregulated the invasive potential of these cell lines.
46
Additional
German guidelines for the diagnosis and treatment of
thyroid cancer. He has authored or co-authored over 40
data suggested that PPAR-γ ligands may enhance etoposide-induced
manuscripts and book chapters in the field of cancer
apoptosis.
47
Based on these data, a phase I/II clinical study has been research and experimental therapeutics. Dr Voigt received
launched to evaluate the activity of a combination of paclitaxel and
specialist training at the University of Halle and completed
a training programme in molecular biology and
the oral PPAR-γ agonist CS7017. Several multikinase inhibitors have
experimental therapeutics at the Roswell Park Cancer Institute in Buffalo, New York.
been evaluated in clinical phase I/II studies in solid tumors. Some of He graduated from the Medical High School in Hanover.
them include patients with ATC. Axitinib, a receptor tyrosine kinase
Karin Jordan, MD, is a Physician in the Department of
inhibitor with particular activity against VEGF receptor,
1–3
PDGF-R beta
Hematology/Oncology at the Martin Luther University of
and KIT, induced a partial response in a patient with ATC.
48
Halle-Wittenberg. She is a member of several scientific
societies and is actively involved in the German study
group for oncology (AIO). Dr Jordan has authored or
Further studies currently recruiting investigate the activity of vascular
co-authored over 40 manuscripts and book chapters in
and growth factor targeting agents such as sorafenib, pazopanib, or the field of clinical oncology. She is principal investigator in
sunitinib in PDTC and ATC (for further information see clinicaltrials.gov
several studies in clinical oncology and is an Editorial
Assistant for the journal Onkologie. Dr Jordan received her
and Table 2 and Figure 1). Combretastatin A, an anti-endothelial agent
post-doctoral training in the Department of Oncology/Haematology under the
that exerted some activity in ATC as a single agent,
5
is currently being supervision of Department Director Professor Schmoll.
studied in ATC in combination with paclitaxel and carboplatin. Several
1. Are C, Shaha AR, Ann Surg Oncol, 2006;13:453–64. 20. Vitale G, et al., Cancer, 2001;91:1797–1808. 39. Tennvall J, et al., Acta Oncol, 1990;29:1025–8.
2. Wreesmann VB, Singh B, Surg Oncol Clin N Am, 2008;17:1–35, vii. 21. Lorenz K, et al., Surgery, 2005;138:986–93, discussion 993. 40. Besic N, et al., Eur J Surg Oncol, 2001;27:260–64.
3. Leboulleux S, et al., Clin Endocrinol (Oxf), 2004;61:299–310. 22. Mann K, et al., Onkologe, 2005;11:78–86. 41. Haigh PI, et al., Cancer, 2001;91:2335–42.
4. Schlumberger M, et al., Nat Clin Pract Endocrinol Metab, 23. Landis SH, et al., CA Cancer J Clin, 1998;48:6–29. 42. Junor EJ, et al., Eur J Surg Oncol, 1992;18:83–8.
2008;4:22–32. 24. Lo CY, et al., Am J Surg, 1999;177:337–9. 43. Schlumberger M, et al., Cancer, 1991;67:564–6.
5. Brown LR, Cohen EEW, Update Cancer Ther, 2008;3:1–11. 25. Venkatesh YS, et al., Cancer, 1990;66:321–30. 44. Kim JH, Leeper RD, Cancer, 1987;60:2372–5.
6. Wiseman SM, et al., Ann Surg Oncol, 2007;14:719–29. 26. Kihara M, et al., Surg Today, 2004;34:394–8. 45. Busnardo B, et al., J Endocrinol Invest, 2000;23:755–61.
7. Patel KN, Shaha AR, Cancer Control, 2006;13:119–28. 27. Gilliland FD, et al., Cancer, 1997;79:564–73. 46. Hayashi N, et al., Int J Oncol, 2004;24:89–95.
8. Costa AM, et al., Clin Endocrinol (Oxf), 2008;68:618–34. 28. Sugitani I, et al., World J Surg, 2001;25:617–22. 47. Kanbe E, et al., Exp Hematol, 2003;31:300–8.
9. Elliott DD, et al., Hum Pathol, 2008;39:15–20. 29. Giuffrida D, Gharib H, Ann Oncol, 2000;11:1083–9. 48. Kim S, et al., J Clin Oncol, 2006;24:5529.
10. Nikiforov YE, J Clin Endocrinol Metab, 2005;90:1243–5. 30. Veness MJ, et al., ANZ J Surg, 2004;74:559–62. 49. Kim S, et al., Clin Cancer Res, 2006;12:600–7.
11. Aiello A, et al., Endocrinology, 2006;147:4463–75. 31. De Crevoisier R, et al., Int J Radiat Oncol Biol Phys, 50. Harrington EA, et al., Nat Med, 2004;10:262–7.
12. Copland JA, et al., Oncogene, 2006;25:2304–17. 2004;60:1137–43. 51. Sorrentino R, et al., J Clin Endocrinol Metab, 2005;90:928–35.
13. Buolamwini JK, et al., Curr Cancer Drug Targets, 2005;5:57–68. 32. Ahuja S, Ernst H, J Endocrinol Invest, 1987;10:303–10. 52. Wang Z, et al., Clin Cancer Res, 2006;12:4755–65.
14. Koch CA, et al., BMC Cancer, 2006;6:131. 33. Shimaoka K, et al., Cancer, 1985;56:2155–60. 53. Kim S, et al., Mol Cancer Ther, 2005;4:632–40.
15. Bunone G, et al., Am J Pathol, 1999;155:1967–76. 34. Demeter JG, et al., Surgery, 1991;110:956–61, discussion 961–3. 54. Liu D, et al., J Clin Endocrinol Metab, 2007;92:4686–95.
16. Mitsiades CS, et al., J Clin Endocrinol Metab, 2006;91:4013–21. 35. Miccoli P, et al., Langenbecks Arch Surg, 2007;392:397–404. 55. Moretti F, et al., Oncogene, 1997;14:729–40.
17. Mitsiades CS, et al., Cancer Cell, 2004;5:221–30. 36. Ain KB, Semin Surg Oncol, 1999;16:64–9. 56. Kunnimalaiyaan M, et al., Surgery, 2006;140:1009–14,
18. Brandi ML, et al., J Clin Endocrinol Metab, 2001;86:5658–71. 37. Ain KB, et al., Thyroid, 2000;10:587–94. discussion 1014–15.
19. Brierley J, et al., Thyroid, 1996;6:305–10. 38. Tallroth E, et al., Cancer, 1987;60:1428–31.
US ONCOLOGY 35
Page 1  |  Page 2  |  Page 3  |  Page 4  |  Page 5  |  Page 6  |  Page 7  |  Page 8  |  Page 9  |  Page 10  |  Page 11  |  Page 12  |  Page 13  |  Page 14  |  Page 15  |  Page 16  |  Page 17  |  Page 18  |  Page 19  |  Page 20  |  Page 21  |  Page 22  |  Page 23  |  Page 24  |  Page 25  |  Page 26  |  Page 27  |  Page 28  |  Page 29  |  Page 30  |  Page 31  |  Page 32  |  Page 33  |  Page 34  |  Page 35  |  Page 36  |  Page 37  |  Page 38  |  Page 39  |  Page 40  |  Page 41  |  Page 42  |  Page 43  |  Page 44  |  Page 45  |  Page 46  |  Page 47  |  Page 48  |  Page 49  |  Page 50  |  Page 51  |  Page 52  |  Page 53  |  Page 54  |  Page 55  |  Page 56  |  Page 57  |  Page 58  |  Page 59  |  Page 60  |  Page 61  |  Page 62  |  Page 63  |  Page 64  |  Page 65  |  Page 66  |  Page 67  |  Page 68  |  Page 69  |  Page 70  |  Page 71  |  Page 72  |  Page 73  |  Page 74  |  Page 75  |  Page 76  |  Page 77  |  Page 78  |  Page 79  |  Page 80  |  Page 81  |  Page 82  |  Page 83  |  Page 84  |  Page 85  |  Page 86  |  Page 87  |  Page 88  |  Page 89  |  Page 90  |  Page 91  |  Page 92  |  Page 93  |  Page 94  |  Page 95  |  Page 96  |  Page 97  |  Page 98  |  Page 99  |  Page 100