Tatalaksana Recurrent Nasopharyngeal Carcinoma

1. Penatalaksanaan
Recurrent Nasopharyngeal Carcinoma
Ferdy Ferdian, dr
Subdivisi Hemato Onkologi FK UNPAD
2013

2. Recurrent Nasopharyngeal Carcinoma
TATALAKSANA
RADIOTERAPI
External radioterapi
Brachiterapi
OPERASI
Nasofaringektomi per endoskopi
KEMOTERAPI
Single agent
Combination
Targeted theraphy COMBINATION

3. Recurrent Nasopharyngeal Carcinoma
RADIOTERAPI
• Options for the treatment for locoregional recurrence
of nasopharyngeal carcinoma include reirradiation or
nasopharyngectomy
• External beam radiation therapy (EBRT)
– Three-dimensional conformal radiation therapy (3D-CRT)
– Intensity-modulated radiation therapy (IMRT)
– Stereotactic radiosurgery
• Brachytherapy
– Internal radiation
Uptodate 2013, Treatment of recurrent and metastatic nasopharyngeal carcinoma

4. Recurrent Nasopharyngeal Carcinoma

5. Recurrent Nasopharyngeal Carcinoma
RADIOTERAPI
• Wu et al. Outcome of fractionated stereotactic
radiotherapy for 90 patients with locally
persistent and recurrent nasopharyngeal
carcinoma. Complete response rate after FSRT
was 66%.
Wu et al. Int J Radiat Oncol Biol Phys. 2007 Nov 1;69(3):761-9

6. Recurrent Nasopharyngeal Carcinoma
OPERASI
• Nasopharyngectomy is an option for patients
with small local recurrences and no distant
metastases
Uptodate 2013, Treatment of recurrent and metastatic nasopharyngeal carcinoma

7. Recurrent Nasopharyngeal Carcinoma

8. Recurrent Nasopharyngeal Carcinoma
OPERASI
• Chang et al. Salvage surgery for locally
recurrent nasopharyngeal carcinoma-A 10-
year experience. (N=38). The actual 3-year
survival and local control rate was 60% and
72.8%, respectively
Chang et al. Otolaryngol Head Neck Surg. 2004;131(4):497

9. Recurrent Nasopharyngeal Carcinoma
OPERASI
• Tao et al. Thirty-seven cases with recurrent
and residual lesions of NPC underwent salvage
surgery between March 1991 and January
2005 were analysed retrospectively. The 3-
and 5-year overall survival rates were 72.9%
and 51.3%, respectively
Tao et al. Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2011 Feb;46(2):108-13

10. Recurrent Nasopharyngeal Carcinoma
KEMOTERAPI
• Combination chemotheraphy
• Single agent chemotheraphy

11. Recurrent Nasopharyngeal Carcinoma
Combination chemotheraphy
• Observational data with combination
chemotherapy in recurrent or metastatic
nasopharyngeal carcinoma suggest that
platinum-containing regimens are most
effective in producing complete remission
Uptodate 2013, Treatment of recurrent and metastatic nasopharyngeal carcinoma

12. Recurrent Nasopharyngeal Carcinoma
Combination chemotheraphy
• Gebbia et al. cisplatin-based chemotherapy
could reach about 65% of tumor response in
recurrent NPC but the mean survival is only
about 11 months. These results might suggest
that the recurrent NPC be highly responsive to
chemotherapy but survival with chemotherapy
alone is poor
Suarez et al. Eur Arch Otorhinolaryngol. 2010 December; 267(12): 1811–1824

13. Recurrent Nasopharyngeal Carcinoma
Combination chemotheraphy
• Cisplatin 100 mg/m2 IV on D1 + 5-FU 1000 mg/m2/day by continuous IV
infusion on D1-4 every 3wk
• Cisplatin 75 mg/m2 IV on D1 + docetaxel 75 mg/m2 IV on D1 every 3wk
• Cisplatin 75 mg/m2 IV on D1 + paclitaxel 175 mg/m2 IV on D1 every 3wk
• Carboplatin AUC 6 IV on D1 + docetaxel 65 mg/m2 IV on D1 every 3wk
• Carboplatin AUC 6 IV on D1 + paclitaxel 200 mg/m2 IV on D1 every 3wk
• Cisplatin 50-70 mg/m2 IV on D1 + gemcitabine 1000 mg/m2 IV on
D1, 8, and 15 every 4wk
Stevenson et al. 2013. Nasopharyngeal Cancer Treatment Protocols
http://emedicine.medscape.com/article/2047748-overview

14. Recurrent Nasopharyngeal Carcinoma
Combination chemotheraphy
• Among the platinum-based doublets,
cisplatin plus 5-fluorouracil has been the
traditional first-line regiment
Uptodate 2013, Treatment of recurrent and metastatic nasopharyngeal carcinoma

15. Recurrent Nasopharyngeal Carcinoma
Combination chemotheraphy
• Kua et al. Carboplatin/5-fluorouracil as an
Alternative to Cisplatin/5- Fluorouracil for
Metastatic and Recurrent Head and Neck
Squamous Cell Carcinoma and Nasopharyngeal
Carcinoma. Carboplatin/5FU is not inferior to
cisplatin/5FU with regard to its efficacy.
However, there was a high rate of treatment-
related deaths with both regimens
Kua et al. Asian Pacific Journal of Cancer Prevention, Vol 14, 2013

16. Recurrent Nasopharyngeal Carcinoma
Combination chemotheraphy
• Ji et al. A prospective multicentre phase II
study of cisplatin and weekly docetaxel as
first-line treatment for recurrent or metastatic
nasopharyngeal cancer. N=47. 12.8% achieved
complete response. 57.4% showed partial
response. The 1-year survival rate was 89.9%.
Ji et al. Eur J Cancer. 2012 Nov;48(17):3198-204

17. Recurrent Nasopharyngeal Carcinoma
Combination chemotheraphy
• Chen et al. Triplet combination with
paclitaxel, cisplatin and 5-FU is effective in
metastatic and/or recurrent nasopharyngeal
carcinoma. N=95. The overall response and
disease control rates were 78.9 and 93.6
%, respectively. median overall survival were
22.7 months
Chen et al. Cancer Chemother Pharmacol. 2013 Feb;71(2):371-8

18. Recurrent Nasopharyngeal Carcinoma
Single agent chemotheraphy
• Single agents can be used if patients cannot
tolerate platinum-based agents
• Low performance status
Stevenson et al. 2013. Nasopharyngeal Cancer Treatment Protocols
http://emedicine.medscape.com/article/2047748-overview

19. Recurrent Nasopharyngeal Carcinoma
Single agent chemotheraphy
• Gemcitabine 1000 mg/m2 IV on D1, 8, and 15 every 4wk
• Gemcitabine 1250 mg/m2 IV on D1 and 8 every 3wk
• Methotrexate 40 mg/m2 IV weekly (3wk equals 1 cycle)
• Paclitaxel 200 mg/m2 IV every 3wk
• Docetaxel 75 mg/m2 IV every 3w
Stevenson et al. 2013. Nasopharyngeal Cancer Treatment Protocols
http://emedicine.medscape.com/article/2047748-overview

20. Recurrent Nasopharyngeal Carcinoma
Single agent chemotheraphy
• Approximate response rates to single
chemotherapeutic agents are as follows:
methotrexate, 31%; paclitaxel, 15% to
40%, depending on dose; docetaxel, 30% to
33%, depending on dose; gemcitabine, 13%
Lippincott William & Wilkin, Cancer Principles and practice of Oncology, 7th edition

21. Recurrent Nasopharyngeal Carcinoma
Targeted chemotheraphy
• Targeted therapy is a type of medication that blocks
the growth of cancer cells by interfering with specific
targeted molecules needed for carcinogenesis and
tumor growth, rather than by simply interfering with all
rapidly dividing cells (e.g. with traditional
chemotherapy)
• Targeted cancer therapies are expected to be more
effective than current treatments and less harmful to
normal cells

22. Recurrent Nasopharyngeal Carcinoma
Targeted chemotheraphy
• The main categories of targeted therapy are
small molecules and monoclonal antibodies
– Monoclonal antibody
• Cetuximab
– Small molecules
• Many are tyrosine-kinase inhibitors, ex erlotinib

23. Recurrent Nasopharyngeal Carcinoma

24. Recurrent Nasopharyngeal Carcinoma
Cetuximab
• A recombinant monoclonal antibody that blocks the
human epidermal growth factor receptor (EGFR) It
therefore inhibits the proliferation of cells that depend
on EGFR activation for growth
• Cetuximab is licensed for the treatment of patients
with squamous cell cancer of the head and neck in
combination with platinum-based chemotherapy for
recurrent and/or metastatic disease
NICE technology appraisal guidance, 2012
Cetuximab for the treatment of recurrent and/or metastatic squamous cell cancer of the head and neck

25. Recurrent Nasopharyngeal Carcinoma
Vermorken et al. n engl j med 359;11

26. Recurrent Nasopharyngeal Carcinoma
• Vermorken et al. Adding cetuximab to platinum-based
chemotherapy with fluorouracil significantly prolonged
the median overall survival from 7.4 months in the
chemotherapy-alone group to 10.1 months in the
group that received chemotherapy plus cetuximab
• The addition of cetuximab prolonged the median
progression-free survival time from 3.3 to 5.6
months
Vermorken et al. n engl j med 359;11

27. Recurrent Nasopharyngeal Carcinoma
• Reeves TD et al. Review the current state of the
data on the use of cetuximab in head and neck
squamous cell carcinoma
• Early evidence has shown cetuximab to be
effective in the treatment of HNSCC, and it should
be used to enhance, but not replace, current
treatment paradigms until further phase III data
are available.
Reeves TD et al. Otolaryngol Head Neck Surg. 2011 May;144(5):676-84

28. Recurrent Nasopharyngeal Carcinoma
• Yoshino T et al. n=33, Demonstrated efficacy and
safety of cetuximab in combination with cisplatin
and 5-fluorouracil for the first-line treatment of
Japanese patients with recurrent and/or
metastatic squamous cell carcinoma of the head
and neck justify the further use of this
combination treatment in this patient population
Yoshino T et al. Jpn J Clin Oncol. 2013 May;43(5):524-31

29. Recurrent Nasopharyngeal Carcinoma
• Hitt et al. Combination of cetuximab and weekly
paclitaxel in the first-line treatment of patients with
recurrent and/or metastatic squamous cell carcinoma
of head and neck. n=46
• The overall response rate was 54%
• complete responses and a disease control rate of 80%.
• Median progression-free and overall survival times
were 4.2 and 8.1 months, respectively.
Hitt et al. Annals of Oncology 23: 1016–1022, 2012

30. Recurrent Nasopharyngeal Carcinoma
• Erlotinib
– Reversible tyrosine kinase
inhibitor, which acts on
the epidermal growth
factor receptor (EGFR)

31. Recurrent Nasopharyngeal Carcinoma
• Lilian L et al. Trial of Erlotinib and Cisplatin in Patients
With Recurrent or Metastatic Squamous Cell
Carcinoma of the Head and Neck. N=51
• The intention-to-treat response rate was 21%, with one
complete and eight partial responses
• Disease stabilization was achieved in 49% patients
• Median progression-free survival was 3.3 months and
median overall survival was 7.9 months
Lilian L et al. J Clin Oncol 25:2178-2183. 2007

32. Sekian