Recurrent Nasopharyngeal Carcinoma

Penatalaksanaan Recurrent Nasopharyngeal Carcinoma

Ferdy Ferdian, drSubdivisi Hemato Onkologi FK UNPAD

2013

Recurrent Nasopharyngeal CarcinomaTATALAKSANA

RADIOTERAPIExternal radioterapiBrachiterapi

OPERASINasofaringektomi per endoskopi

KEMOTERAPISingle agent

CombinationTargeted theraphy COMBINATION

Recurrent Nasopharyngeal CarcinomaRADIOTERAPI

• 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 radiationUptodate 2013, Treatment of recurrent and metastatic nasopharyngeal carcinoma

Recurrent Nasopharyngeal Carcinoma

Recurrent Nasopharyngeal CarcinomaRADIOTERAPI

• 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

Recurrent Nasopharyngeal CarcinomaOPERASI

• Nasopharyngectomy is an option for patients with small local recurrences and no distant metastases

Uptodate 2013, Treatment of recurrent and metastatic nasopharyngeal carcinoma



• 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


• 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

Recurrent Nasopharyngeal CarcinomaKEMOTERAPI

• Combination chemotheraphy• Single agent chemotheraphy

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



• 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 poorSuarez et al. Eur Arch Otorhinolaryngol. 2010 December; 267(12): 1811–1824

Recurrent Nasopharyngeal CarcinomaCombination 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 Protocolshttp://emedicine.medscape.com/article/2047748-overview


• Among the platinum-based doublets, cisplatin plus 5-fluorouracil has been the traditional first-line regiment



• 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


• 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


• 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

Recurrent Nasopharyngeal Carcinoma Single agent chemotheraphy

• Single agents can be used if patients cannot tolerate platinum-based agents

• Low performance status



• 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



• 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

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

Recurrent Nasopharyngeal CarcinomaTargeted 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


Recurrent Nasopharyngeal CarcinomaCetuximab

• 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, 2012Cetuximab for the treatment of recurrent and/or metastatic squamous cell cancer of the head and neck


Vermorken et al. n engl j med 359;11

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

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

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

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

Recurrent Nasopharyngeal Carcinoma• Erlotinib– Reversible tyrosine kinase

inhibitor, which acts on the epidermal growth factor receptor (EGFR)

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 monthsLilian L et al. J Clin Oncol 25:2178-2183. 2007

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Recurrent Nasopharyngeal Carcinoma