Concurrent chemoradiation for stage III, IVA and IVB cancer

Cisplatin + RT
Cisplatin (CDDP) 100 mg/m2 iv d1, 22 and 43
Concurrent radiotherapy 2 Gy/d to a total of 70 Gy

Forastiere AA et al. Concurrent chemotherapy and radiotherapy for organ preservation in advanced laryngeal cancer. N Engl J Med 2003; 349:2091 (link to the article).

Adelstein DJ et al. An intergroup phase III comparison of standard radiation therapy and two schedules of concurrent chemoradiotherapy in patients with unresectable squamous cell head and neck cancer. J Clin Oncol 2003; 21:92 (link to the article).

5-FU + Cisplatin + RT
Cisplatin (CDDP) 20 mg/m2/d civi d1-4 and 22-25
5-FU 1000 mg/m2/d civi d1-4 and 22-25
Concurrent radiotherapy 2 Gy/d to a total of 70 Gy

Adelstein DJ et al. Mature results of a phase III ranadomized trial comparing concurrent chemoradiotherapy with radiation therapy alone in patients with stage III and IV squamous cell carcinoma of the head and neck. Cancer 2000; 88:876 (link to the article).

5-FU + Carboplatin + RT
Carboplatin (Paraplatin) 70 mg/m2/d iv d1-4, 22-25 and 43-46
5-FU 600 mg/m2/d civi d1-4, 22-25 and 43-46
Concurrent radiotherapy 2 Gy/d to a total of 70 Gy

Calais G et al. Randomized trial of radiation therapy versus concomitant chemotherapy and radiation therapy for advanced stage oropharynx carcinoma. J Natl Cancer Inst 1999; 15:2081 (link to the article).

5-FU + RT
5-FU 1200 mg/m2/d civi d1-3 and 22-24
Concurrent radiotherapy 2 Gy/d to a total of 66 Gy

Browman GP et al. Placebo-controlled randomized trial of infusional flouruoracil during radiotherapy in locally advanced head and neck cancer. J Clin Oncol 1994; 12:2648 (link to the article).

Concurrent targeted-radiation therapy for stage III, IVA and IVB cancer (back to top)

Cetuximab + RT
Cetuximab (Erbitux) loading dose 400 mg/m2 iv, 1 week before XRT, then 250 mg/m2 iv qw
Concurrent radiotherapy 2 Gy/d to a total of 70 Gy

Approved by FDA on 3/1/2006 

Bonner JA et al. Radiotherapy plus cetuximab for squamous cell carcinoma of the head and neck. N Engl J Med 2006; 354:567 (link to the article).

Neoadjuvant chemotherapy followed by chemoradiation or radiation for stage III, IVA and IVB cancer (back to top)

TPF→ Carboplatin + RT
Docetaxel (Taxotere) 75 mg/m2 iv over 1 hour d1
Cisplatin (CDDP) 100 mg/m2 iv over 30 min-3 hours d1
5-FU 1000 mg/m2/d civi d1-4
Q3w x 3 cycles
3-8 weeks later:
Carboplatin (Paraplatin) AUC 1.5 iv over 1 hour qw x 7 weeks during RT
Concurrent radiotherapy 2 Gy/d to a total of 70-74 Gy
6-12 weeks later:
Surgical resection as needed

Approved by FDA on 9/28/07 (link to FDA file). 

Posner MR et al. Cisplatin and fluorouracil alone or with docetaxel in head and neck cancer. N Eng J Med 2007; 357:1705 (link to the article).

TPF→ RT
Docetaxel (Taxotere) 75 mg/m2 iv over 1 hour d1
Cisplatin (CDDP) 75 mg/m2 iv over 1 hour d1
5-FU 750 mg/m2/d civi d1-5
Q3w x 4 cycles
4-7 weeks later, radiotherapy 1.8-2 Gy/d to a total of 66-70 Gy or accelarated/hyperfractionated radiotherapy bid to a total of 70-74 Gy
Surgical resection as needed before or after radiotherapy

Approved by FDA on 10/17/06 (link to FDA site).

Vermorken JB et al. Cisplatin, fluorouracil, and docetaxel in unresectable head and neck cancer. N Eng J Med 2007; 357:1695 (link to the article).
 

Concurrent chemoradiation for stage III, IVA and IVB Nasopharyngeal cancer (back to top)

Cisplatin + RT → Cisplatin + 5-FU
Cisplatin (CDDP) 100 mg/m2 iv d1, 22 and 43
Concurrent radiotherapy 2 Gy/d to a total of 70 Gy
Followed by
Cisplatin (CDDP) 80 mg/m2 iv d1
5-FU 1000 mg/m2/d civi d1-4
Q4w x 3 cycles

Al-Sarraf, M et al. Chemoradiotherapy versus radiotherapy in patients with advanced nasopharyngeal cancer: Phase III randomized intergroup study 0099. J Clin Oncol 1998; 16:1310 (link to the article).

Oxaliplatin + RT
Oxaliplatin (Eloxatin) 70 mg/m2 iv over 2 hours qw x 6
Concurrent radiotherapy 2 Gy/d to a total of 70-74 Gy

Zhang L et al. Phase III study comparing standard radiotherapy with or without weekly oxaliplatin in treatment of locoregionally advanced nasopharyngeal carcinoma: preliminary results. J Clin Oncol 2005; 23:8461 (link to the article).
 

Chemotherapy for stage IVC (metastatic) cancer (back to top)

5-FU + Cisplatin + Bleomycin
Cisplatin (CDDP) 100 mg/m2 iv d1
5-FU 650 mg/m2/d civi d1-5
Bleomycin 15 mg iv d1 followed by 16 mg/m2/d civi d1-5
Q4w x 3 cycles

Boussen, H et al. Chemotherapy of metastatic and/or recurrent undifferentiated nasopharyngeal carcinoma with cisplatin, bleomycin, and fluorouracil. J Clin Oncol 1991; 9:1675 (link to the article).

5-FU + Cisplatin + Bleomycin + Epirubicin
Bleomycin 10 mg iv bolus on d1 followed by 12 mg/m2/d civi d1-4 in first 3 cycles only
5-FU 700 mg/m2/d civi d1-4
Epirubicin 70 mg/m2 iv d1
Cisplatin (CDDP) 100 mg/m2 iv d5
Q3w x 6 cycles

Taamma, A et al. Phase II trial of chemotherapy with 5-fluorouracil, bleomycin, epirubicin, and cisplatin for patients with locally advanced, metastatic, or recurrent undifferentiated carcinoma of the nasopharyngeal type. Cancer 1999; 86:1101 (link to the article).

5-FU + Cisplatin + Epirubicin + Mitomycin
5-FU 800 mg/m2/d civi d1-4
Epirubicin 70 mg/m2 iv d1
Mitomycin 10 mg/m2 iv d1 in cycle 1, 3 and 5 only
Cisplatin (CDDP) 100 mg/m2 iv d1
Q4w x 6 cycles

Hasbini, A et al. Phase II trial combining mitomycin with 5-fluorouracil, epirubicin, and cisplatin in recurrent and metastatic undifferentiated carcinoma of nasopharyngeal type. Ann Oncol 1999; 10:421 (link to the article).

Cisplatin + Gemcitabine
Cisplatin (CDDP) 50 mg/m2 iv d1 and 8
Gemcitabine (Gemzar) 1000 mg/m2 iv d1, 8 and 15
Q4w x 6 cycles

Ngan, RK et al. Combination gemcitabine and cisplatin chemotherapy for metastatic or recurrent nasopharyngeal carcinoma: report of a phase II study. Ann Oncol 2002; 13:1252 (link to the article).

5-FU + Cisplatin
Cisplatin (CDDP) 100 mg/m2 iv d1
5-FU 1000 mg/m2/d civi d1-4
Q3w

Forastiere AA et al. Randomized comparison of cisplatin plus fluorouracil and carboplatin plus fluorouracil versus methotrexate in advanced squamous-cell carcinoma of the head and neck. J Clin Oncol 1992; 10:1245 (link to the article).

5-FU + Carboplatin
Carboplatin (Paraplatin) 300 mg/m2 iv d1
5-FU 1000 mg/m2/d civi d1-4
Q4w

Forastiere AA et al. Randomized comparison of cisplatin plus fluorouracil and carboplatin plus fluorouracil versus methotrexate in advanced squamous-cell carcinoma of the head and neck. J Clin Oncol 1992; 10:1245 (link to the article).

Methotrexate
Methotrexate (MTX) 40 mg/m2 iv
Qw

Forastiere AA et al. Randomized comparison of cisplatin plus fluorouracil and carboplatin plus fluorouracil versus methotrexate in advanced squamous-cell carcinoma of the head and neck. J Clin Oncol 1992; 10:1245 (link to the article).

5-FU + LV + Cisplatin
Cisplatin (CDDP) 100 mg/m2 iv d1
5-FU 800 mg/m2/d civi d1-5
Leucovorin 50 mg/m2 po q6h d1-5
Q4w

Vokes EE et al. Cisplatin, fluorouracil and high dose leucovorin for recurrent or metastatic head and neck cancer. J Clin Oncol 1988; 6:618 (link to the article).

Cisplatin + Capecitabine
Cisplatin (CDDP) 75 mg/m2 iv d1
Capecitabine (Xeloda) 1000 mg/m2 po bid x 2w
Q3w

Hitt R et al. Phase II trial of  cisplatin and capecitabine in patients with squamous cell carcinoma of the head and neck, and correlative study of angiogenic factors. Br J Cancer 2004; 91:2005 (link to the article).

Cisplatin + Paclitaxel
Cisplatin (CDDP) 75 mg/m2 iv
Paclitaxel (Taxol) 135 mg/m2 civi x 24 hrs
Q3w

Forastiere AA et al. Phase III comparison of high-dose paclitaxel + cisplatin + granulocyte colony stimulating factor versus low-dose paclitaxel + cisplatin in advanced head and neck cancer. J Clin Oncol 2001; 19:1088 (link to the article).

Carboplatin + Paclitaxel
Carboplatin (Paraplatin) AUC 6 iv
Paclitaxel (Taxol) 200 mg/m2 iv over 3 h
Q3w

Clark JI et al. Phase II evaluation of paclitaxel in combination with carboplatin in advanced head and neck carcinoma. Cancer 2001; 92:2334 (link to the article).

Cisplatin + Docetaxel
Cisplatin (CDDP) 75 mg/m2 iv
Docetaxel (Taxotere) 75 mg/m2 iv
Q3w

Glisson BS et al. Phase II trial of docetaxel and cisplatin combination chemotherapy in patients with squamous cell carcinoma of the head and neck. J Clin Oncol 2002; 20:1593 (link to the article).

Targeted therapy for recurrent and metastatic cancer (back to top)

Cetuximab 
Cetuximab (Erbitux) loading dose 400 mg/m2 iv over 2 hrs, followed by 250 mg/m2 iv over 1 hr qw

Vermorken JB et al. Open-label, uncontrolled, multicenter phase II study to evaluate the efficacy and toxicity of cetuximab as a single agent in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck who failed to response to platinum-based therapy. J Clin Oncol 2007; 25:2171 (link to the article).   

Cisplatin + Cetuximab
Cisplatin (CDDP) 75-100 mg/m2 iv d1 q3-4w
Cetuximab (Erbitux) loading dose 400 mg/m2 iv over 2 hrs d1, followed by 250 mg/m2 iv over 1 hr qw

Burtness B et al. Phase III randomized trial of cisplatin plus placebo compared with cisplatin plus cetuximab in metastatic/recurrent head and neck cancer: an Eastern Cooperative Oncology Group study. J Clin Oncol 2005; 23:8646 (link to the article).

Herbst RS et al. Phase II multicenter study of the epidermal growth factor receptor antibody cetuximab and cisplatin for recurrent and refractory squamous cell carcinoma of the head and neck. J Clin Oncol 2005; 23:5578 (link to the article).

Baselga J et al. Phase II multicenter study of the antiepidermal growth factor receptor monoclonal antibody cetuximab in combination with platinum-based chemotherapy in patients with platinum-refractory metastatic and/or recurrent squamous cell carcinoma of the head and neck. J Clin Oncol 2005; 23:5568 (link to the article).

Carboplatin + Cetuximab
Carboplatin (Paraplatin) AUC 5 iv q3w
Cetuximab (Erbitux) loading dose 400 mg/m2 iv over 2 hrs d1, followed by 250 mg/m2 iv over 1 hr qw

Chan AT et al. Multicenter, phase II study of cetuximab in combination with carboplatin in patients with recurrent or metastatic nasopharyngeal carcinoma. J Clin Oncol 2005; 23:3568 (link to the article).

Baselga J et al. Phase II multicenter study of the antiepidermal growth factor receptor monoclonal antibody cetuximab in combination with platinum-based chemotherapy in patients with platinum-refractory metastatic and/or recurrent squamous cell carcinoma of the head and neck. J Clin Oncol 2005; 23:5568 (link to the article).

Paclitaxel + Cetuximab
Paclitaxel (Taxol) 80 mg/m2 iv qw
Cetuximab (Erbitux) loading dose 400 mg/m2 iv over 2 hrs d1, followed by 250 mg/m2 iv over 1 hr qw

Hitt R et al. Phase II study of combination cetuximab and weekly paclitaxel in patients with metastatic/recurrent squamous cell carcinoma of head and neck (SCCHN): Spanish Head and Neck Cancer Group (TTCC). 2007 ASCO annual meeting. Abstract 6012 (link to the abstract).

5-FU + Cisplatin + Cetuximab
Cisplatin (CDDP) 100 mg/m2 iv over 1 hour d1q3w x 6 cycles
5-FU 1000 mg/m2/d civi d1-4 q3w x 6 cycles
Cetuximab (Erbitux) loading dose 400 mg/m2 iv over 2 hours d1, followed by 250 mg/m2 iv over 1 hour ending at least 1 hour before chemotherapy qw until disease progression or unacceptable toxicity

Vermorken JB et al. Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Eng J Med 2008; 359:1116 (link to the article).

5-FU + Carboplatin + Cetuximab
Carboplatin (Paraplatin) AUC 5 iv over 1 hour d1q3w x 6 cycles
5-FU 1000 mg/m2/d civi d1-4 q3w x 6 cycles
Cetuximab (Erbitux) loading dose 400 mg/m2 iv over 2 hours d1, followed by 250 mg/m2 iv over 1 hour ending at least 1 hour before chemotherapy qw until disease progression or unacceptable toxicity

Vermorken JB et al. Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Eng J Med 2008; 359:1116 (link to the article). 

Cisplatin + Erlotinib
Erlotinib (Tarceva) 100 mg po qd to start 7 days before cisplatin until disease progression
Cisplatin (CDDP) 75 mg/m2 iv q3w x 6 cycles

Siu L et al. Phase I/II trial of erlotinib and cisplatin in patients with recurrent or metastatic squamous cell carcinoma of the head and neck: a Princess Margaret Hospital Phase II Consortium and National Cancer Institute of Canada Clinical Trials Group Study. J Clin Oncol 2007; 25: 2178 (link to the article).  

Cisplatin + Docetaxel + Erlotinib
Cisplatin (CDDP) 75 mg/m2 iv d1 q3w x 6 cycles
Docetaxel (Taxotere) 75 mg/m2 iv d1 q3w x 6 cycles
Erlotinib (Tarceva) 150 mg po qd until disease progression
Filgrastim (Neupogen) support

Kim ES et al.  Final results of a phase II study of erlotinib, docetaxel and cisplatin in patients with recurrent/metastatic head and neck cancer. 2007 ASCO annual meeting. Abstract 6013 (link to the abstract).