Head and Neck Cancers Treatment Regimens

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HEAD AND NECK CANCER TREATMENT REGIMENS

Clinical Trials: The National Comprehensive Cancer Network (NCCN) recommends cancer patient participation in clinical trials as the gold standard for treatment.

Cancer therapy selection, dosing, administration, and the management of related adverse events can be a complex process that should be handled by an experienced healthcare team. Clinicians must choose and verify treatment options based on the individual patient; drug dose modifications and supportive care interventions should be administered accordingly. The cancer treatment regimens below may include both U.S. Food and Drug Administration-approved and unapproved indications/regimens. These regimens are only provided to supplement the latest treatment strategies.

These Guidelines are a work in progress that may be refined as often as new significant data becomes available. The NCCN Guidelines® are a consensus statement of its authors regarding their views of currently accepted approaches to treatment. Any clinician seeking to apply or consult any NCCN Guidelines® is expected to use independent medical judgment in the context of individual clinical circumstances to determine any patient's care or treatment. The NCCN makes no warranties of any kind whatsoever regarding their content, use, or application and disclaims any responsibility for their application or use in any way.

Principle of Systemic Therapy

• Systemic therapy should be individualpli>

• Cisplatin-based induction chemotherapy can be used, followed by radiation-based locoregional treatment (ie. sequential chemoradiotherapy). However, an improvement in overall survival with the incorporation of induction chemotherapy compared to proceeding directly to state-of-the-art concurrent chemoradiotherapy (cisplatin preferred, category 1) has not been established in randomized studies.

• Cisplatin-based induction chemotherapy followed by high-dose, every-3-week cisplatin chemoradiotherapy is not recommended due to toxicity concerns.2,3

• After induction chemotherapy, multiple options can be used for the radiation-based portion of therapy. Radiotherapy alone versus radiotherapy plus weekly carboplatin or cetuximab are among the options.

Squamous Cell Cancers1,a

Note: All recommendations are category 2A unless otherwise indicated.

Primary Systemic Therapy + Concurrent Radiotherapy1

REGIMEN

DOSING

High-dose cisplatin (preferred; Category 1)4,5

Days 1, 22, and 43: Cisplatin 100mg/m2 IV + concurrent radiotherapy 2Gy/day to a total of 70Gy.

Cetuximab (Category 1 for oropharynx, hypopharynx, or larynx; Category 2B for lip, oral cavity, ethmoid sinus, maxillary sinus, occult primary)6

Day 1: Cetuximab 400mg/m2 loading dose over 2 hours, 1 week before radiotherapy, plus

Day 7: Begin radiotherapy with 7 weekly infusions of cetuximab 250mg/m2.

Carboplatin + infusional 5-FU (Category 1)7,8

Days 1–4: 5-FU 600mg/m2/day as continuous IV infusion for 4 days + carboplatin 70mg/m2/day IV bolus.

Repeat every 3 weeks for 3 cycles (given concurrently with radiotherapy).

5-FU + hydroxyurea9

Day 1: Hydroxyurea 1,000mg orally every 12 hours (11 doses/cycle) + 5-FU 800mg/m2/day continuous IV infusion, plus radiotherapy: 70Gy, delivered in 35 fractions; 1 fraction delivered daily Monday–Friday.

Concurrent radiotherapy and chemotherapy every other week for total treatment duration of 13 weeks.

Cisplatin + paclitaxel9

Day 1: Paclitaxel 30mg/m2 IV (every Monday), plus

Day 2: Cisplatin 20mg/m2 IV (every Tuesday). Repeat cycle every week for 7 cycles, plus radiotherapy: 70Gy, delivered in 35 fractions; 1 fraction delivered daily Monday–Friday.

Cisplatin + infusional 5-FU10

Day 1: Cisplatin 60mg/m2 over 15 minutes; plus

Days 1–5: 5-FU 800mg/m2/day by continuous infusion for 5 days; plus

Days 1–5: Radiotherapy: 2Gy repeated every other week for 7 cycles.

Carboplatin + paclitaxel (Category 2B)11

Day 1: Paclitaxel 40–45mg/m2/week and carboplatin 100mg/m2/week; prior to radiotherapy: 70.2Gy at 1.8Gy/fraction/day for 5 days/week.

Weekly cisplatin (Category 2B)12,13

Day 1–28: Cisplatin 40mg/mg2 IV over 30 minutes weekly; plus

Days 1–38: Radiotherapy (5 fractions/week): 1.8Gy single dose (up to total dose of 50.4Gy); plus

Days 22–38: Boost radiotherapy: 1.5Gy/day (up to 19.5Gy) in addition to regular dose. Booster doses to be given at least 6-hours after regular dose (total tumor dose of 69.9Gy).

OR

Day 1–28: Cisplatin 40mg/mg2 IV weekly; plus

Days 1–40: Radiotherapy: five fractions of 1.8Gy/week (up to total dose of 54Gy); plus Days 25–40: Boost radiotherapy: 1.5Gy/day (up to 19.5Gy) in addition to regular dose. Booster doses to be given at least 6-hours after regular dose.

Primary Chemotherapy With Postoperative Chemoradiation1

Cisplatin (Category 1 for high-risk non-oropharyngeal cancers)14–19

Days 1, 22, and 43: Cisplatin 100mg/m2 IV + radiotherapy.

Induction Chemotherapyb/Sequential chemotherapy1,c

Docetaxel + cisplatin + 5-FU (Category 1 if induction is chosen)24-26

Day 1: Docetaxel 75mg/m2 IV + cisplatin 75mg/m2 IV, plus

Days 1–5: 5-FU 750mg/m2/day continuous IV infusion for 5 days.

Repeat every 3 weeks for up to 4 cycles.

Paclitaxel + cisplatin+ infusional 5-FU27,d

Day 1: Paclitaxel 175mg/m2 over 3 hours

Day 2: Cisplatin 100mg/m2; plus

Day 2–6: 5-FU 500mg/m2/day continuous IV infusion for 5 days.

Repeat every 3 weeks for 3 cycles.

Nasopharynx Cancer1

Chemoradiation Followed by Adjuvant Chemotherapy1

Cisplatin + radiotherapy + cisplatin + 5-FU20,21

Cycles 1–3

Day 1: Cisplatin 100mg/m2 IV; plus radiotherapy.

Repeat cycle every 3 weeks; followed by

Cycles 4–6

Days 1: Cisplatin 80mg/m2 IV over 1 hour plus

Days 1-4: 5-FU 1,000mg/m2 continuous IV infusion daily.

Repeat cycle every 4 weeks for 3 cycles.

Carboplatin + radiotherapy + carboplatin + 5-FU (Category 2B)22

Cycles 1–3

Day 1: Carboplatin AUC 6mg·min/mL IV over 1 hour; plus radiotherapy: 200cGy/fraction with 5 daily fractions/week (to a total dose of 6600–7000cGy).

Repeat cycle every 3 weeks for 3 cycles; followed by

Cycles 4–6

Day 1: Carboplatin AUC 5mg·min/mL IV over 1 hour

Days 1–4: 5-FU 1,000mg/m2/day continuous IV infusion over 24 hours

Repeat cycle every 3 weeks for 2 cycles.

Cisplatin + radiotherapy without adjuvant chemotherapy (Category 2B)23

Cisplatin 40mg/m2 weekly for up to 7 weeks, concurrently with radiotherapy at a dose of 2.0 to 2.27Gy per fraction with 5 daily fractions per week for 6 to 7 weeks to a total dose of 66Gy or greater to the primary tumor and 60 to 66Gy to the involved neck area.

Induction Chemotherapyb/Sequential Chemotherapy1,e

Docetaxel + cisplatin + 5-FU (Category 1 if induction is chosen)30

Day 1: Docetaxel 70mg/m2 IV over 1 hour and cisplatin 75mg/m2 IV over 3 hours; followed by

Days 1–4: 5-FU 1,000mg/m2/day continuous IV infusion for 4 days.

Repeat every week for 3 cycles; followed by

Cisplatin 100mg/m2; plus radiotherapy: 5 daily fractions of 1.8 or 2Gy/day (total dose of 68.4Gy)

Repeat every 3 weeks.

Docetaxel + cisplatin

(Category 2B)31

Day 1: Docetaxel 75mg/m2 IV + cisplatin 75mg/m2 IV every 3 weeks for two cycles, followed by

Cisplatin 40mg/m2 IV weekly concurrent with radiotherapy.

Cisplatin + 5-FU25

Day 1: Cisplatin 100mg/m2/day IV.

Days 1–4: 5-FU 1,000mg/m2/day continuous IV infusion for 4 days.

Repeat cycle every 3 weeks for a minimum of 6 cycles.

Cisplatin + epirubicin + paclitaxel1

This regimen was included in the NCCN guidelines but no reference was provided to indicate appropriate dosage.

Following induction, agents to be used with concurrent chemoradiation typically include weekly cisplatin or carboplatin.22,50

Principles of Systemic Therapy1

• The choice of systemic therapy should be individualized based on patient characteristics (performance status, goals of therapy).

• Unless otherwise specified, regimens listed below can be used for either nasopharyngeal or non-nasopharyngeal cancer.

First-line Combination Therapy for Recurrent, Unresectable, or Metastatic Disease (With No Surgery or RT Option)1

Cisplatin or carboplatin + 5-FU + cetuximab (Category 1)31 (non-nasopharyngeal)

Day 1: Cisplatin 100mg/m2 IV or carboplatin AUC 5mg·min/mL 1 hour IV infusion, plus

Day 1: Cetuximab 400mg/m2 IV over 2 hours (initial dose), followed by

250mg/m2 IV over 1 hour once weekly

Days 1–4: 5-FU 1,000mg/m2/day continuous IV infusion for 4 days.

Repeat cycle every 3 weeks for a maximum of 6 cycles.

Cisplatin or carboplatin + docetaxel32

Day 1: Docetaxel 75mg/m2 IV over 1 hour; followed immediately by cisplatin 75mg/m2 IV.

OR

Day 1: Docetaxel 65mg/m2 IV over 1 hour; followed immediately by

carboplatin AUC 6mg·min/mL IV.

Repeat cycle every 3 weeks.

Cisplatin or carboplatin + paclitaxel33

Day 1: Cisplatin 75mg/m2/day IV + paclitaxel 175mg/m2 IV over 3 hours.

OR

Day 1: Carboplatin AUC 6mg·min/mL IV + paclitaxel 200mg/m2 IV over 3 hours.

Repeat cycle every 3 weeks for a minimum of 6 cycles.

Cisplatin + cetuximab34 (non-nasopharyngeal)

Day 1: Cetuximab 200mg/m2 IV over 120 minutes for 1 cycle, then cetuximab 125mg/m2/week IV over 60 minutes for subsequent cycles

Repeat once weekly, plus

Day 1: Cisplatin 100mg/m2 IV.

Repeat every 4 weeks.

Cisplatin + 5-FU33,35

Day 1: Cisplatin 100mg/m2/day IV

Days 1–4: 5-FU 1,000mg/m2/day continuous IV infusion for 4 days.

Repeat cycle every 3 weeks for a minimum of 6 cycles.

Cisplatin or carboplatin + docetaxel + cetuximab36 (non-nasopharyngeal)

Day 1: Cisplatin 75mg/m2 IV or carboplatin 5mg·min/mL IV

Day 1: Docetaxel 75mg/m2 IV + cetuximab (400mg/m2 on day 1 of cycle 1, then 250mg/m2 weekly).

Repeat cycle every 21 days for 4 cycles, followed by cetuximab 500mg/m2 IV every 2 weeks as maintenance therapy until disease progression or unacceptable toxicity.

Cisplatin or carboplatin + paclitaxel + cetuximab37,38 (non-nasopharyngeal)

Day 1: Cisplatin 75 or 100mg/m2 IV or carboplatin AUC 6mg·min/mL IV

Day 1: Paclitaxel 175mg/m2 IV.

Repeat every 3 weeks for 2 cycles, followed by

Day 1: Cisplatin 75 or 100mg/m2 IV or carboplatin AUC 6mg·min/mL every 3 weeks + cetuximab (400mg/m2 IV on day 1, then 250mg/m2 weekly) for 4 cycles.

Carboplatin + cetuximab42 (nasopharyngeal)

Day 1: Cetuximab initial dose of 400mg/m2 IV over 2 hours; followed by weekly doses of cetuximab 250mg/m2 IV over 1 hour; followed by carboplatin AUC 5mg·min/mL IV.

Repeat every 3 weeks for a maximum of 8 cycles.

Cisplatin + gemcitabine (Category 1)40,41 (nasopharyngeal)

Days 1 and 8: Gemcitabine 1,000mg/m2 IV

Days 1–3: Cisplatin 80mg/m2 IV in divided doses.

Repeat cycle every 3 weeks.

First-line Single Agents for Recurrent, Unresectable, or Metastatic Disease (With No Surgery or RT Option)1

Cisplatin34,43

Day 1: Cisplatin 100mg/m2 IV over 15–20 minutes.

Repeat every 3–4 weeks.

Carboplatin44

Day 1: 25mg/m2 daily followed by radiotherapy: 5 daily fractions of 1.8 or 2Gy.

Paclitaxel45

Day 1: Paclitaxel 80mg/m2 IV over 1 hour.

Repeat every 6 weeks.

Docetaxel46,47

Day 1: Docetaxel 40–100mg/m2 IV over 1 hour.

Repeat every 3 weeks.

5-FU43

Days 1–4: 5-FU 1,000mg/m2/day continuous IV infusion for 4 days.

Repeat every 3 weeks.

Methotrexate48,49

Day 1: Methotrexate 40mg/m2 IV weekly, with progressive increase to 60mg/m2, if tolerated.

Cetuximab50 (non-nasopharyngeal)

Day 1: Cetuximab 400mg/m2 over 2 hours as a loading dose (including a 20mg test dose); followed by cetuximab 250mg/m2 IV over 1 hour weekly.

Repeat for at least 6 weeks. If treatment response or stable disease, continue until progressive disease or unacceptable toxicity.

Gemcitabine51 (nasopharyngeal)

Days 1, 8, and 15: Gemcitabine 1,000mg/m2 IV over 30 minutes.

Repeat every 4 weeks.

Capecitabine52

Days 1–14: Capecitabine 1250mg/m2 orally twice daily; followed by a 1-week rest period.

Repeat every 3 weeks for at least two cycles.

Second-Line Therapy or Subsequent Therapy Options

Combination therapy options listed above.

Single-agent options listed above.

Afatinib (Category 2B)57,f (non-nasopharyngeal)

Day 1: Afatinib 40 mg orally daily until disease progression or unacceptable toxicity.

Pembrolizumab (Category 2B)54–56,f,g (non-nasopharyngeal; nasopharyngeal (Category 2B))

Day 1: Pembrolizumab 10mg/kg IV.

Repeat cycle every 2 weeks.

Nivolumab (Category 1)53,f (non-nasopharyngeal)

Day 1: Nivolumab 3mg/kg IV.

Repeat cycle every 2 weeks.

a Includes lip, oral cavity, oropharynx, hypopharynx, glottic larynx, supraglottic larynx, ethmoid sinus, maxillary sinus, occult primary.

b Induction chemotherapy should only be done in a tertiary setting.

c Following induction, agents to be used with concurrent chemoradiation typically include weekly carboplatin or cetuximab.48-50

d Patients with complete partial response of greater than 80% in primary tumor received additional chemoradiation therapy (ie, cisplatin 100mg/m2 on days 1, 22, and 43 plus 70Gy). Radiotherapy was administered in 35 fractions of 2Gy each over a 7-week period.

e Following induction, agents to be used with concurrent chemoradiation typically include weekly cisplatin22 or carboplatin.48

f Non-nasopharyngeal: if disease progression on or after platinum-containing chemotherapy.

g Nasopharyngeal: if previously treated, PD-L1-positive recurrent or metastatic disease.

References

  1. Referenced with permission from NCCN Clinical Practice Guidelines in Oncology™. Head and Neck Cancers. v1.2018. Available at:https://www.nccn.org/professionals/physician_gls/pdf/head-and-neck.pdf. Accessed April 4, 2018.

  2. Lefebvre JL, Pointreau Y, Rolland F, et al. Induction chemotherapy followed by either chemoradiotherapy or bioradiotherapy for larynx preservation: the TREMPLIN randomized phase II study. J Clin Oncol. 2013;31:853-859.

  3. Adelstein DJ, Moon J, Hanna E, et al. Docetaxel, cisplatin, and fluorouracil induction chemotherapy followed by accelerated fractionation/concomitant boost radiation and concurrent cisplatin in patients with advanced squamous cell head and neck cancer: A Southwest Oncology Group phase II trial (S0216). Head Neck. 2010;32:221-228.

  4. Forastiere AA, Zhang Q, Weber RS, et al. Long-term results of RTOG 91-11: a comparison of three nonsurgical treatment strategies to preserve the larynx in 4 patients with locally advanced larynx cancer. J Clin Oncol. 2013;31:845-852.

  5. Adelstein DJ, Li Y, Adams GL, 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(1):92-98.

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23. Chen L, Hu CS, Chen XZ, et al. Concurrent chemoradiotherapy plus adjuvant chemotherapy versus concurrent chemoradiotherapy alone in patients with locoregionally advanced nasopharyngeal carcinoma: a phase 3 multicentre randomised controlled trial. Lancet Oncol. 2012;13:163-171.

24. Vermorken JB, Remenar E, van Herpen C, et al; EORTC 24971/TAX 323 Study Group. Cisplatin, fluorouracil, and docetaxel in unresectable head and neck cancer. N Engl J Med. 2007;357(17):1695-1704.

25. Posner MR, Hershock DM, Blajman CR, et al. Cisplatin and fluorouracil alone or with docetaxel in head and neck cancer. N Engl J Med. 2007;357(17):1705-1715.

26. Pointreau Y, Garaud P, Chapet S, et al. Randomized trial of induction chemotherapy with cisplatin and 5-fluorouracil with or without docetaxel for larynx preservation. J Natl Cancer Inst. 2009;101:498-506.

27. Hitt R, López-Pousa A, Martínez-Trufero J, et al. Phase III study comparing cisplatin plus fluorouracil to paclitaxel, cisplatin, and fluorouracil induction chemotherapy followed by chemoradiotherapy in locally advanced head and neck cancer. J Clin Oncol. 2005;23:8636-8645.

28. Chitapanarux I, Lorvidhaya V, Kamnerdsupaphon P, et al. Chemoradiation comparing cisplatin versus carboplatin in locally advanced nasopharyngeal cancer: Randomised, non-inferiority, open trial. Eur J Cancer. 2007;43:1399-1406.

29. Haddad R, O'Neill A, Rabinowits G, et al. Induction chemotherapy followed by concurrent chemoradiotherapy (sequential chemoradiotherapy) versus concurrent chemoradiotherapy alone in locally advanced head and neck cancer (PARADIGM): a randomised phase 3 trial. Lancet Oncol. 2013;14:257-264.

30. Bae WK, Hwang JE, Shim HJ, et al. Phase II study of docetaxel, cisplatin and 5FU induction chemotherapy followed by chemoradiotherapy in locoregionally advanced npc. Cancer Chem other Pharmacol. 2010; 65:589-595.

31. Hui EP, Ma BB, Leung SF, et al. Randomized phase II trial of concurrent cisplatin-radiotherapy with or without neoadjuvant docetaxel and cisplatin in advanced nasopharyngeal carcinoma. J Clin Oncol. 2009;27:242-249.

32. Vermorken JB, Mesia R, Rivera F, et al. Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med. 2008;359:1116-1127.

33. Samlowski WE, Moon J, Kuebler JP, et al. Evaluation of the combination of docetaxel/carboplatin in patients with metastatic or recurrent squamous cell carcinoma of the head and neck (SCCHN): a Southwest Oncology Group Phase II study. Cancer Invest. 2007;25:182-188.

34. Gibson MK, Li Y, Murphy B, et al. Randomized phase III evaluation of cisplatin plus fluorouracil versus cisplatin plus paclitaxel in advanced head and neck cancer (E1395): An Intergroup Trial of the Eastern Cooperative Oncology Group. J Clin Oncol. 2005;23:3562-3567.

35. Burtness B, Goldwasser MA, Flood W, et al. Phase III randomized trial of cisplatin plus placebo versus cisplatin plus cetuximab in metastatic/recurrent head and neck cancer: An Eastern Cooperative Oncology Group Study. J Clin Oncol. 2005;23:8646-8654.

36. Forastiere AA, Metch B, Schuller DE, et al. Randomized comparison of cisplatin plus flurouracil and carboplatin plus fluorouracil versus methotrexate in advanced squamous cell carcinoma of the head and neck: A Southwest Oncology Group Study. J Clin Oncol. 1992;10:1245-1251.

37. Guigay J, Fayette J, Dillies A-F, et al. Cetuximab, docetaxel, and cisplatin (TPEx) as first-line treatment in patients with recurrent or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN): Final results of phase II trial GORTEC 2008-03 [abstract]. J Clin Oncol. 2012;30(Suppl 15):Abstract 5505.

38. Price KA, Cohen EE. Current treatment options for metastatic head and neck cancer. Curr Treat Options Oncol. 2012;13:35-46.

39. Herbst RS, Arquette M, Shin DM, 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;23:5578-5587.

40. Jin Y, Cai XY, Shi YX, et al. Comparison of five cisplatin-based regimens frequently used as the first-line protocols in metastatic nasopharyngeal carcinoma. J Cancer Res Clin Oncol. 2012 Oct;138(10):1717-25.

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42. Chan AT, Hsu MM, Goh BC, et al. Multicenter, phase II study of cetuximab in combination with carboplatin in patients with recurrent or metastatic nasopharyngeal carcinoma. J Clin Oncol. 2005;23:3568-3576.

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45. Grau JJ, Caballero M, Verger E, et al. Weekly paclitaxel for platin-resistant stage IV head and neck cancer patients. Acta Otolaryngol. 2009;129:1294-1299.

46. Catimel G, Verweij J, Mattijssen V, et al. Docetaxel (Taxotere): an active drug for the treatment of patients with advanced squamous cell carcinoma of the head and neck. EORTC Early Clinical Trials Group. Ann Oncol. 1994;5:533- 46537.

47. Guardiola E, Peyrade F, Chaigneau L, et al. Results of a randomised phase II study comparing docetaxel with methotrexate in patients with recurrent head and neck cancer. Eur J Cancer. 2004;40:2071-2076.

48. Stewart JS, Cohen EE, Licitra L, et al. Phase III study of gefitinib compared with intravenous methotrexate for recurrent squamous cell carcinoma of the head and neck [corrected]. J Clin Oncol. 2009;27:1864-1871.

49. Forastiere AA, Metch B, Schuller DE, et al. Randomized comparison of cisplatin plus fluorouracil and carboplatin plus fluorouracil versus methotrexate in advanced squamous-cell carcinoma of the head and neck: a Southwest Oncology Group study. J Clin Oncol. 1992;10:1245-1251.

50. Vermorken JB, Trigo J, Hitt R, 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 respond to platinum-based therapy. J Clin Oncol. 2007;25:2171-2177.

51. Zhang L, Zhang Y, Huang PY, et al. Phase II clinical study of gemcitabine in the treatment of patients with advanced nasopharyngeal carcinoma after the failure of platinum-based chemotherapy. Cancer Chemother Pharmacol. 2008;61:33-38.

52. Martinez-Trufero J, Isla D, Adansa JC, et al. Phase II study of capecitabine as palliative treatment for patients with recurrent and metastatic squamous head and neck cancer after previous platinum-based treatment. Br J Cancer. 2010;102:1687-1691.

53. Ferris R, Blumenschein G, Fayette J, et al. Nivolumab for recurrent squamous-cell carcinoma of the head and neck. N Engl J Med. 2016;375:1856-1867.

54. Seiwert TY, Burtness B, Mehra R, et al. Safety and clinical activity of pembrolizumab for treatment of recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-012): an open-label, multicentre, phase 1b trial. Lancet Oncol. 2016;17:956-965.

55. Chow LQ, Haddad R, Gupta S, et al. Antitumor activity of pembrolizumab in biomarker-unselected patients with recurrent and/or metastatic head and neck squamous cell carcinoma: results from the phase Ib KEYNOTE-012 expansion cohort. J Clin Oncol. 2016;34:3838-3845.

56. Hsu C, Lee SH, Ejadi S, et al. Safety and antitumor activity of pembrolizumab in patients with programmed death-ligand 1-positive nasopharyngeal carcinoma: results of the KEYNOTE-028 study. J Clin Oncol. 2017;35:4050-4056.

57. Machiels JP, 56 Haddad RI, Fayette J, et al. Afatinib versus methotrexate as second-line treatment in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck progressing on or after platinum-based therapy (LUX-Head & Neck 1): an open-label, randomised phase 3 trial. Lancet Oncol. 2015;16:583-594.

(Revised 4/2018)

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Head and Neck Cancer Drug Monographs

Head And Neck Cancers

BLEOMYCIN ERBITUX GLEOSTINE
HYDREA KEYTRUDA METHOTREXATE FOR INJECTION
METHOTREXATE INJECTION OPDIVO TAXOTERE
TREXALL

Data provided by the Monthly Prescribing Reference (MPR) Hematology/Oncology Edition.

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