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45 regimens on this page 86 variants on this page

Adjuvant chemotherapy & radiation therapy

Cisplatin & RT

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RT: Radiation Therapy

Regimen #1

Study	Evidence	Comparator	Efficacy
Cooper et al. 2004 (RTOG 9501, ECOG R9501, SWOG 9515)	Phase III	Radiation therapy	Seems to have superior DFS

Patients "had undergone macroscopically complete resection of disease" and at least one high-risk characteristic: "histologic evidence of invasion of two or more regional lymph nodes, extracapsular extension of nodal disease, and microscopically involved mucosal margins of resection."

Chemoradiotherapy

Cisplatin (Platinol) 100 mg/m² IV once per day on days 1, 22, 43
Concurrent radiation therapy, 2 Gy fractions x 30 fractions (total dose: 60 Gy), given 5 times per week over 6 weeks, with optional boost of 2 Gy fractions x 3 fractions (boost dose: 6 Gy) to high-risk sites

Supportive medications

Hydration before and after treatment
Antiemetics per physician choice
Optional use of feeding tubes

7-week course

Regimen #2

Study	Evidence	Comparator	Efficacy
Bernier et al. 2004 (EORTC 22931)	Phase III	Radiation therapy	Seems to have superior OS

Chemoradiotherapy

Cisplatin (Platinol) 100 mg/m² IV once per day on days 1, 22, 43
Concurrent radiation therapy, 2 Gy fractions x 27 fractions (total dose: 54 Gy), given 5 times per week over 5.5 weeks, with boost to areas at "high risk for malignant dissemination or that had inadequate resection margins" of 2 Gy fractions x 6 fractions (boost dose: 12 Gy)

Supportive medications

"Prophylactic hydration and antiemetic agents"

7-week course

Regimen #3

Study	Evidence	Comparator	Efficacy
Bachaud et al. 1991	Phase III	Radiation therapy	Superior OS

Chemoradiotherapy

Cisplatin (Platinol) 50 mg/m² IV bolus once per week on the first day of radiation
Concurrent radiation therapy, 1.7 Gy fractions x ~32 fractions (total dose: 54 Gy), given 5 times per week, with boost to "primary site and/or cervical lymph nodes" with 1.8 to 2 Gy fractions for an additional boost dose of 11 to 16 Gy to close (<5 mm) or positive margin areas of (overall dose to these sites: 65 to 70 Gy). A boost of 11 to 20 Gy was given to metastatic nodal sites (overall dose to these sites: 65 to 74 Gy); see Bachaud et al. 1996 for details.

Supportive medications

"Forced hydration" with Cisplatin (Platinol)

7 to 9-week course, depending on duration of radiation therapy

References

Bachaud JM, David JM, Boussin G, Daly N. Combined postoperative radiotherapy and weekly cisplatin infusion for locally advanced squamous cell carcinoma of the head and neck: preliminary report of a randomized trial. Int J Radiat Oncol Biol Phys. 1991 Feb;20(2):243-6. link to original article PubMed
1. Update: Bachaud JM, Cohen-Jonathan E, Alzieu C, David JM, Serrano E, Daly-Schveitzer N. Combined postoperative radiotherapy and weekly cisplatin infusion for locally advanced head and neck carcinoma: final report of a randomized trial. Int J Radiat Oncol Biol Phys. 1996 Dec 1;36(5):999-1004. link to original article contains verified protocol PubMed
Cooper JS, Pajak TF, Forastiere AA, Jacobs J, Campbell BH, Saxman SB, Kish JA, Kim HE, Cmelak AJ, Rotman M, Machtay M, Ensley JF, Chao KS, Schultz CJ, Lee N, Fu KK; Radiation Therapy Oncology Group 9501/Intergroup. Postoperative concurrent radiotherapy and chemotherapy for high-risk squamous-cell carcinoma of the head and neck. N Engl J Med. 2004 May 6;350(19):1937-44. link to original article contains verified protocol PubMed
1. Update: Cooper JS, Zhang Q, Pajak TF, Forastiere AA, Jacobs J, Saxman SB, Kish JA, Kim HE, Cmelak AJ, Rotman M, Lustig R, Ensley JF, Thorstad W, Schultz CJ, Yom SS, Ang KK. Long-term follow-up of the RTOG 9501/intergroup phase III trial: postoperative concurrent radiation therapy and chemotherapy in high-risk squamous cell carcinoma of the head and neck. Int J Radiat Oncol Biol Phys. 2012 Dec 1;84(5):1198-205. Epub 2012 Jun 30. link to original article contains verified protocol PubMed
Bernier J, Domenge C, Ozsahin M, Matuszewska K, Lefèbvre JL, Greiner RH, Giralt J, Maingon P, Rolland F, Bolla M, Cognetti F, Bourhis J, Kirkpatrick A, van Glabbeke M; European Organization for Research and Treatment of Cancer Trial 22931. Postoperative irradiation with or without concomitant chemotherapy for locally advanced head and neck cancer. N Engl J Med. 2004 May 6;350(19):1945-52. link to original article contains verified protocol PubMed
Posthoc analysis: Bernier J, Cooper JS, Pajak TF, van Glabbeke M, Bourhis J, Forastiere A, Ozsahin EM, Jacobs JR, Jassem J, Ang KK, Lefèbvre JL. Defining risk levels in locally advanced head and neck cancers: a comparative analysis of concurrent postoperative radiation plus chemotherapy trials of the EORTC (#22931) and RTOG (# 9501). Head Neck. 2005 Oct;27(10):843-50. link to original article PubMed

Radiation therapy

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Regimen

Study	Evidence	Comparator	Efficacy
Bachaud et al. 1991	Phase III	Cisplatin & RT	Inferior OS
Cooper et al. 2004 (RTOG 9501, ECOG R9501, SWOG 9515)	Phase III	Cisplatin & RT	Seems to have inferior DFS
Bernier et al. 2004 (EORTC 22931)	Phase III	Cisplatin & RT	Seems to have inferior OS

Used as a comparator arm; included for reference purposes only.

References

Bachaud JM, David JM, Boussin G, Daly N. Combined postoperative radiotherapy and weekly cisplatin infusion for locally advanced squamous cell carcinoma of the head and neck: preliminary report of a randomized trial. Int J Radiat Oncol Biol Phys. 1991 Feb;20(2):243-6. link to original article PubMed
1. Update: Bachaud JM, Cohen-Jonathan E, Alzieu C, David JM, Serrano E, Daly-Schveitzer N. Combined postoperative radiotherapy and weekly cisplatin infusion for locally advanced head and neck carcinoma: final report of a randomized trial. Int J Radiat Oncol Biol Phys. 1996 Dec 1;36(5):999-1004. link to original article contains verified protocol PubMed
Cooper JS, Pajak TF, Forastiere AA, Jacobs J, Campbell BH, Saxman SB, Kish JA, Kim HE, Cmelak AJ, Rotman M, Machtay M, Ensley JF, Chao KS, Schultz CJ, Lee N, Fu KK; Radiation Therapy Oncology Group 9501/Intergroup. Postoperative concurrent radiotherapy and chemotherapy for high-risk squamous-cell carcinoma of the head and neck. N Engl J Med. 2004 May 6;350(19):1937-44. link to original article contains verified protocol PubMed
1. Update: Cooper JS, Zhang Q, Pajak TF, Forastiere AA, Jacobs J, Saxman SB, Kish JA, Kim HE, Cmelak AJ, Rotman M, Lustig R, Ensley JF, Thorstad W, Schultz CJ, Yom SS, Ang KK. Long-term follow-up of the RTOG 9501/intergroup phase III trial: postoperative concurrent radiation therapy and chemotherapy in high-risk squamous cell carcinoma of the head and neck. Int J Radiat Oncol Biol Phys. 2012 Dec 1;84(5):1198-205. Epub 2012 Jun 30. link to original article contains verified protocol PubMed
Bernier J, Domenge C, Ozsahin M, Matuszewska K, Lefèbvre JL, Greiner RH, Giralt J, Maingon P, Rolland F, Bolla M, Cognetti F, Bourhis J, Kirkpatrick A, van Glabbeke M; European Organization for Research and Treatment of Cancer Trial 22931. Postoperative irradiation with or without concomitant chemotherapy for locally advanced head and neck cancer. N Engl J Med. 2004 May 6;350(19):1945-52. link to original article contains verified protocol PubMed
Posthoc analysis: Bernier J, Cooper JS, Pajak TF, van Glabbeke M, Bourhis J, Forastiere A, Ozsahin EM, Jacobs JR, Jassem J, Ang KK, Lefèbvre JL. Defining risk levels in locally advanced head and neck cancers: a comparative analysis of concurrent postoperative radiation plus chemotherapy trials of the EORTC (#22931) and RTOG (# 9501). Head Neck. 2005 Oct;27(10):843-50. link to original article PubMed

Locally advanced disease, chemotherapy & radiation therapy

Carboplatin & RT -> Carboplatin & Fluorouracil

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RT: Radiation Therapy

Regimen

Study	Evidence	Comparator	Efficacy
Chitapanarux et al. 2007	Phase III	Cisplatin & RT -> CF	Seems not superior

This study only involved patients with locally advanced nasopharyngeal cancer.

Chemoradiotherapy

Carboplatin (Paraplatin) 100 mg/m² IV over 1 hour once per day on days 1, 8, 15, 22, 29, 36
Concurrent radiation therapy to the primary tumor, 2 Gy fractions x 35 fractions (total dose: 70 Gy), given 5 times per week over 7 weeks

7-week course, followed by chemotherapy as described below

Chemotherapy

Chemotherapy starts 4 weeks after the end of radiation therapy.

Carboplatin (Paraplatin) AUC 5 IV once on day 1
Fluorouracil (5-FU) 1000 mg/m²/day IV continuous infusion over 96 hours on days 1 to 4 (total dose per cycle: 4000 mg/m²)

28-day cycle for 3 cycles

References

Chitapanarux I, Lorvidhaya V, Kamnerdsupaphon P, Sumitsawan Y, Tharavichitkul E, Sukthomya V, Ford J. Chemoradiotherapy comparing cisplatin versus carboplatin in locally advanced nasopharyngeal cancer: randomised, non-inferiority, open trial. Eur J Cancer. 2007 Jun;43(9):1399-406. Epub 2007 Apr 27. link to original article contains verified protocol PubMed

Carboplatin, Fluorouracil, RT

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RT: Radiation Therapy

Regimen

Study	Evidence	Comparator	Efficacy
Denis et al. 2004 (GORTEC 94-01)	Phase III	Radiation therapy	Seems to have superior OS
Bourhis et al. 2012 (GORTEC 99-02)	Phase III	Carboplatin, Fluorouracil, accelerated concurrent RT	Seems not superior
Bourhis et al. 2012 (GORTEC 99-02)	Phase III	Very accelerated radiation therapy	Seems to have superior PFS

Chemoradiotherapy

Carboplatin (Paraplatin) 70 mg/m² IV once per day on days 1 to 4, 22 to 25, 43 to 46
Fluorouracil (5-FU) 600 mg/m²/day IV continuous infusion on days 1 to 4, 22 to 25, 43 to 46 (total dose for each 4-day continuous infusion: 2400 mg/m²)
Concurrent radiation therapy, 2 Gy fractions x 35 fractions (total dose: 70 Gy), given 5 times per week over 7 weeks

7-week course of therapy

References

Denis F, Garaud P, Bardet E, Alfonsi M, Sire C, Germain T, Bergerot P, Rhein B, Tortochaux J, Calais G. Final results of the 94-01 French Head and Neck Oncology and Radiotherapy Group randomized trial comparing radiotherapy alone with concomitant radiochemotherapy in advanced-stage oropharynx carcinoma. J Clin Oncol. 2004 Jan 1;22(1):69-76. Epub 2003 Dec 2. link to original article contains verified protocol PubMed
Bourhis J, Sire C, Graff P, Grégoire V, Maingon P, Calais G, Gery B, Martin L, Alfonsi M, Desprez P, Pignon T, Bardet E, Rives M, Geoffrois L, Daly-Schveitzer N, Sen S, Tuchais C, Dupuis O, Guerif S, Lapeyre M, Favrel V, Hamoir M, Lusinchi A, Temam S, Pinna A, Tao YG, Blanchard P, Aupérin A. Concomitant chemoradiotherapy versus acceleration of radiotherapy with or without concomitant chemotherapy in locally advanced head and neck carcinoma (GORTEC 99-02): an open-label phase 3 randomised trial. Lancet Oncol. 2012 Feb;13(2):145-53. Epub 2012 Jan 18. link to original article contains verified protocol PubMed

Carboplatin, Paclitaxel, RT

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RT: Radiation Therapy

Regimen #1, accelerated hyperfractionated RT

Study	Evidence
Carter et al. 2008	Phase II

Chemoradiotherapy

Carboplatin (Paraplatin) AUC 1 IV once per week
Paclitaxel (Taxol) 40 mg/m² IV once per week
Concurrent radiation therapy, 1.2 Gy BID fractions (total dose: 69.6 Gy)

6-week course of therapy

Regimen #2, standard RT

Study	Evidence
Conley et al. 1997	Pilot, <20 patients
Suntharalingam et al. 2000	Phase II

Chemoradiotherapy

Carboplatin (Paraplatin) 100 mg/m² IV once per week, given prior to radiation therapy
Paclitaxel (Taxol) 40 mg/m² IV once per week, given prior to radiation therapy
- According to Conley et al. 1997, the initial dose of paclitaxel was 45 mg/m², but 40 mg/m² was subsequently used
Concurrent radiation therapy, 1.8 Gy fractions x 39 fractions (total dose: 70.2 Gy), given 5 times per week

Supportive medications

Dexamethasone (Decadron) 20 mg (route not specified) given twice, 12 and 6 hours prior to chemotherapy
Diphenhydramine (Benadryl) 50 mg IV once prior to chemotherapy
Ranitidine (Zantac) 50 mg IV once prior to chemotherapy
Granisetron (Kytril) 1 mg IV once prior to chemotherapy

7.5-week course of therapy

References

Conley B, Jacobs M, Suntharalingam M, Zacharski D, Ord RA, Gray W, Aisner J. A pilot trial of paclitaxel, carboplatin, and concurrent radiotherapy for unresectable squamous cell carcinoma of the head and neck. Semin Oncol. 1997 Feb;24(1 Suppl 2):S2-78-S2-80. contains protocol PubMed
Suntharalingam M, Haas ML, Conley BA, Egorin MJ, Levy S, Sivasailam S, Herman JM, Jacobs MC, Gray WC, Ord RA, Aisner JA, Van Echo DA. The use of carboplatin and paclitaxel with daily radiotherapy in patients with locally advanced squamous cell carcinomas of the head and neck. Int J Radiat Oncol Biol Phys. 2000 Apr 1;47(1):49-56. link to original article contains verified protocol PubMed
Carter DL, Asmar L, Barrera D, Caracandas J, Dakhil JS, McCracken D, O'Rourke MA, Rosenberg RK, Boehm KA, Ilegbodu D, Reid RL. Favorable survival observed after carboplatin, paclitaxel, and concurrent accelerated hyperfractionated radiotherapy for treatment of locally advanced head and neck carcinoma. Invest New Drugs. 2008 Oct;26(5):473-81. Epub 2008 May 13. link to original article contains protocol PubMed

Cetuximab & RT

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RT: Radiation Therapy

Regimen

Study	Evidence	Comparator	Efficacy
Bonner et al. 2006 (IMCL-9815)	Phase III	Radiation therapy	Seems to have superior OS

Chemoradiotherapy

Cetuximab (Erbitux) 400 mg/m² IV over 2 hours once 1 week before radiation therapy begins; then 250 mg/m² IV over 1 hour once per week during course of radiation therapy
- A test dose of 20 mg IV over 10 minutes, followed by 30 minutes of observation, was given prior to the first full dose of cetuximab
Concurrent radiation therapy with one of the following regimens:
- "Once per day" regimen: Concurrent radiation therapy, 2 Gy fractions x 35 fractions (total dose: 70 Gy), given once per day 5 times per week over 7 weeks
- "Twice per day" regimen: Concurrent radiation therapy, 1.2 Gy fractions x 60 to 64 fractions (total dose: 72 to 76.8 Gy), given twice per day for a total of 10 times per week over 6 to 6.5 weeks
- "Concomitant boost" regimen: Concurrent radiation therapy, 1.8 Gy fractions x 18 fractions (total dose: 32.4 Gy), given once per day 5 times per week for 3.6 weeks; and twice per day fractions:
  - Morning dose: 1.8 Gy fractions x 12 fractions (total dose: 21.6 Gy), given 5 days per week over 2.4 weeks
  - Afternoon dose: 1.5 Gy fractions x 12 fractions (total dose: 18 Gy), given 5 days per week over 2.4 weeks
  - Total dose for concomitant boost regimen: 72 Gy

Supportive medications

Diphenhydramine (Benadryl) 50 mg (route not specified) "or an equivalent histamine H1–receptor antagonist" prior to Cetuximab (Erbitux)

References

Bonner JA, Harari PM, Giralt J, Azarnia N, Shin DM, Cohen RB, Jones CU, Sur R, Raben D, Jassem J, Ove R, Kies MS, Baselga J, Youssoufian H, Amellal N, Rowinsky EK, Ang KK. Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med. 2006 Feb 9;354(6):567-78. link to original article contains verified protocol PubMed
1. QoL Analysis: Curran D, Giralt J, Harari PM, Ang KK, Cohen RB, Kies MS, Jassem J, Baselga J, Rowinsky EK, Amellal N, Comte S, Bonner JA. Quality of life in head and neck cancer patients after treatment with high-dose radiotherapy alone or in combination with cetuximab. J Clin Oncol. 2007 Jun 1;25(16):2191-7. link to original article contains partial protocol PubMed
2. Update: Bonner JA, Harari PM, Giralt J, Cohen RB, Jones CU, Sur RK, Raben D, Baselga J, Spencer SA, Zhu J, Youssoufian H, Rowinsky EK, Ang KK. Radiotherapy plus cetuximab for locoregionally advanced head and neck cancer: 5-year survival data from a phase 3 randomised trial, and relation between cetuximab-induced rash and survival. Lancet Oncol. 2010 Jan;11(1):21-8. Epub 2009 Nov 10. link to original article contains partial protocol PubMed
3. Retrospective subgroup analysis: Rosenthal DI, Harari PM, Giralt J, Bell D, Raben D, Liu J, Schulten J, Ang KK, Bonner JA. Association of Human Papillomavirus and p16 Status With Outcomes in the IMCL-9815 Phase III Registration Trial for Patients With Locoregionally Advanced Oropharyngeal Squamous Cell Carcinoma of the Head and Neck Treated With Radiotherapy With or Without Cetuximab. J Clin Oncol. 2016 Apr 20;34(12):1300-8. Epub 2015 Dec 28. link to original article PubMed

CF -> Carboplatin & RT

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CF -> Carboplatin & RT: Cisplatin and Fluorouracil followed by Carboplatin and Radiation Therapy

Regimen

Study	Evidence	Comparator	Efficacy
Posner et al. 2007 (TAX 324)	Phase III	TPF -> Carboplatin & RT	Inferior OS

Chemotherapy

Cisplatin (Platinol) 100 mg/m² IV over 30 to 180 minutes once on day 1, given first
Fluorouracil (5-FU) 1000 mg/m²/day IV continuous infusion over 96 hours on days 1 to 4 (total dose per cycle: 4000 mg/m²)

21-day cycle for 3 cycles; then start chemoradiotherapy 3 to 8 weeks after the start of cycle 3:

Chemoradiotherapy

Carboplatin (Paraplatin) AUC 1.5 IV over 1 hour once per day on days 1, 8, 15, 22, 29, 36, 43
Concurrent radiation therapy, 2 Gy fractions x 35 to 37 fractions (total dose: 70 to 74 Gy), given 5 times per week over 7 to 7.5 weeks

7 to 7.5-week course; surgery "performed 6 to 12 weeks after completion of chemoradiotherapy for patients who had an initial nodal stage of N2 and a partial response to induction chemotherapy, N3 disease, or residual disease after chemoradiotherapy."

References

Posner MR, Hershock DM, Blajman CR, Mickiewicz E, Winquist E, Gorbounova V, Tjulandin S, Shin DM, Cullen K, Ervin TJ, Murphy BA, Raez LE, Cohen RB, Spaulding M, Tishler RB, Roth B, Viroglio Rdel C, Venkatesan V, Romanov I, Agarwala S, Harter KW, Dugan M, Cmelak A, Markoe AM, Read PW, Steinbrenner L, Colevas AD, Norris CM Jr, Haddad RI; TAX 324 Study Group. Cisplatin and fluorouracil alone or with docetaxel in head and neck cancer. N Engl J Med. 2007 Oct 25;357(17):1705-15. link to original article contains verified protocol PubMed

CF -> Cisplatin & RT

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CF -> Cisplatin & RT: Cisplatin and Fluorouracil followed by Cisplatin and Radiation Therapy

Regimen

Study	Evidence	Comparator	Efficacy
Hitt et al. 2005	Phase III	PCF -> Cisplatin & RT	Inferior CR rate

Chemotherapy

Cisplatin (Platinol) 100 mg/m² IV once on day 1
Fluorouracil (5-FU) 1000 mg/m²/day IV continuous infusion over 5 days on days 1 to 5 (total dose per cycle: 5000 mg/m²)

3-week cycle for 3 cycles

Patients then undergo ENT evaluation and CT imaging of the primary tumor and neck. Patients with complete response (CR) or partial response of >80% in the primary tumor and no evidence of progression in neck lymph nodes proceeded to chemoradiotherapy. "Patients with a PR of less than 80% or stable disease in the neck lymph nodes (especially if N2 or N3 disease) after induction CT were referred to surgery for neck dissection, if the surgeons were in agreement, before the administration of CRT." Patients with no response or progression of disease were taken off study.

Chemoradiotherapy

Cisplatin (Platinol) 100 mg/m² IV once per day on days 1, 22, 43
Concurrent radiation therapy to primary tumor, 2 Gy fractions x 35 fractions (total dose: 70 Gy), given 5 times per week over 7 weeks. Nodal areas not involved by tumor received 50 Gy.

References

Hitt R, López-Pousa A, Martínez-Trufero J, Escrig V, Carles J, Rizo A, Isla D, Vega ME, Martí JL, Lobo F, Pastor P, Valentí V, Belón J, Sánchez MA, Chaib C, Pallarés C, Antón A, Cervantes A, Paz-Ares L, Cortés-Funes H. 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 Dec 1;23(34):8636-45. Epub 2005 Nov 7. link to original article contains verified protocol PubMed

CF & RT

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CF & RT: Cisplatin and Fluorouracil with concurrent Radiation Therapy

Regimen #1

Study	Evidence	Comparator	Efficacy
Taylor et al. 1994	Phase III	CF -> RT	Superior ORR

Chemotherapy

Cisplatin (Platinol) 60 mg/m² IV over 15 minutes once on day 1
Fluorouracil (5-FU) 800 mg/m²/day IV continuous infusion over 120 hours on days 1 to 5 (total dose per cycle: 4000 mg/m²)

2-week cycle for 7 cycles given together with the following concurrent radiation therapy:

Radiotherapy

Concurrent radiation therapy, 2 Gy fractions x 35 fractions (total dose: 70 Gy), given 5 times per week on weeks 1, 3, 5, 7, 9, 11, 13

Regimen #2

Study	Evidence	Comparator	Efficacy
Garden et al. 2004 (RTOG 97-03)	Randomized Phase II	Cisplatin, Paclitaxel, RT	Seems not superior
Garden et al. 2004 (RTOG 97-03)	Randomized Phase II	5-FU, Hydroxyurea, RT	Seems not superior

Note: Garden et al. 2004 described this regimen in an unclear way, and it is not clear exactly how many doses or when each chemotherapy is given. Specifically, it's confusing how people would "receive their treatments every week for 7 consecutive weeks," yet fluorouracil (and maybe also cisplatin) would be given "daily for the final 10 days of radiation treatment."

Chemoradiotherapy

Cisplatin (Platinol) 10 mg/m² IV once per day (unable to discern what days this is given on based on the paper)
Fluorouracil (5-FU) 400 mg/m²/day IV continuous infusion over 10 days on the last 10 days of radiation treatments
Concurrent radiation therapy, 2 Gy fractions x 35 fractions (total dose: 70 Gy), given 5 times per week over 7 weeks

7-week course of therapy

References

Taylor SG 4th, Murthy AK, Vannetzel JM, Colin P, Dray M, Caldarelli DD, Shott S, Vokes E, Showel JL, Hutchinson JC et al. Randomized comparison of neoadjuvant cisplatin and fluorouracil infusion followed by radiation versus concomitant treatment in advanced head and neck cancer. J Clin Oncol. 1994 Feb;12(2):385-95. link to original article contains verified protocol PubMed
Adelstein DJ, Li Y, Adams GL, Wagner H Jr, Kish JA, Ensley JF, Schuller DE, Forastiere AA. 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 Jan 1;21(1):92-8. link to original article PubMed
Garden AS, Harris J, Vokes EE, Forastiere AA, Ridge JA, Jones C, Horwitz EM, Glisson BS, Nabell L, Cooper JS, Demas W, Gore E. Preliminary results of Radiation Therapy Oncology Group 97-03: a randomized phase ii trial of concurrent radiation and chemotherapy for advanced squamous cell carcinomas of the head and neck. J Clin Oncol. 2004 Jul 15;22(14):2856-64. link to original article contains verified protocol--see comment above PubMed

CF -> RT

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CF -> RT: Cisplatin and Fluorouracil followed by Radiation Therapy

Regimen #1

Study	Evidence	Comparator	Efficacy
Forastiere et al. 2003 (RTOG 91-11)	Phase III	Cisplatin & RT	Not reported
Forastiere et al. 2003 (RTOG 91-11)	Phase III	Radiation therapy	Seems to have superior DFS

Chemotherapy

Cisplatin (Platinol) 100 mg/m² IV once on day 1
Fluorouracil (5-FU) 1000 mg/m²/day IV continuous infusion over 120 hours on days 1 to 5 (total dose per cycle: 5000 mg/m²)

21-day cycle for 2 cycles

After cycle 2, patients are evaluated by indirect laryngoscopy and CT neck. Patients with complete or partial response receive a third cycle of induction chemotherapy as described above, followed by radiation therapy. Patients with worse than a partial response underwent laryngectomy and adjuvant radiation therapy.

Radiotherapy

Radiation therapy, 2 Gy fractions x 35 fractions (total dose: 70 Gy), given 5 times per week over 7 weeks

Regimen #2

Study	Evidence	Comparator	Efficacy
Taylor et al. 1994	Phase III	CF & RT	Inferior ORR

Chemotherapy

Cisplatin (Platinol) 100 mg/m² IV over 15 minutes once on day 1
Fluorouracil (5-FU) 1000 mg/m²/day IV continuous infusion over 120 hours on days 1 to 5 (total dose per cycle: 5000 mg/m²)

21-day cycle for 3 cycles, followed by:

Radiotherapy

Radiation therapy, 1.8 to 2 Gy fractions to a total dose of 70 Gy, given 5 times per week over 7 to 8 weeks

Regimen #3

Study	Evidence	Comparator	Efficacy
Pointreau et al. 2009 (GORTEC)	Phase III	TPF -> RT	Inferior ORR

Chemotherapy

Cisplatin (Platinol) 100 mg/m² IV over 1 hour once on day 1
Fluorouracil (5-FU) 1000 mg/m²/day IV continuous infusion over 5 days on days 1 to 5 (total dose per cycle: 5000 mg/m²)

Supportive medications

Normal saline (use of mannitol, KCl, and magnesium sulfate per institutional protocol) 1000 mL IV given twice, before and after Cisplatin (Platinol)

21-day cycle for 3 cycles

Patients who responded to induction chemotherapy proceeded to radiation therapy within 3 to 7 weeks of finishing chemotherapy. Patients who did not respond to induction chemotherapy proceeded to surgery and postoperative radiotherapy (see Pointreau et al. 2009 for details).

Radiotherapy

Radiation therapy to the primary tumor and involved lymph nodes, 2 Gy fractions x 35 fractions (total dose: 70 Gy), given 5 times per week over 7 weeks. Prophylactic radiation to the volume at risk for microscopic disease, 2 Gy fractions x 25 to 27 fractions (total dose: 50 to 54 Gy), given 5 times per week.
"Chemotherapy (cisplatin, carboplatin, and 5-fluorouracil or a combination of two drugs) during radiotherapy was allowed for all patients who were treated at the same institute, according to its practice." No further details available.

Regimen #4

Study	Evidence	Comparator	Efficacy
Vermorken et al. 2007 (EORTC 24971/TAX 323)	Phase III	TPF -> RT	Seems to have inferior OS

Chemotherapy

Cisplatin (Platinol) 100 mg/m² IV over 1 hour once on day 1, given first before fluorouracil
Fluorouracil (5-FU) 1000 mg/m²/day IV continuous infusion over 5 days on days 1 to 5 (total dose per cycle: 5000 mg/m²)

Supportive medications

"Adequate antiemetic medications during chemotherapy"
Prophylactic granulocyte colony-stimulating factor only allowed for patients who had "febrile neutropenia or infection, a delay in recovery of the absolute neutrophil count at day 28, or grade 4 neutropenia persisting for 7 days or more."

21-day cycle for 4 cycles

Patients without progressive disease and who had recovery of marrow function, resolution of mucositis, and healed from any dental procedures started radiation therapy within 4 to 7 weeks of finishing chemotherapy:

Radiotherapy

Radiation therapy over 7 weeks with one of the following (further details not provided):
- Conventional fractionation, total dose 66 to 70 Gy
- Accelerated fractionation, total dose 70 Gy
- Hyperfractionated, total dose 74 Gy

References

Taylor SG 4th, Murthy AK, Vannetzel JM, Colin P, Dray M, Caldarelli DD, Shott S, Vokes E, Showel JL, Hutchinson JC et al. Randomized comparison of neoadjuvant cisplatin and fluorouracil infusion followed by radiation versus concomitant treatment in advanced head and neck cancer. J Clin Oncol. 1994 Feb;12(2):385-95. link to original article contains verified protocol PubMed
Forastiere AA, Goepfert H, Maor M, Pajak TF, Weber R, Morrison W, Glisson B, Trotti A, Ridge JA, Chao C, Peters G, Lee DJ, Leaf A, Ensley J, Cooper J. Concurrent chemotherapy and radiotherapy for organ preservation in advanced laryngeal cancer. N Engl J Med. 2003 Nov 27;349(22):2091-8. link to original article contains verified protocol PubMed
1. Update: Forastiere AA, Zhang Q, Weber RS, Maor MH, Goepfert H, Pajak TF, Morrison W, Glisson B, Trotti A, Ridge JA, Thorstad W, Wagner H, Ensley JF, Cooper JS. Long-term results of RTOG 91-11: a comparison of three nonsurgical treatment strategies to preserve the larynx in patients with locally advanced larynx cancer. J Clin Oncol. 2013 Mar 1;31(7):845-52. Epub 2012 Nov 26. link to original article contains partial protocol PubMed
Vermorken JB, Remenar E, van Herpen C, Gorlia T, Mesia R, Degardin M, Stewart JS, Jelic S, Betka J, Preiss JH, van den Weyngaert D, Awada A, Cupissol D, Kienzer HR, Rey A, Desaunois I, Bernier J, Lefebvre JL; EORTC 24971/TAX 323 Study Group. Cisplatin, fluorouracil, and docetaxel in unresectable head and neck cancer. N Engl J Med. 2007 Oct 25;357(17):1695-704. link to original article contains verified protocol PubMed
1. QoL Analysis: van Herpen CM, Mauer ME, Mesia R, Degardin M, Jelic S, Coens C, Betka J, Bernier J, Remenar E, Stewart JS, Preiss JH, van den Weyngaert D, Bottomley A, Vermorken JB; EORTC Head and Neck Group. Short-term health-related quality of life and symptom control with docetaxel, cisplatin, 5-fluorouracil and cisplatin (TPF), 5-fluorouracil (PF) for induction in unresectable locoregionally advanced head and neck cancer patients (EORTC 24971/TAX 323). Br J Cancer. 2010 Oct 12;103(8):1173-81. Epub 2010 Sep 14. link to original article contains verified protocol PubMed
Pointreau Y, Garaud P, Chapet S, Sire C, Tuchais C, Tortochaux J, Faivre S, Guerrif S, Alfonsi M, Calais G. Randomized trial of induction chemotherapy with cisplatin and 5-fluorouracil with or without docetaxel for larynx preservation. J Natl Cancer Inst. 2009 Apr 1;101(7):498-506. Epub 2009 Mar 24. link to original article contains verified protocol PubMed

Cisplatin & RT

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RT: Radiation Therapy

Regimen #1

Study	Evidence	Comparator	Efficacy
Adelstein et al. 2003	Phase III	CF & RT	Seems not superior
Adelstein et al. 2003	Phase III	Radiation therapy	Seems to have superior OS
Forastiere et al. 2003 (RTOG 91-11)	Phase III	CF -> RT	Not reported
Forastiere et al. 2003 (RTOG 91-11)	Phase III	Radiation therapy	Superior DFS
Sun et al. 2016	Phase III	TPF -> Cisplatin & RT	Seems to have inferior FFS

Chemoradiotherapy

Cisplatin (Platinol) 100 mg/m² IV once per day on days 1, 22, 43
Concurrent radiation therapy as follows:
- Adelstein et al. 2003 and RTOG 91-11: 2 Gy fractions x 35 fractions (total dose: 70 Gy), given 5 times per week over 7 weeks
- Sun et al. 2016: see paper for details

One course

Regimen #2

Study	Evidence	Comparator	Efficacy
Ang et al. 2014 (RTOG 0522)	Phase III	Cetuximab, Cisplatin, RT	Seems not superior

Chemoradiotherapy

Cisplatin (Platinol) 100 mg/m² IV once per day on days 1 & 22
Concurrent radiation therapy by one of the following:
- IMRT: 2 Gy fractions x 35 fractions (total dose: 70 Gy), given 6 times per week over 6 weeks
- Accelerated radiotherapy: 42 fractions (total dose: 72 Gy), given twice per day for 12 days then once per day over 6 weeks

One course

Regimen #3

Study	Evidence	Comparator	Efficacy
Chan et al. 2005	Phase III	Radiation therapy	Might have superior OS

This study only involved patients with locoregionally advanced nasopharyngeal carcinoma.

Chemoradiotherapy

Cisplatin (Platinol) 40 mg/m² in 1 liter normal saline IV over 2 hours once per day on days 1, 8, 15, 22, 29, 36, 43
Concurrent radiation therapy, 2 Gy fractions x 33 fractions (total dose: 66 Gy), given 5 times per week over 6.5 weeks. See Chan et al. 2005 for additional information about boost doses.

One course

References

Adelstein DJ, Li Y, Adams GL, Wagner H Jr, Kish JA, Ensley JF, Schuller DE, Forastiere AA. 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 Jan 1;21(1):92-8. link to original article contains verified protocol PubMed
Forastiere AA, Goepfert H, Maor M, Pajak TF, Weber R, Morrison W, Glisson B, Trotti A, Ridge JA, Chao C, Peters G, Lee DJ, Leaf A, Ensley J, Cooper J. Concurrent chemotherapy and radiotherapy for organ preservation in advanced laryngeal cancer. N Engl J Med. 2003 Nov 27;349(22):2091-8. link to original article contains verified protocol PubMed
1. Update: Forastiere AA, Zhang Q, Weber RS, Maor MH, Goepfert H, Pajak TF, Morrison W, Glisson B, Trotti A, Ridge JA, Thorstad W, Wagner H, Ensley JF, Cooper JS. Long-term results of RTOG 91-11: a comparison of three nonsurgical treatment strategies to preserve the larynx in patients with locally advanced larynx cancer. J Clin Oncol. 2013 Mar 1;31(7):845-52. Epub 2012 Nov 26. link to original article contains partial protocol PubMed
Chan AT, Leung SF, Ngan RK, Teo PM, Lau WH, Kwan WH, Hui EP, Yiu HY, Yeo W, Cheung FY, Yu KH, Chiu KW, Chan DT, Mok TS, Yau S, Yuen KT, Mo FK, Lai MM, Ma BB, Kam MK, Leung TW, Johnson PJ, Choi PH, Zee BC. Overall survival after concurrent cisplatin-radiotherapy compared with radiotherapy alone in locoregionally advanced nasopharyngeal carcinoma. J Natl Cancer Inst. 2005 Apr 6;97(7):536-9. link to original article contains verified protocol PubMed
Ang KK, Zhang Q, Rosenthal DI, Nguyen-Tan PF, Sherman EJ, Weber RS, Galvin JM, Bonner JA, Harris J, El-Naggar AK, Gillison ML, Jordan RC, Konski AA, Thorstad WL, Trotti A, Beitler JJ, Garden AS, Spanos WJ, Yom SS, Axelrod RS. Randomized phase III trial of concurrent accelerated radiation plus cisplatin with or without cetuximab for stage III to IV head and neck carcinoma: RTOG 0522. J Clin Oncol. 2014 Sep 20;32(27):2940-50. link to original article contains verified protocol PubMed
Sun Y, Li WF, Chen NY, Zhang N, Hu GQ, Xie FY, Sun Y, Chen XZ, Li JG, Zhu XD, Hu CS, Xu XY, Chen YY, Hu WH, Guo L, Mo HY, Chen L, Mao YP, Sun R, Ai P, Liang SB, Long GX, Zheng BM, Feng XL, Gong XC, Li L, Shen CY, Xu JY, Guo Y, Chen YM, Zhang F, Lin L, Tang LL, Liu MZ, Ma J. Induction chemotherapy plus concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: a phase 3, multicentre, randomised controlled trial. Lancet Oncol. 2016 Sep 26. [Epub ahead of print] link to original article contains verified protocol PubMed

Cisplatin & RT -> CF

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Cisplatin & RT -> CF: Cisplatin and Radiation Therapy followed by Cisplatin and Fluorouracil

Regimen #1

Study	Evidence	Comparator	Efficacy
Al-Sarraf et al. 1998 (Intergroup 0099)	Phase III	Radiation therapy	Superior OS

This study only involved patients with stage III and IV nasopharynx cancers without evidence of metastases.

Chemoradiotherapy

Cisplatin (Platinol) 100 mg/m² IV over 15 to 20 minutes once per day on days 1, 22, 43
Concurrent radiation therapy to the primary tumor, 1.8 to 2 Gy fractions x 35 to 39 fractions (total dose: 70 Gy), given 5 times per week. Minimum total dose to neck nodes is 50 Gy for N0 disease; 66 Gy for nodes =2 cm in size; 70 Gy for nodes >2 cm.

Supportive medications

Forced hydration: 5% dextrose in 1/2 normal saline with 40 mEq KCl, 2000 mL IV continuous infusion over 24 hours given twice, before each dose of Cisplatin (Platinol) and after the second mannitol infusion
Mannitol 12.5 g IV bolus prior to Cisplatin (Platinol)
5% dextrose in 1/2 normal saline with 30 mEq KCl and mannitol 25 g, 1000 mL IV over 4 hours immediately after Cisplatin (Platinol)
Antiemetic such as Prochlorperazine (Compazine) 25 mg rectal suppository given 30 minutes prior to Cisplatin (Platinol); Prochlorperazine (Compazine) 10 mg IM every 4 hours as needed for nausea after Cisplatin (Platinol)

7 to 8-week course, followed 4 weeks after the last dose of cisplatin used in Chemoradiotherapy by:

Chemotherapy

Cisplatin (Platinol) 80 mg/m² IV over 15 to 20 minutes once on day 1
Fluorouracil (5-FU) 1000 mg/m²/day IV continuous infusion over 96 hours on days 1 to 4 (total dose per cycle: 4000 mg/m²)

Supportive medications

Al-Sarraf et al. 1998 did not specifically say whether the same hydration and antiemetics were used for this chemotherapy as in Chemoradiotherapy.

28-day cycle for 3 cycles

Regimen #2

Study	Evidence	Comparator	Efficacy
Chitapanarux et al. 2007	Phase III	Carboplatin & RT -> Carboplatin & 5-FU	Seems not superior

This study only involved patients with locoregionally advanced nasopharyngeal carcinoma.

Chemoradiotherapy

Cisplatin (Platinol) 100 mg/m² IV over 3 hours once per day on days 1, 22, 43
Concurrent radiation therapy to the primary tumor, 2 Gy fractions x 35 fractions (total dose: 70 Gy), given 5 times per week over 7 weeks

7-week course, followed 4 weeks after the end of radiation therapy by:

Chemotherapy

Cisplatin (Platinol) 80 mg/m² IV once on day 1
Fluorouracil (5-FU) 1000 mg/m²/day IV continuous infusion over 96 hours on days 1 to 4 (total dose per cycle: 4000 mg/m²)

28-day cycle for 3 cycles

References

Al-Sarraf M, LeBlanc M, Giri PG, Fu KK, Cooper J, Vuong T, Forastiere AA, Adams G, Sakr WA, Schuller DE, Ensley JF. Chemoradiotherapy versus radiotherapy in patients with advanced nasopharyngeal cancer: phase III randomized Intergroup study 0099. J Clin Oncol. 1998 Apr;16(4):1310-7. link to original article contains verified protocol PubMed
Chitapanarux I, Lorvidhaya V, Kamnerdsupaphon P, Sumitsawan Y, Tharavichitkul E, Sukthomya V, Ford J. Chemoradiotherapy comparing cisplatin versus carboplatin in locally advanced nasopharyngeal cancer: randomised, non-inferiority, open trial. Eur J Cancer. 2007 Jun;43(9):1399-406. Epub 2007 Apr 27. link to original article contains verified protocol PubMed

Cisplatin, Paclitaxel, RT

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RT: Radiation Therapy

Regimen

Study	Evidence	Comparator	Efficacy
Garden et al. 2004 (RTOG 97-03)	Randomized Phase II	CF & RT	Seems not superior
Garden et al. 2004 (RTOG 97-03)	Randomized Phase II	5-FU, Hydroxyurea, RT	Seems not superior

Chemoradiotherapy

Cisplatin (Platinol) 20 mg/m² IV once each Tuesday on weeks 1 to 7, given prior to radiation
Paclitaxel (Taxol) 30 mg/m² IV once each Monday on weeks 1 to 7, given prior to radiation
Concurrent radiation therapy, 2 Gy fractions x 35 fractions (total dose: 70 Gy), given 5 times per week over 7 weeks

7-week course of therapy

References

Garden AS, Harris J, Vokes EE, Forastiere AA, Ridge JA, Jones C, Horwitz EM, Glisson BS, Nabell L, Cooper JS, Demas W, Gore E. Preliminary results of Radiation Therapy Oncology Group 97-03: a randomized phase ii trial of concurrent radiation and chemotherapy for advanced squamous cell carcinomas of the head and neck. J Clin Oncol. 2004 Jul 15;22(14):2856-64. link to original article contains verified protocol PubMed

Fluorouracil, Hydroxyurea, RT

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RT: Radiation Therapy

Regimen

Study	Evidence	Comparator	Efficacy
Garden et al. 2004 (RTOG 97-03)	Randomized Phase II	CF & RT	Seems not superior
Garden et al. 2004 (RTOG 97-03)	Randomized Phase II	Cisplatin, Paclitaxel, RT	Seems not superior

Chemoradiotherapy

Fluorouracil (5-FU) 800 mg/m²/day IV continuous infusion given 5 days per week on weeks 1, 3, 5, 7, 9, 11, 13 (total dose per week: 4000 mg/m²)
- Note: Garden et al. 2004 was not clear about the exact schedule nor duration of the continuous infusion, such as whether each continuous infusion was over 24 hours or not
Hydroxyurea (Hydrea) 1000 mg PO every 12 hours x 11 doses per week on weeks 1, 3, 5, 7, 9, 11, 13 (total dose per week: 11,000 mg)
- Note: Garden et al. 2004 did not clearly specify when the doses of hydroxyurea were to be taken in relation to radiation treatments
Concurrent radiation therapy, 2 Gy fractions x 35 fractions (total dose: 70 Gy), given 5 times per week on weeks 1, 3, 5, 7, 9, 11, 13

13-week course of therapy

References

Garden AS, Harris J, Vokes EE, Forastiere AA, Ridge JA, Jones C, Horwitz EM, Glisson BS, Nabell L, Cooper JS, Demas W, Gore E. Preliminary results of Radiation Therapy Oncology Group 97-03: a randomized phase ii trial of concurrent radiation and chemotherapy for advanced squamous cell carcinomas of the head and neck. J Clin Oncol. 2004 Jul 15;22(14):2856-64. link to original article contains verified protocol PubMed

PCF -> Cisplatin & RT

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PCF: Paclitaxel, Cisplatin, Fluorouracil
PPF: Paclitaxel, Platinol (Cisplatin), Fluorouracil
RT: Radiation Therapy

Regimen

Study	Evidence	Comparator	Efficacy
Hitt et al. 2005	Phase III	CF -> Cisplatin & RT	Superior CR rate

Chemotherapy

Paclitaxel (Taxol) 175 mg/m² IV over 3 hours once on day 1
Cisplatin (Platinol) 100 mg/m² IV once on day 2
Fluorouracil (5-FU) 500 mg/m²/day IV continuous infusion over 5 days on days 2 to 6 (total dose per cycle: 2500 mg/m²)

Supportive medications

"Standard intravenous premedications with Dexamethasone (Decadron), Diphenhydramine (Benadryl), and Cimetidine (Tagamet) or Ranitidine (Zantac) were administered 30 minutes before Paclitaxel (Taxol) infusion to prevent hypersensitivity reactions."

3-week cycle for 3 cycles

Patients then undergo ENT evaluation and CT imaging of the primary tumor and neck. Patients with complete response (CR) or partial response of >80% in the primary tumor and no evidence of progression in neck lymph nodes proceeded to chemoradiotherapy. "Patients with a PR of less than 80% or stable disease in the neck lymph nodes (especially if N2 or N3 disease) after induction CT were referred to surgery for neck dissection, if the surgeons were in agreement, before the administration of CRT." Patients with no response or progression of disease were taken off study.

Chemoradiotherapy

Cisplatin (Platinol) 100 mg/m² IV once per day on days 1, 22, 43
Concurrent radiation therapy to primary tumor, 2 Gy fractions x 35 fractions (total dose: 70 Gy), given 5 times per week over 7 weeks. Nodal areas not involved by tumor received 50 Gy.

References

Hitt R, López-Pousa A, Martínez-Trufero J, Escrig V, Carles J, Rizo A, Isla D, Vega ME, Martí JL, Lobo F, Pastor P, Valentí V, Belón J, Sánchez MA, Chaib C, Pallarés C, Antón A, Cervantes A, Paz-Ares L, Cortés-Funes H. 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 Dec 1;23(34):8636-45. Epub 2005 Nov 7. link to original article contains verified protocol PubMed

PCF -> Paclitaxel & RT

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PCF: Paclitaxel, Cisplatin, Fluorouracil
PPF: Paclitaxel, Platinol, Fluorouracil
RT: Radiation Therapy

Regimen

Study	Evidence
Hitt et al. 2002	Phase II

Chemotherapy

Paclitaxel (Taxol) 175 mg/m² IV over 3 hours once on day 1
Cisplatin (Platinol) 100 mg/m² IV over 1 hour once on day 2
Fluorouracil (5-FU) 500 mg/m²/day IV continuous infusion over 5 days on days 2 to 6 (total dose per cycle: 2500 mg/m²)

Supportive medications

Dexamethasone (Decadron) 20 mg IV once 30 minutes prior to Paclitaxel (Taxol)
Dexamethasone (Decadron) 8 mg PO BID on days 2 & 3
Ondansetron (Zofran) 8 mg IV/PO Q8H or Q12H on days 1 to 5
Diphenhydramine (Benadryl) 50 mg IV once 30 minutes prior to Paclitaxel (Taxol)
Cimetidine (Tagamet) 300 mg IV once 30 minutes prior to Paclitaxel (Taxol)
- Per Hitt et al. 2005, Ranitidine (Zantac) (dose not specified) could be used instead
Mannitol and IV hydration with Cisplatin (Platinol)

3-week cycle for 3 cycles

Patients undergo ENT evaluation and CT imaging of the primary tumor and neck during week 3 or 4 of cycle 3. Patients who did not have at least a partial response were recommended for surgery. Patients with bulky nodal disease prior to therapy "and/or suboptimal response to induction chemotherapy" were recommended for neck dissection before radiation therapy. Surgery was performed 4 weeks after cycle 3 day 1. Patients with complete response (CR) or partial response proceeded to chemoradiotherapy; radiation therapy alone was used "if concomitant treatment was not feasible."

Chemoradiotherapy

Chemoradiotherapy starts 4 to 6 weeks after cycle 3 day 1 or as soon as patients recover from surgery (if any).

Paclitaxel (Taxol) 25 mg/m² IV over 1 hour once per week during radiation therapy, starting on day 1
Concurrent radiation therapy to primary unresected tumors, 1.8 to 2 Gy fractions (total dose: 65 to 70 Gy). Post-operative areas received 60 Gy. Nodal areas not involved by tumor received at least 45 Gy.

Supportive medications

"Usual pre-medication was given before each paclitaxel infusion" (presumably the same ones used during induction chemotherapy).

References

Hitt R, Paz-Ares L, Brandáriz A, Castellano D, Peña C, Millán JM, Calvo F, Ortiz de Urbina D, López E, Alvarez-Vicent JJ, Cortés-Funes H. Induction chemotherapy with paclitaxel, cisplatin and 5-fluorouracil for squamous cell carcinoma of the head and neck: long-term results of a phase II trial. Ann Oncol. 2002 Oct;13(10):1665-73. link to original article contains verified protocol PubMed

Radiation therapy

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Regimen

Study	Evidence	Comparator	Efficacy
Al-Sarraf et al. 1998 (Intergroup 0099)	Phase III	Cisplatin & RT -> CF	Inferior OS
Adelstein et al. 2003	Phase III	CF & RT	Seems not superior
Adelstein et al. 2003	Phase III	Cisplatin & RT	Seems to have inferior OS
Forastiere et al. 2003 (RTOG 91-11)	Phase III	CF -> RT	Seems to have inferior DFS
Forastiere et al. 2003 (RTOG 91-11)	Phase III	Cisplatin & RT	Inferior DFS
Denis et al. 2004 (GORTEC 94-01)	Phase III	Carboplatin, 5-FU, RT	Seems to have inferior OS
Chan et al. 2005	Phase III	Cisplatin & RT	Might have inferior OS
Bonner et al. 2006 (IMCL-9815)	Phase III	Cetuximab & RT	Seems to have inferior OS
Bourhis et al. 2012 (GORTEC 99-02)	Phase III	Carboplatin, 5-FU, RT	Seems to have inferior PFS
Bourhis et al. 2012 (GORTEC 99-02)	Phase III	Carboplatin, 5-FU, accelerated concurrent RT	Might have inferior PFS

Used as a comparator arm; included for reference purposes only.

References

Al-Sarraf M, LeBlanc M, Giri PG, Fu KK, Cooper J, Vuong T, Forastiere AA, Adams G, Sakr WA, Schuller DE, Ensley JF. Chemoradiotherapy versus radiotherapy in patients with advanced nasopharyngeal cancer: phase III randomized Intergroup study 0099. J Clin Oncol. 1998 Apr;16(4):1310-7. link to original article contains verified protocol PubMed
Adelstein DJ, Li Y, Adams GL, Wagner H Jr, Kish JA, Ensley JF, Schuller DE, Forastiere AA. 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 Jan 1;21(1):92-8. link to original article contains verified protocol PubMed
Forastiere AA, Goepfert H, Maor M, Pajak TF, Weber R, Morrison W, Glisson B, Trotti A, Ridge JA, Chao C, Peters G, Lee DJ, Leaf A, Ensley J, Cooper J. Concurrent chemotherapy and radiotherapy for organ preservation in advanced laryngeal cancer. N Engl J Med. 2003 Nov 27;349(22):2091-8. link to original article contains verified protocol PubMed
1. Update: Forastiere AA, Zhang Q, Weber RS, Maor MH, Goepfert H, Pajak TF, Morrison W, Glisson B, Trotti A, Ridge JA, Thorstad W, Wagner H, Ensley JF, Cooper JS. Long-term results of RTOG 91-11: a comparison of three nonsurgical treatment strategies to preserve the larynx in patients with locally advanced larynx cancer. J Clin Oncol. 2013 Mar 1;31(7):845-52. Epub 2012 Nov 26. link to original article contains partial protocol PubMed
Denis F, Garaud P, Bardet E, Alfonsi M, Sire C, Germain T, Bergerot P, Rhein B, Tortochaux J, Calais G. Final results of the 94-01 French Head and Neck Oncology and Radiotherapy Group randomized trial comparing radiotherapy alone with concomitant radiochemotherapy in advanced-stage oropharynx carcinoma. J Clin Oncol. 2004 Jan 1;22(1):69-76. Epub 2003 Dec 2. link to original article contains verified protocol PubMed
Chan AT, Leung SF, Ngan RK, Teo PM, Lau WH, Kwan WH, Hui EP, Yiu HY, Yeo W, Cheung FY, Yu KH, Chiu KW, Chan DT, Mok TS, Yau S, Yuen KT, Mo FK, Lai MM, Ma BB, Kam MK, Leung TW, Johnson PJ, Choi PH, Zee BC. Overall survival after concurrent cisplatin-radiotherapy compared with radiotherapy alone in locoregionally advanced nasopharyngeal carcinoma. J Natl Cancer Inst. 2005 Apr 6;97(7):536-9. link to original article contains verified protocol PubMed
Bonner JA, Harari PM, Giralt J, Azarnia N, Shin DM, Cohen RB, Jones CU, Sur R, Raben D, Jassem J, Ove R, Kies MS, Baselga J, Youssoufian H, Amellal N, Rowinsky EK, Ang KK. Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med. 2006 Feb 9;354(6):567-78. link to original article contains verified protocol PubMed
1. Update: Bonner JA, Harari PM, Giralt J, Cohen RB, Jones CU, Sur RK, Raben D, Baselga J, Spencer SA, Zhu J, Youssoufian H, Rowinsky EK, Ang KK. Radiotherapy plus cetuximab for locoregionally advanced head and neck cancer: 5-year survival data from a phase 3 randomised trial, and relation between cetuximab-induced rash and survival. Lancet Oncol. 2010 Jan;11(1):21-8. Epub 2009 Nov 10. link to original article contains partial protocol PubMed
2. QoL Analysis: Curran D, Giralt J, Harari PM, Ang KK, Cohen RB, Kies MS, Jassem J, Baselga J, Rowinsky EK, Amellal N, Comte S, Bonner JA. Quality of life in head and neck cancer patients after treatment with high-dose radiotherapy alone or in combination with cetuximab. J Clin Oncol. 2007 Jun 1;25(16):2191-7. link to original article contains partial protocol PubMed
3. Retrospective subgroup analysis: Rosenthal DI, Harari PM, Giralt J, Bell D, Raben D, Liu J, Schulten J, Ang KK, Bonner JA. Association of Human Papillomavirus and p16 Status With Outcomes in the IMCL-9815 Phase III Registration Trial for Patients With Locoregionally Advanced Oropharyngeal Squamous Cell Carcinoma of the Head and Neck Treated With Radiotherapy With or Without Cetuximab. J Clin Oncol. 2016 Apr 20;34(12):1300-8. Epub 2015 Dec 28. link to original article PubMed
Bourhis J, Sire C, Graff P, Grégoire V, Maingon P, Calais G, Gery B, Martin L, Alfonsi M, Desprez P, Pignon T, Bardet E, Rives M, Geoffrois L, Daly-Schveitzer N, Sen S, Tuchais C, Dupuis O, Guerif S, Lapeyre M, Favrel V, Hamoir M, Lusinchi A, Temam S, Pinna A, Tao YG, Blanchard P, Aupérin A. Concomitant chemoradiotherapy versus acceleration of radiotherapy with or without concomitant chemotherapy in locally advanced head and neck carcinoma (GORTEC 99-02): an open-label phase 3 randomised trial. Lancet Oncol. 2012 Feb;13(2):145-53. Epub 2012 Jan 18. link to original article contains verified protocol PubMed

TPF -> Carboplatin & RT

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DCF: Docetaxel, Cisplatin, Fluorouracil
TPF: Taxotere (Docetaxel), Platinol (Cisplatin), Fluorouracil
RT: Radiation Therapy

Regimen

Study	Evidence	Comparator	Efficacy
Posner et al. 2007 (TAX 324)	Phase III	CF -> Carboplatin & RT	Superior OS

Chemotherapy

Docetaxel (Taxotere) 75 mg/m² IV over 1 hour once on day 1, given first before cisplatin
Cisplatin (Platinol) 100 mg/m² IV over 30 to 180 minutes once on day 1, given second after docetaxel
Fluorouracil (5-FU) 1000 mg/m²/day IV continuous infusion over 96 hours on days 1 to 4, given third (total dose per cycle: 4000 mg/m²)

Supportive medications

Dexamethasone (Decadron) used (dose, route, schedule not specified) to prevent Docetaxel (Taxotere)-related side effects
Prophylactic antibiotics (further details not given) on days 5 to 14
Prophylactic granulocyte colony-stimulating factor not allowed

21-day cycle for 3 cycles; then start chemoradiotherapy 3 to 8 weeks after the start of cycle 3:

Chemoradiotherapy

Carboplatin (Paraplatin) AUC 1.5 IV over 1 hour once per day on days 1, 8, 15, 22, 29, 36, 43
Concurrent radiation therapy, 2 Gy fractions x 35 to 37 fractions (total dose: 70 to 74 Gy), given 5 times per week over 7 to 7.5 weeks

7 to 7.5-week course; surgery "performed 6 to 12 weeks after completion of chemoradiotherapy for patients who had an initial nodal stage of N2 and a partial response to induction chemotherapy, N3 disease, or residual disease after chemoradiotherapy."

References

Posner MR, Hershock DM, Blajman CR, Mickiewicz E, Winquist E, Gorbounova V, Tjulandin S, Shin DM, Cullen K, Ervin TJ, Murphy BA, Raez LE, Cohen RB, Spaulding M, Tishler RB, Roth B, Viroglio Rdel C, Venkatesan V, Romanov I, Agarwala S, Harter KW, Dugan M, Cmelak A, Markoe AM, Read PW, Steinbrenner L, Colevas AD, Norris CM Jr, Haddad RI; TAX 324 Study Group. Cisplatin and fluorouracil alone or with docetaxel in head and neck cancer. N Engl J Med. 2007 Oct 25;357(17):1705-15. link to original article contains verified protocol PubMed

TPF -> Cisplatin & RT

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DCF: Docetaxel, Cisplatin, Fluorouracil
TPF: Taxotere, Platinol, Fluorouracil
RT: Radiation Therapy

Regimen #1

Study	Evidence	Comparator	Efficacy
Sun et al. 2016	Phase III	Cisplatin & concurrent RT	Seems to have superior FFS

Chemotherapy

Docetaxel (Taxotere) 60 mg/m² IV once on day 1
Cisplatin (Platinol) 60 mg/m² IV once on day 1
Fluorouracil (5-FU) 600 mg/m²/day IV continuous infusion over 120 hours on days 1 to 5 (total dose per cycle: 3000 mg/m²)

21-day cycle for 3 cycles, followed by:

Chemoradiotherapy

Cisplatin (Platinol) 100 mg/m² IV once per day on days 1, 22, 43
Concurrent radiation therapy, see paper for details

One course

Regimen #2

Study	Evidence	Comparator	Efficacy
Lefebvre et al. 2013 (TREMPLIN)	Randomized Phase II	TPF -> Cetuximab & RT	Seems not superior

Chemotherapy

Docetaxel (Taxotere) 75 mg/m² IV once on day 1
Cisplatin (Platinol) 75 mg/m² IV once on day 1
Fluorouracil (5-FU) 750 mg/m² IV once per day on days 1 to 5 (total dose per cycle: 3750 mg/m²)

Supportive medications

"Hydration was delivered according to institutional protocols."
Dexamethasone (Decadron) 8 mg PO BID the day before, the day of, and day after Docetaxel (Taxotere)
Ciprofloxacin (Cipro) 500 mg PO BID on days 5 to 15
Prophylactic granulocyte colony-stimulating factor was not used. G-CSF 150 mcg/m² SC once per day was used if febrile neutropenia occurred.
"Setrons" (5-HT3 antagonists) given twice, before and after Cisplatin (Platinol)

21-day cycle for 3 cycles

Restaging of disease takes place 2 weeks after finishing cycle 3. Patients who had "at least 50% regression of their primary tumor volume and who recovered larynx mobility" were treated with Chemoradiotherapy. Patients who did not have at least 50% regression had salvage total laryngectomy.

Chemoradiotherapy

Cisplatin (Platinol) 100 mg/m² IV once per day on days 1, 22, 43
Concurrent radiation therapy, 2 Gy fractions x 35 fractions (total dose: 70 Gy), given once per day 5 times per week over 7 weeks

Regimen #3

Study	Evidence
Adelstein et al. 2010 (SWOG S0216)	Phase II

Chemotherapy

Docetaxel (Taxotere) 75 mg/m² IV once on day 1
Cisplatin (Platinol) 100 mg/m² IV once on day 1
Fluorouracil (5-FU) 1000 mg/m²/day IV continuous infusion over 4 days on days 1 to 4 (total dose per cycle: 4000 mg/m²)

Supportive medications

Ciprofloxacin (Cipro) prophylaxis for 10 days (dose/route/precise schedule not specified)
"Standard anti-emetics, hydration and diuresis"

21-day cycle for 2 cycles

Restaging of disease takes place 3 weeks after finishing cycle 2. Patients with stable or tumors which responded to therapy proceed to concurrent Chemoradiotherapy therapy. Patients with progressive disease are considered--if possible--for surgical resection and post-operative radiation. Patients who could not undergo surgery also received concurrent Chemoradiotherapy therapy.

Chemoradiotherapy

Cisplatin (Platinol) 100 mg/m² IV once per day on days 1 & 22
Concurrent radiation therapy, 1.8 Gy fractions x 30 fractions, given 5 times per week (total dose: 54 Gy)
- The last 12 treatments involved a boost volume, 1.5 Gy fractions x 12 fractions (dose to boost volume: 18 Gy)

Supportive medications

"Standard hydration and anti-emetic therapy"

6-week course; "Surgical resection was considered after concomitant chemoradiotherapy for those patients with histologically confirmed residual or recurrent disease at the primary site."

Regimen #4

Study	Evidence
Bae et al. 2010	Phase II

This study only involved patients with locoregionally advanced nasopharyngeal cancer.

Chemotherapy

Docetaxel (Taxotere) 70 mg/m² in 300 mL normal saline IV over 1 hour once on day 1, given first
Cisplatin (Platinol) 75 mg/m² IV over 3 hours once on day 1, given second
Fluorouracil (5-FU) 1000 mg/m²/day IV continuous infusion over 4 days on days 1 to 4, started after completion of cisplatin (total dose per cycle: 4000 mg/m²)

Supportive medications

Dexamethasone (Decadron) 20 mg IV once 30 minutes prior to Docetaxel (Taxotere)
Ranitidine (Zantac) 50 mg IV once 30 minutes prior to Docetaxel (Taxotere)
Chlorpheniramine (Chlor-Trimeton) 5 mg IV once 30 minutes prior to Docetaxel (Taxotere)
Posthydration after Cisplatin (Platinol) with normal saline (volume/rate not specified)
Ondansetron (Zofran) 8 mg IV "was routinely given"
Levofloxacin (Levaquin) 500 mg PO once per day on days 5 to 10 as prophylaxis
Prophylactic G-CSF per physician's discretion

21-day cycle for 3 cycles; then proceed to chemoradiotherapy:

Chemoradiotherapy

Cisplatin (Platinol) 100 mg/m² IV once per day on days 1 & 22
Concurrent radiation therapy, 1.8 to 2 Gy fractions (total dose: 68.4 Gy), given 5 times per week

References

Adelstein DJ, Moon J, Hanna E, Giri PG, Mills GM, Wolf GT, Urba SG. 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 Feb;32(2):221-8. link to PMC article contains verified protocol PubMed
Bae WK, Hwang JE, Shim HJ, Cho SH, Lee JK, Lim SC, Chung WK, Chung IJ. Phase II study of docetaxel, cisplatin, and 5-FU induction chemotherapy followed by chemoradiotherapy in locoregionally advanced nasopharyngeal cancer. Cancer Chemother Pharmacol. 2010 Feb;65(3):589-95. link to original article contains verified protocol PubMed
Lefebvre JL, Pointreau Y, Rolland F, Alfonsi M, Baudoux A, Sire C, de Raucourt D, Malard O, Degardin M, Tuchais C, Blot E, Rives M, Reyt E, Tourani JM, Geoffrois L, Peyrade F, Guichard F, Chevalier D, Babin E, Lang P, Janot F, Calais G, Garaud P, Bardet E. Induction chemotherapy followed by either chemoradiotherapy or bioradiotherapy for larynx preservation: the TREMPLIN randomized phase II study. J Clin Oncol. 2013 Mar 1;31(7):853-9. Epub 2013 Jan 22. link to original article contains verified protocol PubMed
Sun Y, Li WF, Chen NY, Zhang N, Hu GQ, Xie FY, Sun Y, Chen XZ, Li JG, Zhu XD, Hu CS, Xu XY, Chen YY, Hu WH, Guo L, Mo HY, Chen L, Mao YP, Sun R, Ai P, Liang SB, Long GX, Zheng BM, Feng XL, Gong XC, Li L, Shen CY, Xu JY, Guo Y, Chen YM, Zhang F, Lin L, Tang LL, Liu MZ, Ma J. Induction chemotherapy plus concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: a phase 3, multicentre, randomised controlled trial. Lancet Oncol. 2016 Sep 26. [Epub ahead of print] link to original article contains verified protocol PubMed

TPF -> RT

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DCF: Docetaxel, Cisplatin, Fluorouracil
TPF: Taxotere (Docetaxel), Platinol (Cisplatin), Fluorouracil
RT: Radiation Therapy

Regimen #1

Study	Evidence	Comparator	Efficacy
Vermorken et al. 2007 (EORTC 24971/TAX 323)	Phase III	CF -> RT	Seems to have superior OS

Chemotherapy

Docetaxel (Taxotere) 75 mg/m² IV over 1 hour once on day 1, given first before cisplatin
Cisplatin (Platinol) 75 mg/m² IV over 1 hour once on day 1, given second after docetaxel
Fluorouracil (5-FU) 750 mg/m²/day IV continuous infusion over 5 days on days 1 to 5 (total dose per cycle: 3750 mg/m²)

Supportive medications

Dexamethasone (Decadron) 8 mg PO for 6 doses (exact schedule not specified) starting the night before Docetaxel (Taxotere)
Ciprofloxacin (Cipro) 500 mg PO BID "or an alternative agent" on days 5 to 15 as prophylaxis
"Adequate antiemetic medications during chemotherapy"
Prophylactic granulocyte colony-stimulating factor only allowed for patients who had "febrile neutropenia or infection, a delay in recovery of the absolute neutrophil count at day 28, or grade 4 neutropenia persisting for 7 days or more."

21-day cycle for 4 cycles

Patients without progressive disease and who had recovery of marrow function, resolution of mucositis, and healed from any dental procedures started radiation therapy within 4 to 7 weeks of finishing chemotherapy:

Radiotherapy

Radiation therapy over 7 weeks with one of the following (further details not provided):
- Conventional fractionation, total dose 66 to 70 Gy
- Accelerated fractionation, total dose 70 Gy
- Hyperfractionated, total dose 74 Gy

Regimen #2

Study	Evidence	Comparator	Efficacy
Pointreau et al. 2009 (GORTEC)	Phase III	CF -> RT	Superior ORR

Chemotherapy

Docetaxel (Taxotere) 75 mg/m² IV over 1 hour once on day 1
Cisplatin (Platinol) 75 mg/m² IV over 1 hour once on day 1
Fluorouracil (5-FU) 750 mg/m²/day IV continuous infusion over 5 days on days 1 to 5 (total dose per cycle: 3750 mg/m²)

Supportive medications

Normal saline (use of mannitol, KCl, and magnesium sulfate per institutional protocol) 1000 mL IV given twice, before and after Cisplatin (Platinol)
Dexamethasone (Decadron) 8 mg PO once per day the day before, the day of, and day after Docetaxel (Taxotere)
Ciprofloxacin (Cipro) 1000 mg PO (frequency not specified) on days 5 to 15
Prophylactic granulocyte colony-stimulating factor not used

21-day cycle for 3 cycles

Patients who responded to induction chemotherapy proceeded to radiation therapy within 3 to 7 weeks of finishing chemotherapy. Patients who did not respond to induction chemotherapy proceeded to surgery and postoperative radiotherapy (see Pointreau et al. 2009 for details).

Radiotherapy

Radiation therapy to the primary tumor and involved lymph nodes, 2 Gy fractions x 35 fractions (total dose: 70 Gy), given 5 times per week over 7 weeks. Prophylactic radiation to the volume at risk for microscopic disease, 2 Gy fractions x 25 to 27 fractions (total dose: 50 to 54 Gy), given 5 times per week.
"Chemotherapy (cisplatin, carboplatin, and 5-fluorouracil or a combination of two drugs) during radiotherapy was allowed for all patients who were treated at the same institute, according to its practice." No further details available.

References

Vermorken JB, Remenar E, van Herpen C, Gorlia T, Mesia R, Degardin M, Stewart JS, Jelic S, Betka J, Preiss JH, van den Weyngaert D, Awada A, Cupissol D, Kienzer HR, Rey A, Desaunois I, Bernier J, Lefebvre JL; EORTC 24971/TAX 323 Study Group. Cisplatin, fluorouracil, and docetaxel in unresectable head and neck cancer. N Engl J Med. 2007 Oct 25;357(17):1695-704. link to original article contains verified protocol PubMed
1. QoL Analysis: van Herpen CM, Mauer ME, Mesia R, Degardin M, Jelic S, Coens C, Betka J, Bernier J, Remenar E, Stewart JS, Preiss JH, van den Weyngaert D, Bottomley A, Vermorken JB; EORTC Head and Neck Group. Short-term health-related quality of life and symptom control with docetaxel, cisplatin, 5-fluorouracil and cisplatin (TPF), 5-fluorouracil (PF) for induction in unresectable locoregionally advanced head and neck cancer patients (EORTC 24971/TAX 323). Br J Cancer. 2010 Oct 12;103(8):1173-81. Epub 2010 Sep 14. link to original article contains verified protocol PubMed
Pointreau Y, Garaud P, Chapet S, Sire C, Tuchais C, Tortochaux J, Faivre S, Guerrif S, Alfonsi M, Calais G. Randomized trial of induction chemotherapy with cisplatin and 5-fluorouracil with or without docetaxel for larynx preservation. J Natl Cancer Inst. 2009 Apr 1;101(7):498-506. Epub 2009 Mar 24. link to original article contains verified protocol PubMed content property of HemOnc.org

Recurrent or metastatic disease

Afatinib (Gliotrif)

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Regimen

Study	Evidence	Comparator	Efficacy
Machiels et al. 2015 (LUX-Head & Neck 1)	Phase III	Methotrexate	Seems to have superior PFS

Chemotherapy

Afatinib (Gliotrif) 40 mg PO once per day

References

Machiels JP, Haddad RI, Fayette J, Licitra LF, Tahara M, Vermorken JB, Clement PM, Gauler T, Cupissol D, Grau JJ, Guigay J, Caponigro F, de Castro G Jr, de Souza Viana L, Keilholz U, Del Campo JM, Cong XJ, Ehrnrooth E, Cohen EE; LUX-H&N 1 investigators. 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 May;16(5):583-94. Epub 2015 Apr 16. link to original article contains protocol PubMed

Carboplatin & Docetaxel

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Regimen

Study	Evidence
Samlowski et al. 2007	Phase II

Chemotherapy

Carboplatin (Paraplatin) AUC 6 IV once on day 1
Docetaxel (Taxotere) 65 mg/m² IV once on day 1

21-day cycles

References

Samlowski WE, Moon J, Kuebler JP, Nichols CR, Gandara DR, Ozer H, Williamson SK, Atkins JN, Schuller DE, Ensley JF. 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 Apr-May;25(3):182-8. link to original article contains protocol PubMed

Carboplatin & Fluorouracil

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Regimen

Study	Evidence	Comparator	Efficacy
Forastiere et al. 1992	Phase III	CF	Not reported
Forastiere et al. 1992	Phase III	MTX	Seems to have superior ORR
Vermorken et al. 2008	Phase III	Carboplatin, Fluorouracil, Cetuximab	Seems to have inferior OS

Chemotherapy

Carboplatin (Paraplatin) 300 mg/m² IV over 5 to 10 minutes once on day 1
Fluorouracil (5-FU) 1000 mg/m²/day IV continuous infusion over 96 hours, start day not specified (total dose per cycle: 4000 mg/m²)

Supportive medications

"Standard antiemetic regimens"

28-day cycles

References

Forastiere AA, Metch B, Schuller DE, Ensley JF, Hutchins LF, Triozzi P, Kish JA, McClure S, VonFeldt E, Williamson SK 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 Aug;10(8):1245-51. link to original article contains verified protocol PubMed
Vermorken JB, Mesia R, Rivera F, Remenar E, Kawecki A, Rottey S, Erfan J, Zabolotnyy D, Kienzer HR, Cupissol D, Peyrade F, Benasso M, Vynnychenko I, De Raucourt D, Bokemeyer C, Schueler A, Amellal N, Hitt R. Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med. 2008 Sep 11;359(11):1116-27. link to original article contains verified protocol PubMed

Carboplatin, Fluorouracil, Cetuximab

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Regimen

Study	Evidence	Comparator	Efficacy
Vermorken et al. 2008	Phase III	Carboplatin & Fluorouracil	Seems to have superior OS

Chemotherapy

Carboplatin (Paraplatin) AUC 5 IV over 1 hour once on day 1
Fluorouracil (5-FU) 1000 mg/m²/day IV continuous infusion over 4 days on days 1 to 4 (total dose per cycle: 4000 mg/m²)
Cetuximab (Erbitux) given first before chemotherapy and ending at least 1 hour before chemotherapy starts, as follows:
- Cycle 1: 400 mg/m² IV over 2 hours once on day 1, then 250 mg/m² IV over 1 hour once per day on days 8 & 15
- Cycle 2 onwards: 250 mg/m² IV over 1 hour once per day on days 1, 8, 15

21-day cycle for up to 6 cycles

References

Vermorken JB, Mesia R, Rivera F, Remenar E, Kawecki A, Rottey S, Erfan J, Zabolotnyy D, Kienzer HR, Cupissol D, Peyrade F, Benasso M, Vynnychenko I, De Raucourt D, Bokemeyer C, Schueler A, Amellal N, Hitt R. Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med. 2008 Sep 11;359(11):1116-27. link to original article contains verified protocol PubMed

Cetuximab (Erbitux)

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Regimen

Study	Evidence
Vermorken et al. 2007	Phase II

Chemotherapy

Cetuximab (Erbitux) 400 mg/m² (includes cetuximab 20 mg IV once as a test dose) IV over 120 minutes once on day 1; then starting 1 week later, Cetuximab (Erbitux) 250 mg/m² IV over 1 hour once per week

References

Vermorken JB, Trigo J, Hitt R, Koralewski P, Diaz-Rubio E, Rolland F, Knecht R, Amellal N, Schueler A, Baselga J. 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 Jun 1;25(16):2171-7. link to original article contains verified protocol PubMed

CF

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CF: Cisplatin and Fluorouracil

Regimen #1

Study	Evidence	Comparator	Efficacy
Zhang et al. 2016	Phase III	Cisplatin & Gemcitabine	Inferior PFS

Note: this regimen was intended for recurrent or metastatic nasopharyngeal carcinoma.

Chemotherapy

Cisplatin (Platinol) 80 mg/m² IV once on day 1
Fluorouracil (5-FU) 1000 mg/m²/day IV continuous infusion on days 1 to 4 (total dose per cycle: 4000 mg/m²)

21-day cycle for up to 6 cycles

Regimen #2

Study	Evidence	Comparator	Efficacy
Forastiere et al. 1992	Phase III	Carboplatin & Fluorouracil	Not reported
Forastiere et al. 1992	Phase III	MTX	Superior ORR
Gibson et al. 2005 (ECOG E1395)	Phase III	CP	Seems not superior
Vermorken et al. 2008	Phase III	Cisplatin, Fluorouracil, Cetuximab	Seems to have inferior OS
Vermorken et al. 2013 (SPECTRUM)	Phase III	Cisplatin, Fluorouracil, Panitumumab	Inferior PFS

Chemotherapy

Cisplatin (Platinol) 100 mg/m² IV once on day 1
- ECOG E1395: Carboplatin (Paraplatin) AUC 6 IV once on day 1 could be substituted in patients who developed at least grade 2 neuropathy or renal impairment (creatinine clearance <50 mL/min; note: later in Gibson et al. 2005, it says that carboplatin was used for patients who had creatinine clearance ≤50 mL/min)
Fluorouracil (5-FU) 1000 mg/m²/day IV continuous infusion on days 1 to 4 (total dose per cycle: 4000 mg/m²)

Supportive medications

Details vary per reference
Pretreatment and posttreatment hydration and mannitol diuresis with Cisplatin (Platinol)
"Standard antiemetic regimens"

21-day cycle for up to 6 cycles (SPECTRUM) or indefinitely, see note below

In ECOG E1395, patients with complete response (CR) received at least 6 cycles or 2 cycles past the point at which CR was documented, whichever came later; patients with partial response (PR) continued on treatment until there was evidence of CR or progression disease; patients with stable disease (SD) could discontinue treatment after six cycles.

References

Forastiere AA, Metch B, Schuller DE, Ensley JF, Hutchins LF, Triozzi P, Kish JA, McClure S, VonFeldt E, Williamson SK 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 Aug;10(8):1245-51. link to original article contains verified protocol PubMed
Gibson MK, Li Y, Murphy B, Hussain MH, DeConti RC, Ensley J, Forastiere AA; Eastern Cooperative Oncology Group. 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 May 20;23(15):3562-7. link to original article contains verified protocol PubMed
Vermorken JB, Mesia R, Rivera F, Remenar E, Kawecki A, Rottey S, Erfan J, Zabolotnyy D, Kienzer HR, Cupissol D, Peyrade F, Benasso M, Vynnychenko I, De Raucourt D, Bokemeyer C, Schueler A, Amellal N, Hitt R. Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med. 2008 Sep 11;359(11):1116-27. link to original article contains verified protocol PubMed
Vermorken JB, Stöhlmacher-Williams J, Davidenko I, Licitra L, Winquist E, Villanueva C, Foa P, Rottey S, Skladowski K, Tahara M, Pai VR, Faivre S, Blajman CR, Forastiere AA, Stein BN, Oliner KS, Pan Z, Bach BA; SPECTRUM investigators. Cisplatin and fluorouracil with or without panitumumab in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck (SPECTRUM): an open-label phase 3 randomised trial. Lancet Oncol. 2013 Jul;14(8):697-710. Epub 2013 Jun 6. link to original article contains protocol PubMed
Zhang L, Huang Y, Hong S, Yang Y, Yu G, Jia J, Peng P, Wu X, Lin Q, Xi X, Peng J, Xu M, Chen D, Lu X, Wang R, Cao X, Chen X, Lin Z, Xiong J, Lin Q, Xie C, Li Z, Pan J, Li J, Wu S, Lian Y, Yang Q, Zhao C. Gemcitabine plus cisplatin versus fluorouracil plus cisplatin in recurrent or metastatic nasopharyngeal carcinoma:a multicentre, randomised, open-label, phase 3 trial. Lancet. 2016 Aug 23. [Epub ahead of print] link to original article contains protocol PubMed

Cisplatin (Platinol)

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Regimen

Study	Evidence	Comparator	Efficacy
Burtness et al. 2005	Phase III	Cisplatin & Cetuximab	Seems not superior

Chemotherapy

Cisplatin (Platinol) 100 mg/m² IV once on day 1

28-day cycles

Per physician discretion, patients with complete response (CR) could have treatment discontinued 2 cycles past the point at which CR was attained. Patients with partial response (PR) continued on treatment until there was evidence of CR or progression disease. Patients with stable disease (SD) could discontinue treatment after 6 cycles. Patients with progressive disease discontinued therapy.

References

Burtness B, Goldwasser MA, Flood W, Mattar B, Forastiere AA; Eastern Cooperative Oncology Group. 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 Dec 1;23(34):8646-54. link to original article contains verified protocol PubMed

Cisplatin & Cetuximab

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Regimen

Study	Evidence	Comparator	Efficacy
Burtness et al. 2005	Phase III	Cisplatin	Seems not superior

Chemotherapy

Cisplatin (Platinol) 100 mg/m² IV once on day 1
Cetuximab (Erbitux) as follows:
- Cycle 1: 200 mg/m² IV over 120 minutes once on day 1, then 125 mg/m² IV over 60 minutes once per day on days 8, 15, 22
- Subsequent cycles: 125 mg/m² IV over 60 minutes once per day on days 1, 8, 15, 22

28-day cycles

Per physician discretion, patients with complete response (CR) could have treatment discontinued 2 cycles past the point at which CR was attained. Patients with partial response (PR) continued on treatment until there was evidence of CR or progression disease. Patients with stable disease (SD) could discontinue treatment after 6 cycles. Patients with progressive disease discontinued therapy.

References

Burtness B, Goldwasser MA, Flood W, Mattar B, Forastiere AA; Eastern Cooperative Oncology Group. 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 Dec 1;23(34):8646-54. link to original article contains verified protocol PubMed

Cisplatin, Fluorouracil, Cetuximab

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Regimen

Study	Evidence	Comparator	Efficacy
Vermorken et al. 2008	Phase III	CF	Seems to have superior OS

Chemotherapy

Cisplatin (Platinol) 100 mg/m² IV over 1 hour once on day 1
Fluorouracil (5-FU) 1000 mg/m²/day IV continuous infusion over 4 days on days 1 to 4 (total dose per cycle: 4000 mg/m²)
Cetuximab (Erbitux) given first before chemotherapy and ending at least 1 hour before chemotherapy starts, as follows:
- Cycle 1: 400 mg/m² IV over 2 hours once on day 1, then 250 mg/m² IV over 1 hour once per day on days 8 & 15
- Cycle 2 onwards: 250 mg/m² IV over 1 hour once per day on days 1, 8, 15

21-day cycle for up to 6 cycles

References

Vermorken JB, Mesia R, Rivera F, Remenar E, Kawecki A, Rottey S, Erfan J, Zabolotnyy D, Kienzer HR, Cupissol D, Peyrade F, Benasso M, Vynnychenko I, De Raucourt D, Bokemeyer C, Schueler A, Amellal N, Hitt R. Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med. 2008 Sep 11;359(11):1116-27. link to original article contains verified protocol PubMed

Cisplatin, Fluorouracil, Panitumumab

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Regimen

Study	Evidence	Comparator	Efficacy
Vermorken et al. 2013 (SPECTRUM)	Phase III	CF	Superior PFS

Chemotherapy

Cisplatin (Platinol) 100 mg/m² IV once on day 1
Fluorouracil (5-FU) 1000 mg/m²/day IV continuous infusion on days 1 to 4 (total dose per cycle: 4000 mg/m²)
Panitumumab (Vectibix) 9 mg/kg IV once on day 1

21-day cycle for up to 6 cycles

Patients could choose to continue panitumumab maintenance.

References

Vermorken JB, Stöhlmacher-Williams J, Davidenko I, Licitra L, Winquist E, Villanueva C, Foa P, Rottey S, Skladowski K, Tahara M, Pai VR, Faivre S, Blajman CR, Forastiere AA, Stein BN, Oliner KS, Pan Z, Bach BA; SPECTRUM investigators. Cisplatin and fluorouracil with or without panitumumab in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck (SPECTRUM): an open-label phase 3 randomised trial. Lancet Oncol. 2013 Jul;14(8):697-710. Epub 2013 Jun 6. link to original article contains protocol PubMed

Cisplatin & Gemcitabine

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Regimen

Study	Evidence	Comparator	Efficacy
Zhang et al. 2016	Phase III	CF	Superior PFS

Note: this regimen was intended for recurrent or metastatic nasopharyngeal carcinoma.

Chemotherapy

Cisplatin (Platinol) 80 mg/m² IV once on day 1
Gemcitabine (Gemzar) 1000 mg/m²/day IV once per day on days 1 & 8

21-day cycle for up to 6 cycles

References

Zhang L, Huang Y, Hong S, Yang Y, Yu G, Jia J, Peng P, Wu X, Lin Q, Xi X, Peng J, Xu M, Chen D, Lu X, Wang R, Cao X, Chen X, Lin Z, Xiong J, Lin Q, Xie C, Li Z, Pan J, Li J, Wu S, Lian Y, Yang Q, Zhao C. Gemcitabine plus cisplatin versus fluorouracil plus cisplatin in recurrent or metastatic nasopharyngeal carcinoma:a multicentre, randomised, open-label, phase 3 trial. Lancet. 2016 Aug 23. [Epub ahead of print] link to original article contains protocol PubMed

CP

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CP: Cisplatin and Paclitaxel

Regimen

Study	Evidence	Comparator	Efficacy
Gibson et al. 2005 (ECOG E1395)	Phase III	CF	Seems not superior

Chemotherapy

Cisplatin (Platinol) 75 mg/m² IV once on day 1
- Carboplatin (Paraplatin) AUC 6 IV once on day 1 could be used in patients who developed at least grade 2 neuropathy or renal impairment (creatinine clearance <50 mL/min; note: later in Gibson et al. 2005, it says that carboplatin was used for patients who had creatinine clearance ≤50 mL/min)
Paclitaxel (Taxol) 175 mg/m² IV over 3 hours once on day 1

Supportive medications

Hydration and forced diuresis (no further details given) with Cisplatin (Platinol)
Dexamethasone (Decadron) 20 mg PO given twice, 12 and 6 hours prior to Paclitaxel (Taxol)
Diphenhydramine (Benadryl) (no dose specified) IV within 60 minutes prior to Paclitaxel (Taxol)
H2 receptor antagonist (no further details given) IV within 60 minutes prior to Paclitaxel (Taxol)

21-day cycles

Patients with complete response (CR) received at least 6 cycles or 2 cycles past the point at which CR was documented, whichever came later. Patients with partial response (PR) continued on treatment until there was evidence of CR or progression disease. "Patients with stable disease (SD) could discontinue treatment after six cycles."

References

Gibson MK, Li Y, Murphy B, Hussain MH, DeConti RC, Ensley J, Forastiere AA; Eastern Cooperative Oncology Group. 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 May 20;23(15):3562-7. link to original article contains verified protocol PubMed

Gemcitabine (Gemzar)

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Regimen

Study	Evidence
Zhang et al. 2008	Phase II

This study only involved patients with advanced (stage IV) or metastatic nasopharyngeal cancer who had already received previous platinum-based chemotherapy.

Chemotherapy

Gemcitabine (Gemzar) 1000 mg/m² in 100 mL normal saline IV over 30 minutes once per day on days 1, 8, 15

Supportive medications

5-HT3 receptor antagonists prior to chemotherapy
G-CSF and GM-CSF were not used

28-day cycles, given until progression of disease

References

Zhang L, Zhang Y, Huang PY, Xu F, Peng PJ, Guan ZZ. 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 Jan;61(1):33-8. Epub 2007 Mar 20. link to original article contains verified protocol PubMed

Methotrexate (MTX)

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Regimen

Study	Evidence	Comparator	Efficacy
Forastiere et al. 1992	Phase III	Carboplatin & Fluorouracil	Seems to have inferior ORR
Forastiere et al. 1992	Phase III	CF	Inferior ORR
Machiels et al. 2015 (LUX-Head & Neck 1)	Phase III	Afatinib	Seems to have inferior PFS

Chemotherapy

Methotrexate (MTX) 40 mg/m² IV once per week

Supportive medications

"Standard antiemetic regimens"

References

Forastiere AA, Metch B, Schuller DE, Ensley JF, Hutchins LF, Triozzi P, Kish JA, McClure S, VonFeldt E, Williamson SK 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 Aug;10(8):1245-51. link to original article contains verified protocol PubMed
Machiels JP, Haddad RI, Fayette J, Licitra LF, Tahara M, Vermorken JB, Clement PM, Gauler T, Cupissol D, Grau JJ, Guigay J, Caponigro F, de Castro G Jr, de Souza Viana L, Keilholz U, Del Campo JM, Cong XJ, Ehrnrooth E, Cohen EE; LUX-H&N 1 investigators. 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 May;16(5):583-94. Epub 2015 Apr 16. link to original article contains protocol PubMed

Pembrolizumab (Keytruda)

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Regimen

Study	Evidence
Seiwert et al. 2016 (KEYNOTE-012)	Phase Ib, >20 pts

Immunotherapy

Pembrolizumab (Keytruda) 10 mg/kg IV once on day 1

2-week cycles until progression, intolerance, or maximum of 24 months

References

Seiwert TY, Burtness B, Mehra R, Weiss J, Berger R, Eder JP, Heath K, McClanahan T, Lunceford J, Gause C, Cheng JD, Chow LQ. 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 Jul;17(7):956-65. Epub 2016 May 27. link to original article contains verified protocol PubMed

@@ Line 11: / Line 11: @@
 =Adjuvant chemotherapy & radiation therapy=
-==Cisplatin & concurrent RT {{#subobject:90d8d0|Regimen=1}}==
+==Cisplatin & RT {{#subobject:90d8d0|Regimen=1}}==
 {| class="wikitable" style="float:right; margin-left: 5px;"
 |-
 |[[#top|back to top]]
 |}
+<br>RT: '''<u>R</u>'''adiation '''<u>T</u>'''herapy
 ===Regimen #1 {{#subobject:21d2ff|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
@@ Line 22: / Line 22: @@
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
 |[http://www.nejm.org/doi/full/10.1056/NEJMoa032646 Cooper et al. 2004 (RTOG 9501, ECOG R9501, SWOG 9515)]
 |style="background-color:#00CD00"|Phase III
 |[[Head_and_neck_cancer#Radiation_therapy|Radiation therapy]]
+|style="background-color:#00CD00"|Seems to have superior DFS
 |-
 |}
@@ Line 46: / Line 48: @@
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
 |[http://www.nejm.org/doi/full/10.1056/NEJMoa032641 Bernier et al. 2004 (EORTC 22931)]
 |style="background-color:#00CD00"|Phase III
 |[[Head_and_neck_cancer#Radiation_therapy|Radiation therapy]]
+|style="background-color:#00CD00"|Seems to have superior OS
 |-
 |}
@@ Line 66: / Line 70: @@
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
 |[http://www.redjournal.org/article/0360-3016(91)90098-O/abstract Bachaud et al. 1991]
 |style="background-color:#00CD00"|Phase III
 |[[Head_and_neck_cancer#Radiation_therapy|Radiation therapy]]
+|style="background-color:#00CD00"|Superior OS
 |-
 |}
@@ Line 77: / Line 83: @@
 ====Supportive medications====
-*"Forced hydration" with cisplatin
+*"Forced hydration" with [[Cisplatin (Platinol)]]
 '''7 to 9-week course, depending on duration of radiation therapy'''
 ===References===
-# Bachaud JM, David JM, Boussin G, Daly N. Combined postoperative radiotherapy and weekly cisplatin infusion for locally advanced squamous cell carcinoma of the head and neck: preliminary report of a randomized trial. Int J Radiat Oncol Biol Phys. 1991 Feb;20(2):243-6. [http://www.redjournal.org/article/0360-3016(91)90098-O/abstract link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/1991685 PubMed]
+# Bachaud JM, David JM, Boussin G, Daly N. Combined postoperative radiotherapy and weekly cisplatin infusion for locally advanced squamous cell carcinoma of the head and neck: preliminary report of a randomized trial. Int J Radiat Oncol Biol Phys. 1991 Feb;20(2):243-6. [http://www.redjournal.org/article/0360-3016(91)90098-O/abstract link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/1991685 PubMed]
-## '''Update:''' Bachaud JM, Cohen-Jonathan E, Alzieu C, David JM, Serrano E, Daly-Schveitzer N. Combined postoperative radiotherapy and weekly cisplatin infusion for locally advanced head and neck carcinoma: final report of a randomized trial. Int J Radiat Oncol Biol Phys. 1996 Dec 1;36(5):999-1004. [http://www.redjournal.org/article/S0360-3016%2896%2900430-0/abstract link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/8985019 PubMed]
+## '''Update:''' Bachaud JM, Cohen-Jonathan E, Alzieu C, David JM, Serrano E, Daly-Schveitzer N. Combined postoperative radiotherapy and weekly cisplatin infusion for locally advanced head and neck carcinoma: final report of a randomized trial. Int J Radiat Oncol Biol Phys. 1996 Dec 1;36(5):999-1004. [http://www.redjournal.org/article/S0360-3016%2896%2900430-0/abstract link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/8985019 PubMed]
-# Cooper JS, Pajak TF, Forastiere AA, Jacobs J, Campbell BH, Saxman SB, Kish JA, Kim HE, Cmelak AJ, Rotman M, Machtay M, Ensley JF, Chao KS, Schultz CJ, Lee N, Fu KK; Radiation Therapy Oncology Group 9501/Intergroup. Postoperative concurrent radiotherapy and chemotherapy for high-risk squamous-cell carcinoma of the head and neck. N Engl J Med. 2004 May 6;350(19):1937-44. [http://www.nejm.org/doi/full/10.1056/NEJMoa032646 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/15128893 PubMed]
+# Cooper JS, Pajak TF, Forastiere AA, Jacobs J, Campbell BH, Saxman SB, Kish JA, Kim HE, Cmelak AJ, Rotman M, Machtay M, Ensley JF, Chao KS, Schultz CJ, Lee N, Fu KK; Radiation Therapy Oncology Group 9501/Intergroup. Postoperative concurrent radiotherapy and chemotherapy for high-risk squamous-cell carcinoma of the head and neck. N Engl J Med. 2004 May 6;350(19):1937-44. [http://www.nejm.org/doi/full/10.1056/NEJMoa032646 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/15128893 PubMed]
-## '''Update:''' Cooper JS, Zhang Q, Pajak TF, Forastiere AA, Jacobs J, Saxman SB, Kish JA, Kim HE, Cmelak AJ, Rotman M, Lustig R, Ensley JF, Thorstad W, Schultz CJ, Yom SS, Ang KK. Long-term follow-up of the RTOG 9501/intergroup phase III trial: postoperative concurrent radiation therapy and chemotherapy in high-risk squamous cell carcinoma of the head and neck. Int J Radiat Oncol Biol Phys. 2012 Dec 1;84(5):1198-205. Epub 2012 Jun 30. [http://www.redjournal.org/article/S0360-3016%2812%2900650-5/abstract link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22749632 PubMed]
+## '''Update:''' Cooper JS, Zhang Q, Pajak TF, Forastiere AA, Jacobs J, Saxman SB, Kish JA, Kim HE, Cmelak AJ, Rotman M, Lustig R, Ensley JF, Thorstad W, Schultz CJ, Yom SS, Ang KK. Long-term follow-up of the RTOG 9501/intergroup phase III trial: postoperative concurrent radiation therapy and chemotherapy in high-risk squamous cell carcinoma of the head and neck. Int J Radiat Oncol Biol Phys. 2012 Dec 1;84(5):1198-205. Epub 2012 Jun 30. [http://www.redjournal.org/article/S0360-3016%2812%2900650-5/abstract link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22749632 PubMed]
-# Bernier J, Domenge C, Ozsahin M, Matuszewska K, Lefèbvre JL, Greiner RH, Giralt J, Maingon P, Rolland F, Bolla M, Cognetti F, Bourhis J, Kirkpatrick A, van Glabbeke M; European Organization for Research and Treatment of Cancer Trial 22931. Postoperative irradiation with or without concomitant chemotherapy for locally advanced head and neck cancer. N Engl J Med. 2004 May 6;350(19):1945-52. [http://www.nejm.org/doi/full/10.1056/NEJMoa032641 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/15128894 PubMed]
+# Bernier J, Domenge C, Ozsahin M, Matuszewska K, Lefèbvre JL, Greiner RH, Giralt J, Maingon P, Rolland F, Bolla M, Cognetti F, Bourhis J, Kirkpatrick A, van Glabbeke M; European Organization for Research and Treatment of Cancer Trial 22931. Postoperative irradiation with or without concomitant chemotherapy for locally advanced head and neck cancer. N Engl J Med. 2004 May 6;350(19):1945-52. [http://www.nejm.org/doi/full/10.1056/NEJMoa032641 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/15128894 PubMed]
-# '''Posthoc analysis:''' Bernier J, Cooper JS, Pajak TF, van Glabbeke M, Bourhis J, Forastiere A, Ozsahin EM, Jacobs JR, Jassem J, Ang KK, Lefèbvre JL. Defining risk levels in locally advanced head and neck cancers: a comparative analysis of concurrent postoperative radiation plus chemotherapy trials of the EORTC (#22931) and RTOG (# 9501). Head Neck. 2005 Oct;27(10):843-50. [http://onlinelibrary.wiley.com/doi/10.1002/hed.20279/full link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/16161069 PubMed]
+# '''Posthoc analysis:''' Bernier J, Cooper JS, Pajak TF, van Glabbeke M, Bourhis J, Forastiere A, Ozsahin EM, Jacobs JR, Jassem J, Ang KK, Lefèbvre JL. Defining risk levels in locally advanced head and neck cancers: a comparative analysis of concurrent postoperative radiation plus chemotherapy trials of the EORTC (#22931) and RTOG (# 9501). Head Neck. 2005 Oct;27(10):843-50. [http://onlinelibrary.wiley.com/doi/10.1002/hed.20279/full link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/16161069 PubMed]
 ==Radiation therapy {{#subobject:571927|Regimen=1}}==
@@ Line 100: / Line 106: @@
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
 |[http://www.redjournal.org/article/0360-3016(91)90098-O/abstract Bachaud et al. 1991]
 |style="background-color:#00CD00"|Phase III
-|[[Head_and_neck_cancer#Cisplatin_.26_concurrent_RT|Cisplatin & RT]]
+|[[Head_and_neck_cancer#Cisplatin_.26_RT|Cisplatin & RT]]
+|style="background-color:#ff0000"|Inferior OS
 |-
 |[http://www.nejm.org/doi/full/10.1056/NEJMoa032646 Cooper et al. 2004 (RTOG 9501, ECOG R9501, SWOG 9515)]
 |style="background-color:#00CD00"|Phase III
-|[[Head_and_neck_cancer#Cisplatin_.26_concurrent_RT|Cisplatin & RT]]
+|[[Head_and_neck_cancer#Cisplatin_.26_RT|Cisplatin & RT]]
+|style="background-color:#ff0000"|Seems to have inferior DFS
 |-
 |[http://www.nejm.org/doi/full/10.1056/NEJMoa032641 Bernier et al. 2004 (EORTC 22931)]
 |style="background-color:#00CD00"|Phase III
-|[[Head_and_neck_cancer#Cisplatin_.26_concurrent_RT|Cisplatin & RT]]
+|[[Head_and_neck_cancer#Cisplatin_.26_RT|Cisplatin & RT]]
+|style="background-color:#ff0000"|Seems to have inferior OS
 |-
 |}
@@ Line 118: / Line 128: @@
 ===References===
-# Bachaud JM, David JM, Boussin G, Daly N. Combined postoperative radiotherapy and weekly cisplatin infusion for locally advanced squamous cell carcinoma of the head and neck: preliminary report of a randomized trial. Int J Radiat Oncol Biol Phys. 1991 Feb;20(2):243-6. [http://www.redjournal.org/article/0360-3016(91)90098-O/abstract link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/1991685 PubMed]
+# Bachaud JM, David JM, Boussin G, Daly N. Combined postoperative radiotherapy and weekly cisplatin infusion for locally advanced squamous cell carcinoma of the head and neck: preliminary report of a randomized trial. Int J Radiat Oncol Biol Phys. 1991 Feb;20(2):243-6. [http://www.redjournal.org/article/0360-3016(91)90098-O/abstract link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/1991685 PubMed]
-## '''Update:''' Bachaud JM, Cohen-Jonathan E, Alzieu C, David JM, Serrano E, Daly-Schveitzer N. Combined postoperative radiotherapy and weekly cisplatin infusion for locally advanced head and neck carcinoma: final report of a randomized trial. Int J Radiat Oncol Biol Phys. 1996 Dec 1;36(5):999-1004. [http://www.redjournal.org/article/S0360-3016%2896%2900430-0/abstract link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/8985019 PubMed]
+## '''Update:''' Bachaud JM, Cohen-Jonathan E, Alzieu C, David JM, Serrano E, Daly-Schveitzer N. Combined postoperative radiotherapy and weekly cisplatin infusion for locally advanced head and neck carcinoma: final report of a randomized trial. Int J Radiat Oncol Biol Phys. 1996 Dec 1;36(5):999-1004. [http://www.redjournal.org/article/S0360-3016%2896%2900430-0/abstract link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/8985019 PubMed]
-# Cooper JS, Pajak TF, Forastiere AA, Jacobs J, Campbell BH, Saxman SB, Kish JA, Kim HE, Cmelak AJ, Rotman M, Machtay M, Ensley JF, Chao KS, Schultz CJ, Lee N, Fu KK; Radiation Therapy Oncology Group 9501/Intergroup. Postoperative concurrent radiotherapy and chemotherapy for high-risk squamous-cell carcinoma of the head and neck. N Engl J Med. 2004 May 6;350(19):1937-44. [http://www.nejm.org/doi/full/10.1056/NEJMoa032646 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/15128893 PubMed]
+# Cooper JS, Pajak TF, Forastiere AA, Jacobs J, Campbell BH, Saxman SB, Kish JA, Kim HE, Cmelak AJ, Rotman M, Machtay M, Ensley JF, Chao KS, Schultz CJ, Lee N, Fu KK; Radiation Therapy Oncology Group 9501/Intergroup. Postoperative concurrent radiotherapy and chemotherapy for high-risk squamous-cell carcinoma of the head and neck. N Engl J Med. 2004 May 6;350(19):1937-44. [http://www.nejm.org/doi/full/10.1056/NEJMoa032646 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/15128893 PubMed]
-## '''Update:''' Cooper JS, Zhang Q, Pajak TF, Forastiere AA, Jacobs J, Saxman SB, Kish JA, Kim HE, Cmelak AJ, Rotman M, Lustig R, Ensley JF, Thorstad W, Schultz CJ, Yom SS, Ang KK. Long-term follow-up of the RTOG 9501/intergroup phase III trial: postoperative concurrent radiation therapy and chemotherapy in high-risk squamous cell carcinoma of the head and neck. Int J Radiat Oncol Biol Phys. 2012 Dec 1;84(5):1198-205. Epub 2012 Jun 30. [http://www.redjournal.org/article/S0360-3016%2812%2900650-5/abstract link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22749632 PubMed]
+## '''Update:''' Cooper JS, Zhang Q, Pajak TF, Forastiere AA, Jacobs J, Saxman SB, Kish JA, Kim HE, Cmelak AJ, Rotman M, Lustig R, Ensley JF, Thorstad W, Schultz CJ, Yom SS, Ang KK. Long-term follow-up of the RTOG 9501/intergroup phase III trial: postoperative concurrent radiation therapy and chemotherapy in high-risk squamous cell carcinoma of the head and neck. Int J Radiat Oncol Biol Phys. 2012 Dec 1;84(5):1198-205. Epub 2012 Jun 30. [http://www.redjournal.org/article/S0360-3016%2812%2900650-5/abstract link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22749632 PubMed]
-# Bernier J, Domenge C, Ozsahin M, Matuszewska K, Lefèbvre JL, Greiner RH, Giralt J, Maingon P, Rolland F, Bolla M, Cognetti F, Bourhis J, Kirkpatrick A, van Glabbeke M; European Organization for Research and Treatment of Cancer Trial 22931. Postoperative irradiation with or without concomitant chemotherapy for locally advanced head and neck cancer. N Engl J Med. 2004 May 6;350(19):1945-52. [http://www.nejm.org/doi/full/10.1056/NEJMoa032641 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/15128894 PubMed]
+# Bernier J, Domenge C, Ozsahin M, Matuszewska K, Lefèbvre JL, Greiner RH, Giralt J, Maingon P, Rolland F, Bolla M, Cognetti F, Bourhis J, Kirkpatrick A, van Glabbeke M; European Organization for Research and Treatment of Cancer Trial 22931. Postoperative irradiation with or without concomitant chemotherapy for locally advanced head and neck cancer. N Engl J Med. 2004 May 6;350(19):1945-52. [http://www.nejm.org/doi/full/10.1056/NEJMoa032641 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/15128894 PubMed]
-# '''Posthoc analysis:''' Bernier J, Cooper JS, Pajak TF, van Glabbeke M, Bourhis J, Forastiere A, Ozsahin EM, Jacobs JR, Jassem J, Ang KK, Lefèbvre JL. Defining risk levels in locally advanced head and neck cancers: a comparative analysis of concurrent postoperative radiation plus chemotherapy trials of the EORTC (#22931) and RTOG (# 9501). Head Neck. 2005 Oct;27(10):843-50. [http://onlinelibrary.wiley.com/doi/10.1002/hed.20279/full link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/16161069 PubMed]
+# '''Posthoc analysis:''' Bernier J, Cooper JS, Pajak TF, van Glabbeke M, Bourhis J, Forastiere A, Ozsahin EM, Jacobs JR, Jassem J, Ang KK, Lefèbvre JL. Defining risk levels in locally advanced head and neck cancers: a comparative analysis of concurrent postoperative radiation plus chemotherapy trials of the EORTC (#22931) and RTOG (# 9501). Head Neck. 2005 Oct;27(10):843-50. [http://onlinelibrary.wiley.com/doi/10.1002/hed.20279/full link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/16161069 PubMed]
 =Locally advanced disease, chemotherapy & radiation therapy=
@@ Line 139: / Line 149: @@
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
 |[http://www.ejcancer.com/article/S0959-8049%2807%2900262-6/abstract Chitapanarux et al. 2007]
 |style="background-color:#00CD00"|Phase III
-|[[Head_and_neck_cancer#Cisplatin_.26_RT_-.3E_Cisplatin_.26_Fluorouracil|Cisplatin & RT -> Cisplatin & 5-FU]]
+|[[#Cisplatin_.26_RT_-.3E_CF|Cisplatin & RT -> CF]]
+|style="background-color:#eeee00"|Seems not superior
 |-
 |}
@@ Line 162: / Line 174: @@
 ===References===
-# Chitapanarux I, Lorvidhaya V, Kamnerdsupaphon P, Sumitsawan Y, Tharavichitkul E, Sukthomya V, Ford J. Chemoradiotherapy comparing cisplatin versus carboplatin in locally advanced nasopharyngeal cancer: randomised, non-inferiority, open trial. Eur J Cancer. 2007 Jun;43(9):1399-406. Epub 2007 Apr 27. [http://www.ejcancer.com/article/S0959-8049%2807%2900262-6/abstract link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/17467265 PubMed]
+# Chitapanarux I, Lorvidhaya V, Kamnerdsupaphon P, Sumitsawan Y, Tharavichitkul E, Sukthomya V, Ford J. Chemoradiotherapy comparing cisplatin versus carboplatin in locally advanced nasopharyngeal cancer: randomised, non-inferiority, open trial. Eur J Cancer. 2007 Jun;43(9):1399-406. Epub 2007 Apr 27. [http://www.ejcancer.com/article/S0959-8049%2807%2900262-6/abstract link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/17467265 PubMed]
-==Carboplatin, Fluorouracil, concurrent RT {{#subobject:c1e2f9|Regimen=1}}==
+==Carboplatin, Fluorouracil, RT {{#subobject:c1e2f9|Regimen=1}}==
 {| class="wikitable" style="float:right; margin-left: 5px;"
 |-
 |[[#top|back to top]]
 |}
+<br>RT: '''<u>R</u>'''adiation '''<u>T</u>'''herapy
 ===Regimen {{#subobject:98c50f|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
@@ Line 175: / Line 187: @@
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
-|[http://jco.ascopubs.org/content/22/1/69.long Denis et al. 2004 (94-01)]
+|[http://jco.ascopubs.org/content/22/1/69.long Denis et al. 2004 (GORTEC 94-01)]
 |style="background-color:#00CD00"|Phase III
 |[[#Radiation_therapy_9|Radiation therapy]]
+|style="background-color:#00CD00"|Seems to have superior OS
+|-
+|rowspan=2|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(11)70346-1/abstract Bourhis et al. 2012 (GORTEC 99-02)]
+|rowspan=2 style="background-color:#00CD00"|Phase III
+|Carboplatin, Fluorouracil, accelerated concurrent RT
+|style="background-color:#eeee00"|Seems not superior
 |-
-|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(11)70346-1/abstract Bourhis et al. 2012 (GORTEC 99-02)]
+|[[#Radiation_therapy_9|Very accelerated radiation therapy]]
-|style="background-color:#00CD00"|Phase III
+|style="background-color:#00CD00"|Seems to have superior PFS
-|Carboplatin, Fluorouracil, accelerated concurrent RT<br> [[#Radiation_therapy_9|Very accelerated radiation therapy]]
 |-
 |}
@@ Line 193: / Line 211: @@
 ===References===
-# Denis F, Garaud P, Bardet E, Alfonsi M, Sire C, Germain T, Bergerot P, Rhein B, Tortochaux J, Calais G. Final results of the 94-01 French Head and Neck Oncology and Radiotherapy Group randomized trial comparing radiotherapy alone with concomitant radiochemotherapy in advanced-stage oropharynx carcinoma. J Clin Oncol. 2004 Jan 1;22(1):69-76. Epub 2003 Dec 2. [http://jco.ascopubs.org/content/22/1/69.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/14657228 PubMed]
+# Denis F, Garaud P, Bardet E, Alfonsi M, Sire C, Germain T, Bergerot P, Rhein B, Tortochaux J, Calais G. Final results of the 94-01 French Head and Neck Oncology and Radiotherapy Group randomized trial comparing radiotherapy alone with concomitant radiochemotherapy in advanced-stage oropharynx carcinoma. J Clin Oncol. 2004 Jan 1;22(1):69-76. Epub 2003 Dec 2. [http://jco.ascopubs.org/content/22/1/69.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/14657228 PubMed]
-# Bourhis J, Sire C, Graff P, Grégoire V, Maingon P, Calais G, Gery B, Martin L, Alfonsi M, Desprez P, Pignon T, Bardet E, Rives M, Geoffrois L, Daly-Schveitzer N, Sen S, Tuchais C, Dupuis O, Guerif S, Lapeyre M, Favrel V, Hamoir M, Lusinchi A, Temam S, Pinna A, Tao YG, Blanchard P, Aupérin A. Concomitant chemoradiotherapy versus acceleration of radiotherapy with or without concomitant chemotherapy in locally advanced head and neck carcinoma (GORTEC 99-02): an open-label phase 3 randomised trial. Lancet Oncol. 2012 Feb;13(2):145-53. Epub 2012 Jan 18. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(11)70346-1/abstract link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22261362 PubMed]
+# Bourhis J, Sire C, Graff P, Grégoire V, Maingon P, Calais G, Gery B, Martin L, Alfonsi M, Desprez P, Pignon T, Bardet E, Rives M, Geoffrois L, Daly-Schveitzer N, Sen S, Tuchais C, Dupuis O, Guerif S, Lapeyre M, Favrel V, Hamoir M, Lusinchi A, Temam S, Pinna A, Tao YG, Blanchard P, Aupérin A. Concomitant chemoradiotherapy versus acceleration of radiotherapy with or without concomitant chemotherapy in locally advanced head and neck carcinoma (GORTEC 99-02): an open-label phase 3 randomised trial. Lancet Oncol. 2012 Feb;13(2):145-53. Epub 2012 Jan 18. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(11)70346-1/abstract link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22261362 PubMed]
-==Carboplatin, Paclitaxel, concurrent RT {{#subobject:9cccfc|Regimen=1}}==
+==Carboplatin, Paclitaxel, RT {{#subobject:9cccfc|Regimen=1}}==
 {| class="wikitable" style="float:right; margin-left: 5px;"
 |-
 |[[#top|back to top]]
 |}
+<br>RT: '''<u>R</u>'''adiation '''<u>T</u>'''herapy
 ===Regimen #1, accelerated hyperfractionated RT {{#subobject:1fecad|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
@@ Line 223: / Line 241: @@
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |-
-|[http://www.ncbi.nlm.nih.gov/pubmed/9045343 Conley et al. 1997]
+|[https://www.ncbi.nlm.nih.gov/pubmed/9045343 Conley et al. 1997]
-|<span
+|style="background-color:#ff0000"|Pilot, <20 patients
-style="background:#ff0000;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Pilot, <20 patients</span>
 |-
 |[http://www.redjournal.org/article/S0360-3016%2800%2900408-9/abstract Suntharalingam et al. 2000]
@@ Line 250: / Line 263: @@
 ===References===
-# Conley B, Jacobs M, Suntharalingam M, Zacharski D, Ord RA, Gray W, Aisner J. A pilot trial of paclitaxel, carboplatin, and concurrent radiotherapy for unresectable squamous cell carcinoma of the head and neck. Semin Oncol. 1997 Feb;24(1 Suppl 2):S2-78-S2-80. '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/9045343 PubMed]
+# Conley B, Jacobs M, Suntharalingam M, Zacharski D, Ord RA, Gray W, Aisner J. A pilot trial of paclitaxel, carboplatin, and concurrent radiotherapy for unresectable squamous cell carcinoma of the head and neck. Semin Oncol. 1997 Feb;24(1 Suppl 2):S2-78-S2-80. '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/9045343 PubMed]
-# Suntharalingam M, Haas ML, Conley BA, Egorin MJ, Levy S, Sivasailam S, Herman JM, Jacobs MC, Gray WC, Ord RA, Aisner JA, Van Echo DA. The use of carboplatin and paclitaxel with daily radiotherapy in patients with locally advanced squamous cell carcinomas of the head and neck. Int J Radiat Oncol Biol Phys. 2000 Apr 1;47(1):49-56. [http://www.redjournal.org/article/S0360-3016%2800%2900408-9/abstract link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/10758304 PubMed]
+# Suntharalingam M, Haas ML, Conley BA, Egorin MJ, Levy S, Sivasailam S, Herman JM, Jacobs MC, Gray WC, Ord RA, Aisner JA, Van Echo DA. The use of carboplatin and paclitaxel with daily radiotherapy in patients with locally advanced squamous cell carcinomas of the head and neck. Int J Radiat Oncol Biol Phys. 2000 Apr 1;47(1):49-56. [http://www.redjournal.org/article/S0360-3016%2800%2900408-9/abstract link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/10758304 PubMed]
-# Carter DL, Asmar L, Barrera D, Caracandas J, Dakhil JS, McCracken D, O'Rourke MA, Rosenberg RK, Boehm KA, Ilegbodu D, Reid RL. Favorable survival observed after carboplatin, paclitaxel, and concurrent accelerated hyperfractionated radiotherapy for treatment of locally advanced head and neck carcinoma. Invest New Drugs. 2008 Oct;26(5):473-81. Epub 2008 May 13. [http://link.springer.com/article/10.1007%2Fs10637-008-9128-1 link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/18473121 PubMed]
+# Carter DL, Asmar L, Barrera D, Caracandas J, Dakhil JS, McCracken D, O'Rourke MA, Rosenberg RK, Boehm KA, Ilegbodu D, Reid RL. Favorable survival observed after carboplatin, paclitaxel, and concurrent accelerated hyperfractionated radiotherapy for treatment of locally advanced head and neck carcinoma. Invest New Drugs. 2008 Oct;26(5):473-81. Epub 2008 May 13. [http://link.springer.com/article/10.1007%2Fs10637-008-9128-1 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18473121 PubMed]
-==Cetuximab & concurrent RT {{#subobject:5eb410|Regimen=1}}==
+==Cetuximab & RT {{#subobject:5eb410|Regimen=1}}==
 {| class="wikitable" style="float:right; margin-left: 5px;"
 |-
 |[[#top|back to top]]
 |}
+<br>RT: '''<u>R</u>'''adiation '''<u>T</u>'''herapy
 ===Regimen {{#subobject:6e9a4f|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
@@ Line 265: / Line 278: @@
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
 |[http://www.nejm.org/doi/full/10.1056/NEJMoa053422 Bonner et al. 2006 (IMCL-9815)]
 |style="background-color:#00cd00"|Phase III
 |[[#Radiation_therapy_2|Radiation therapy]]
+|style="background-color:#00cd00"|Seems to have superior OS
 |-
 |}
@@ Line 283: / Line 298: @@
 ====Supportive medications====
-*[[Diphenhydramine (Benadryl)]] 50 mg (route not specified) "or an equivalent histamine H1–receptor antagonist" prior to cetuximab
+*[[Diphenhydramine (Benadryl)]] 50 mg (route not specified) "or an equivalent histamine H1–receptor antagonist" prior to [[Cetuximab (Erbitux)]]
 ===References===
-# Bonner JA, Harari PM, Giralt J, Azarnia N, Shin DM, Cohen RB, Jones CU, Sur R, Raben D, Jassem J, Ove R, Kies MS, Baselga J, Youssoufian H, Amellal N, Rowinsky EK, Ang KK. Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med. 2006 Feb 9;354(6):567-78. [http://www.nejm.org/doi/full/10.1056/NEJMoa053422 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/16467544 PubMed]
+# Bonner JA, Harari PM, Giralt J, Azarnia N, Shin DM, Cohen RB, Jones CU, Sur R, Raben D, Jassem J, Ove R, Kies MS, Baselga J, Youssoufian H, Amellal N, Rowinsky EK, Ang KK. Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med. 2006 Feb 9;354(6):567-78. [http://www.nejm.org/doi/full/10.1056/NEJMoa053422 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/16467544 PubMed]
-## '''QoL Analysis:''' Curran D, Giralt J, Harari PM, Ang KK, Cohen RB, Kies MS, Jassem J, Baselga J, Rowinsky EK, Amellal N, Comte S, Bonner JA. Quality of life in head and neck cancer patients after treatment with high-dose radiotherapy alone or in combination with cetuximab. J Clin Oncol. 2007 Jun 1;25(16):2191-7. [http://jco.ascopubs.org/content/25/16/2191.long link to original article] '''contains partial protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/17538164 PubMed]
+## '''QoL Analysis:''' Curran D, Giralt J, Harari PM, Ang KK, Cohen RB, Kies MS, Jassem J, Baselga J, Rowinsky EK, Amellal N, Comte S, Bonner JA. Quality of life in head and neck cancer patients after treatment with high-dose radiotherapy alone or in combination with cetuximab. J Clin Oncol. 2007 Jun 1;25(16):2191-7. [http://jco.ascopubs.org/content/25/16/2191.long link to original article] '''contains partial protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/17538164 PubMed]
-## '''Update:''' Bonner JA, Harari PM, Giralt J, Cohen RB, Jones CU, Sur RK, Raben D, Baselga J, Spencer SA, Zhu J, Youssoufian H, Rowinsky EK, Ang KK. Radiotherapy plus cetuximab for locoregionally advanced head and neck cancer: 5-year survival data from a phase 3 randomised trial, and relation between cetuximab-induced rash and survival. Lancet Oncol. 2010 Jan;11(1):21-8. Epub 2009 Nov 10. [http://www.sciencedirect.com/science/article/pii/S1470204509703110 link to original article] '''contains partial protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/19897418 PubMed]
+## '''Update:''' Bonner JA, Harari PM, Giralt J, Cohen RB, Jones CU, Sur RK, Raben D, Baselga J, Spencer SA, Zhu J, Youssoufian H, Rowinsky EK, Ang KK. Radiotherapy plus cetuximab for locoregionally advanced head and neck cancer: 5-year survival data from a phase 3 randomised trial, and relation between cetuximab-induced rash and survival. Lancet Oncol. 2010 Jan;11(1):21-8. Epub 2009 Nov 10. [http://www.sciencedirect.com/science/article/pii/S1470204509703110 link to original article] '''contains partial protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19897418 PubMed]
 ## '''Retrospective subgroup analysis:''' Rosenthal DI, Harari PM, Giralt J, Bell D, Raben D, Liu J, Schulten J, Ang KK, Bonner JA. Association of Human Papillomavirus and p16 Status With Outcomes in the IMCL-9815 Phase III Registration Trial for Patients With Locoregionally Advanced Oropharyngeal Squamous Cell Carcinoma of the Head and Neck Treated With Radiotherapy With or Without Cetuximab. J Clin Oncol. 2016 Apr 20;34(12):1300-8. Epub 2015 Dec 28. [http://jco.ascopubs.org/content/34/12/1300.full link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/26712222 PubMed]
-==Cisplatin & concurrent RT {{#subobject:c7061f|Regimen=1}}==
+==CF -> Carboplatin & RT {{#subobject:b5390f|Regimen=1}}==
 {| class="wikitable" style="float:right; margin-left: 5px;"
 |-
 |[[#top|back to top]]
 |}
+CF -> Carboplatin & RT: '''<u>C</u>'''isplatin and '''<u>F</u>'''luorouracil followed by Carboplatin and '''<u>R</u>'''adiation '''<u>T</u>'''herapy
-===Regimen #1 {{#subobject:aca3c0|Variant=1}}===
+===Regimen {{#subobject:37c90b|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
@@ Line 304: / Line 320: @@
 |[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
-|[http://jco.ascopubs.org/content/21/1/92.long Adelstein et al. 2003]
+|[http://www.nejm.org/doi/full/10.1056/NEJMoa070956 Posner et al. 2007 (TAX 324)]
 |style="background-color:#00CD00"|Phase III
-|[[#Cisplatin.2C_Fluorouracil_.28PF.29.2C_concurrent_RT|Cisplatin, 5-FU, RT]]<br> [[#Radiation_therapy_9|Radiation therapy]]
+|[[#TPF_-.3E_Carboplatin_.26_RT|TPF -> Carboplatin & RT]]
-|
+|style="background-color:#ff0000"|Inferior OS
-|-
-|[http://www.nejm.org/doi/full/10.1056/NEJMoa031317 Forastiere et al. 2003 (RTOG 91-11)]
-|style="background-color:#00CD00"|Phase III
-|[[#Cisplatin_.26_Fluorouracil_.28PF.29_-.3E_sequential_RT|Cisplatin & 5-FU -> RT]]<br> [[#Radiation_therapy_9|Radiation therapy]]
-|
-|-
-|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(16)30410-7/fulltext Sun et al. 2016]
-|style="background-color:#00CD00"|Phase III
-|[[#Cisplatin.2C_Fluorouracil.2C_Docetaxel_.28DCF.2C_TPF.29_-.3E_Cisplatin_.26_concurrent_RT|TPF -> Cisplatin & RT]]
-|style="background-color:#ff0000"|Seems to have inferior FFS
 |-
 |}
+====Chemotherapy====
+*[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV over 30 to 180 minutes once on day 1, '''given first'''
+*[[Fluorouracil (5-FU)]] 1000 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours on days 1 to 4 (total dose per cycle: 4000 mg/m<sup>2</sup>)
+'''21-day cycle for 3 cycles; then start chemoradiotherapy 3 to 8 weeks after the start of cycle 3:'''
 ====Chemoradiotherapy====
-*[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV once per day on days 1, 22, 43
+*[[Carboplatin (Paraplatin)]] AUC 1.5 IV over 1 hour once per day on days 1, 8, 15, 22, 29, 36, 43
-*Concurrent radiation therapy as follows:
+*Concurrent radiation therapy, 2 Gy fractions x 35 to 37 fractions (total dose: 70 to 74 Gy), given 5 times per week over 7 to 7.5 weeks
-**'''Adelstein et al. 2003''' and '''RTOG 91-11''': 2 Gy fractions x 35 fractions (total dose: 70 Gy), given 5 times per week over 7 weeks
-**'''Sun et al. 2016''': see paper for details
+'''7 to 7.5-week course;''' surgery "performed 6 to 12 weeks after completion of chemoradiotherapy for patients who had an initial nodal stage of N2 and a partial response to induction chemotherapy, N3 disease, or residual disease after chemoradiotherapy."
-'''One course'''
+===References===
+# Posner MR, Hershock DM, Blajman CR, Mickiewicz E, Winquist E, Gorbounova V, Tjulandin S, Shin DM, Cullen K, Ervin TJ, Murphy BA, Raez LE, Cohen RB, Spaulding M, Tishler RB, Roth B, Viroglio Rdel C, Venkatesan V, Romanov I, Agarwala S, Harter KW, Dugan M, Cmelak A, Markoe AM, Read PW, Steinbrenner L, Colevas AD, Norris CM Jr, Haddad RI; TAX 324 Study Group. Cisplatin and fluorouracil alone or with docetaxel in head and neck cancer. N Engl J Med. 2007 Oct 25;357(17):1705-15. [http://www.nejm.org/doi/full/10.1056/NEJMoa070956 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/17960013 PubMed]
-===Regimen #2 {{#subobject:b44282|Variant=1}}===
+==CF -> Cisplatin & RT {{#subobject:c0e730|Regimen=1}}==
+{| class="wikitable" style="float:right; margin-left: 5px;"
+|-
+|[[#top|back to top]]
+|}
+CF -> Cisplatin & RT: '''<u>C</u>'''isplatin and '''<u>F</u>'''luorouracil followed by Cisplatin and '''<u>R</u>'''adiation '''<u>T</u>'''herapy
+===Regimen {{#subobject:fdece8|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
-|[http://jco.ascopubs.org/content/32/27/2940.long Ang et al. 2014 (RTOG 0522)]
+|[http://jco.ascopubs.org/content/23/34/8636.long Hitt et al. 2005]
 |style="background-color:#00CD00"|Phase III
-|Cetuximab, Cisplatin, RT
+|[[#PCF_-.3E_Cisplatin_.26_RT|PCF -> Cisplatin & RT]]
+|style="background-color:#ff0000"|Inferior CR rate
 |-
 |}
+====Chemotherapy====
+*[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV once on day 1
+*[[Fluorouracil (5-FU)]] 1000 mg/m<sup>2</sup>/day IV continuous infusion over 5 days on days 1 to 5 (total dose per cycle: 5000 mg/m<sup>2</sup>)
+'''3-week cycle for 3 cycles'''
+''Patients then undergo ENT evaluation and CT imaging of the primary tumor and neck. Patients with complete response (CR) or partial response of >80% in the primary tumor and no evidence of progression in neck lymph nodes proceeded to chemoradiotherapy. "Patients with a PR of less than 80% or stable disease in the neck lymph nodes (especially if N2 or N3 disease) after induction CT were referred to surgery for neck dissection, if the surgeons were in agreement, before the administration of CRT." Patients with no response or progression of disease were taken off study.''
 ====Chemoradiotherapy====
-*[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV once per day on days 1 & 22
+*[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV once per day on days 1, 22, 43
-*Concurrent radiation therapy by one of the following:
+*Concurrent radiation therapy to primary tumor, 2 Gy fractions x 35 fractions (total dose: 70 Gy), given 5 times per week over 7 weeks. Nodal areas not involved by tumor received 50 Gy.
-**IMRT: 2 Gy fractions x 35 fractions (total dose: 70 Gy), given 6 times per week over 6 weeks
-**Accelerated radiotherapy: 42 fractions (total dose: 72 Gy), given twice per day for 12 days then once per day over 6 weeks
-'''One course'''
+===References===
+# Hitt R, López-Pousa A, Martínez-Trufero J, Escrig V, Carles J, Rizo A, Isla D, Vega ME, Martí JL, Lobo F, Pastor P, Valentí V, Belón J, Sánchez MA, Chaib C, Pallarés C, Antón A, Cervantes A, Paz-Ares L, Cortés-Funes H. 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 Dec 1;23(34):8636-45. Epub 2005 Nov 7. [http://jco.ascopubs.org/content/23/34/8636.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/16275937 PubMed]
-===Regimen #3 {{#subobject:b41045|Variant=1}}===
+==CF & RT {{#subobject:4c4db1|Regimen=1}}==
+{| class="wikitable" style="float:right; margin-left: 5px;"
+|-
+|[[#top|back to top]]
+|}
+CF & RT: '''<u>C</u>'''isplatin and '''<u>F</u>'''luorouracil with concurrent '''<u>R</u>'''adiation '''<u>T</u>'''herapy
+===Regimen #1 {{#subobject:8b995f|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
-|[http://jnci.oxfordjournals.org/content/97/7/536.long Chan et al. 2005]
+|[http://jco.ascopubs.org/content/12/2/385.long Taylor et al. 1994]
 |style="background-color:#00CD00"|Phase III
-|[[#Radiation_therapy_9|Radiation therapy]]
+|[[#CF_-.3E_RT|CF -> RT]]
+|style="background-color:#00CD00"|Superior ORR
 |-
 |}
+====Chemotherapy====
+*[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV over 15 minutes once on day 1
+*[[Fluorouracil (5-FU)]] 800 mg/m<sup>2</sup>/day IV continuous infusion over 120 hours on days 1 to 5 (total dose per cycle: 4000 mg/m<sup>2</sup>)
-''This study only involved patients with locoregionally advanced nasopharyngeal carcinoma.''
+'''2-week cycle for 7 cycles given together with the following concurrent radiation therapy:'''
-====Chemoradiotherapy====
-*[[Cisplatin (Platinol)]] 40 mg/m<sup>2</sup> in 1 liter normal saline IV over 2 hours once per day on days 1, 8, 15, 22, 29, 36, 43
-*Concurrent radiation therapy, 2 Gy fractions x 33 fractions (total dose: 66 Gy), given 5 times per week over 6.5 weeks. See Chan et al. 2005 for additional information about boost doses.
-'''One course'''
+====Radiotherapy====
+*Concurrent radiation therapy, 2 Gy fractions x 35 fractions (total dose: 70 Gy), given 5 times per week on weeks 1, 3, 5, 7, 9, 11, 13
-===References===
+===Regimen #2 {{#subobject:f7b52|Variant=1}}===
-# Adelstein DJ, Li Y, Adams GL, Wagner H Jr, Kish JA, Ensley JF, Schuller DE, Forastiere AA. 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 Jan 1;21(1):92-8. [http://jco.ascopubs.org/content/21/1/92.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/12506176 PubMed]
-# Forastiere AA, Goepfert H, Maor M, Pajak TF, Weber R, Morrison W, Glisson B, Trotti A, Ridge JA, Chao C, Peters G, Lee DJ, Leaf A, Ensley J, Cooper J. Concurrent chemotherapy and radiotherapy for organ preservation in advanced laryngeal cancer. N Engl J Med. 2003 Nov 27;349(22):2091-8. [http://www.nejm.org/doi/full/10.1056/NEJMoa031317 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/14645636 PubMed]
-## '''Update:''' Forastiere AA, Zhang Q, Weber RS, Maor MH, Goepfert H, Pajak TF, Morrison W, Glisson B, Trotti A, Ridge JA, Thorstad W, Wagner H, Ensley JF, Cooper JS. Long-term results of RTOG 91-11: a comparison of three nonsurgical treatment strategies to preserve the larynx in patients with locally advanced larynx cancer. J Clin Oncol. 2013 Mar 1;31(7):845-52. Epub 2012 Nov 26. [http://jco.ascopubs.org/content/31/7/845.long link to original article] '''contains partial protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/23182993 PubMed]
-# Chan AT, Leung SF, Ngan RK, Teo PM, Lau WH, Kwan WH, Hui EP, Yiu HY, Yeo W, Cheung FY, Yu KH, Chiu KW, Chan DT, Mok TS, Yau S, Yuen KT, Mo FK, Lai MM, Ma BB, Kam MK, Leung TW, Johnson PJ, Choi PH, Zee BC. Overall survival after concurrent cisplatin-radiotherapy compared with radiotherapy alone in locoregionally advanced nasopharyngeal carcinoma. J Natl Cancer Inst. 2005 Apr 6;97(7):536-9. [http://jnci.oxfordjournals.org/content/97/7/536.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/15812080 PubMed]
-# Ang KK, Zhang Q, Rosenthal DI, Nguyen-Tan PF, Sherman EJ, Weber RS, Galvin JM, Bonner JA, Harris J, El-Naggar AK, Gillison ML, Jordan RC, Konski AA, Thorstad WL, Trotti A, Beitler JJ, Garden AS, Spanos WJ, Yom SS, Axelrod RS. Randomized phase III trial of concurrent accelerated radiation plus cisplatin with or without cetuximab for stage III to IV head and neck carcinoma: RTOG 0522. J Clin Oncol. 2014 Sep 20;32(27):2940-50. [http://jco.ascopubs.org/content/32/27/2940.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/25154822 PubMed]
-# Sun Y, Li WF, Chen NY, Zhang N, Hu GQ, Xie FY, Sun Y, Chen XZ, Li JG, Zhu XD, Hu CS, Xu XY, Chen YY, Hu WH, Guo L, Mo HY, Chen L, Mao YP, Sun R, Ai P, Liang SB, Long GX, Zheng BM, Feng XL, Gong XC, Li L, Shen CY, Xu JY, Guo Y, Chen YM, Zhang F, Lin L, Tang LL, Liu MZ, Ma J. Induction chemotherapy plus concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: a phase 3, multicentre, randomised controlled  trial. Lancet Oncol. 2016 Sep 26. [Epub ahead of print] [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(16)30410-7/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/27686945 PubMed]
-==Cisplatin & RT -> Cisplatin & Fluorouracil {{#subobject:94720|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
-RT: '''<u>R</u>'''adiation '''<u>T</u>'''herapy
-===Regimen #1 {{#subobject:e1c43a|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
-|[http://jco.ascopubs.org/content/16/4/1310.long Al-Sarraf et al. 1998 (Intergroup 0099)]
+|rowspan=2|[http://jco.ascopubs.org/content/22/14/2856.long Garden et al. 2004 (RTOG 97-03)]
-|style="background-color:#00CD00"|Phase III
+|rowspan=2 style="background-color:#00CD00"|Randomized Phase II
-|[[Head_and_neck_cancer#Radiation_therapy_9|Radiation therapy]]
+|[[#Cisplatin.2C_Paclitaxel.2C_RT|Cisplatin, Paclitaxel, RT]]
+|style="background-color:#eeee00"|Seems not superior
+|-
+|[[#Fluorouracil.2C_Hydroxyurea.2C_RT|5-FU, Hydroxyurea, RT]]
+|style="background-color:#eeee00"|Seems not superior
 |-
 |}
-''This study only involved patients with stage III and IV nasopharynx cancers without evidence of metastases.''
+''Note: Garden et al. 2004 described this regimen in an unclear way, and it is not clear exactly how many doses or when each chemotherapy is given. Specifically, it's confusing how people would "receive their treatments every week for 7 consecutive weeks," yet fluorouracil (and maybe also cisplatin) would be given "daily for the final 10 days of radiation treatment."''
 ====Chemoradiotherapy====
-*[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV over 15 to 20 minutes once per day on days 1, 22, 43
+*[[Cisplatin (Platinol)]] 10 mg/m<sup>2</sup> IV once per day (unable to discern what days this is given on based on the paper)
-*Concurrent radiation therapy to the primary tumor, 1.8 to 2 Gy fractions x 35 to 39 fractions (total dose: 70 Gy), given 5 times per week. Minimum total dose to neck nodes is 50 Gy for N0 disease; 66 Gy for nodes =2 cm in size; 70 Gy for nodes >2 cm.
+*[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup>/day IV continuous infusion over 10 days on the last 10 days of radiation treatments
+*Concurrent radiation therapy, 2 Gy fractions x 35 fractions (total dose: 70 Gy), given 5 times per week over 7 weeks
-====Supportive medications====
+'''7-week course of therapy'''
-*Forced hydration: 5% dextrose in 1/2 normal saline with 40 mEq KCl, 2000 mL IV continuous infusion over 24 hours given twice, before each dose of cisplatin and after the second mannitol infusion
-*Mannitol 12.5 g IV bolus prior to cisplatin
-*5% dextrose in 1/2 normal saline with 30 mEq KCl and mannitol 25 g, 1000 mL IV over 4 hours immediately after cisplatin
-*[[Antiemesis|Antiemetic]] such as [[Prochlorperazine (Compazine)]] 25 mg rectal suppository given 30 minutes prior to cisplatin; [[Prochlorperazine (Compazine)]] 10 mg IM every 4 hours as needed for nausea after cisplatin
-'''7 to 8-week course, followed 4 weeks after the last dose of cisplatin used in Chemoradiotherapy by:'''
+===References===
+# Taylor SG 4th, Murthy AK, Vannetzel JM, Colin P, Dray M, Caldarelli DD, Shott S, Vokes E, Showel JL, Hutchinson JC et al. Randomized comparison of neoadjuvant cisplatin and fluorouracil infusion followed by radiation versus concomitant treatment in advanced head and neck cancer. J Clin Oncol. 1994 Feb;12(2):385-95. [http://jco.ascopubs.org/content/12/2/385.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/8113846 PubMed]
+# Adelstein DJ, Li Y, Adams GL, Wagner H Jr, Kish JA, Ensley JF, Schuller DE, Forastiere AA. 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 Jan 1;21(1):92-8. [http://jco.ascopubs.org/content/21/1/92.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/12506176 PubMed]
+# Garden AS, Harris J, Vokes EE, Forastiere AA, Ridge JA, Jones C, Horwitz EM, Glisson BS, Nabell L, Cooper JS, Demas W, Gore E. Preliminary results of Radiation Therapy Oncology Group 97-03: a randomized phase ii trial of concurrent radiation and chemotherapy for advanced squamous cell carcinomas of the head and neck. J Clin Oncol. 2004 Jul 15;22(14):2856-64. [http://jco.ascopubs.org/content/22/14/2856.long link to original article] '''contains verified protocol'''--see comment above [https://www.ncbi.nlm.nih.gov/pubmed/15254053 PubMed]
-====Chemotherapy====
+==CF -> RT {{#subobject:8471da|Regimen=1}}==
-*[[Cisplatin (Platinol)]] 80 mg/m<sup>2</sup> IV over 15 to 20 minutes once on day 1
+{| class="wikitable" style="float:right; margin-left: 5px;"
-*[[Fluorouracil (5-FU)]] 1000 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours on days 1 to 4 (total dose per cycle: 4000 mg/m<sup>2</sup>)
+|-
+|[[#top|back to top]]
+|}
+CF -> RT: '''<u>C</u>'''isplatin and '''<u>F</u>'''luorouracil followed by '''<u>R</u>'''adiation '''<u>T</u>'''herapy
-====Supportive medications====
+===Regimen #1 {{#subobject:62ca18|Variant=1}}===
-*Al-Sarraf et al. 1998 did not specifically say whether the same hydration and antiemetics were used for this chemotherapy as in Chemoradiotherapy.
-'''28-day cycle for 3 cycles'''
-===Regimen #2 {{#subobject:2437a0|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
-|[http://www.ejcancer.com/article/S0959-8049%2807%2900262-6/abstract Chitapanarux et al. 2007]
+|rowspan=2|[http://www.nejm.org/doi/full/10.1056/NEJMoa031317 Forastiere et al. 2003 (RTOG 91-11)]
-|style="background-color:#00CD00"|Phase III
+|rowspan=2 style="background-color:#00CD00"|Phase III
-|[[Head_and_neck_cancer#Carboplatin_.26_RT_-.3E_Carboplatin_.26_Fluorouracil|Carboplatin & RT -> Carboplatin & 5-FU]]
+|[[#Cisplatin_.26_RT_2|Cisplatin & RT]]
+|style="background-color:#d3d3d3"|Not reported
+|-
+|[[#Radiation_therapy_9|Radiation therapy]]
+|style="background-color:#00CD00"|Seems to have superior DFS
 |-
 |}
+====Chemotherapy====
+*[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV once on day 1
+*[[Fluorouracil (5-FU)]] 1000 mg/m<sup>2</sup>/day IV continuous infusion over 120 hours on days 1 to 5 (total dose per cycle: 5000 mg/m<sup>2</sup>)
-''This study only involved patients with locoregionally advanced nasopharyngeal carcinoma.''
+'''21-day cycle for 2 cycles'''
-====Chemoradiotherapy====
+''After cycle 2, patients are evaluated by indirect laryngoscopy and CT neck. Patients with complete or partial response receive a '''third cycle of induction chemotherapy as described above''', followed by radiation therapy. Patients with worse than a partial response underwent laryngectomy and adjuvant radiation therapy.''
-*[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV over 3 hours once per day on days 1, 22, 43
-*Concurrent radiation therapy to the primary tumor, 2 Gy fractions x 35 fractions (total dose: 70 Gy), given 5 times per week over 7 weeks
-'''7-week course, followed 4 weeks after the end of radiation therapy by:'''
+====Radiotherapy====
+*Radiation therapy, 2 Gy fractions x 35 fractions (total dose: 70 Gy), given 5 times per week over 7 weeks
-====Chemotherapy====
+===Regimen #2 {{#subobject:593c5f|Variant=1}}===
-*[[Cisplatin (Platinol)]] 80 mg/m<sup>2</sup> IV once on day 1
+{| border="1" style="text-align:center;" !align="left"
-*[[Fluorouracil (5-FU)]] 1000 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours on days 1 to 4 (total dose per cycle: 4000 mg/m<sup>2</sup>)
-'''28-day cycle for 3 cycles'''
-===References===
-# Al-Sarraf M, LeBlanc M, Giri PG, Fu KK, Cooper J, Vuong T, Forastiere AA, Adams G, Sakr WA, Schuller DE, Ensley JF. Chemoradiotherapy versus radiotherapy in patients with advanced nasopharyngeal cancer: phase III randomized Intergroup study 0099. J Clin Oncol. 1998 Apr;16(4):1310-7. [http://jco.ascopubs.org/content/16/4/1310.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/9552031 PubMed]
-# Chitapanarux I, Lorvidhaya V, Kamnerdsupaphon P, Sumitsawan Y, Tharavichitkul E, Sukthomya V, Ford J. Chemoradiotherapy comparing cisplatin versus carboplatin in locally advanced nasopharyngeal cancer: randomised, non-inferiority, open trial. Eur J Cancer. 2007 Jun;43(9):1399-406. Epub 2007 Apr 27. [http://www.ejcancer.com/article/S0959-8049%2807%2900262-6/abstract link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/17467265 PubMed]
-==Cisplatin, Fluorouracil (PF), concurrent RT {{#subobject:4c4db1|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
-PF: '''<u>P</u>'''latinol (Cisplatin), '''<u>F</u>'''luorouracil
-===Regimen #1 {{#subobject:8b995f|Variant=1}}===
-{| border="1" style="text-align:center;" !align="left"
 |'''Study'''
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
 |[http://jco.ascopubs.org/content/12/2/385.long Taylor et al. 1994]
 |style="background-color:#00CD00"|Phase III
-|[[#Cisplatin_.26_Fluorouracil_.28PF.29_-.3E_sequential_RT|Cisplatin & 5-FU -> RT]]
+|[[#CF_.26_RT|CF & RT]]
+|style="background-color:#ff0000"|Inferior ORR
 |-
 |}
 ====Chemotherapy====
-*[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV over 15 minutes once on day 1
+*[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV over 15 minutes once on day 1
-*[[Fluorouracil (5-FU)]] 800 mg/m<sup>2</sup>/day IV continuous infusion over 120 hours on days 1 to 5 (total dose per cycle: 4000 mg/m<sup>2</sup>)
+*[[Fluorouracil (5-FU)]] 1000 mg/m<sup>2</sup>/day IV continuous infusion over 120 hours on days 1 to 5 (total dose per cycle: 5000 mg/m<sup>2</sup>)
-'''2-week cycle for 7 cycles given together with the following concurrent radiation therapy:'''
+'''21-day cycle for 3 cycles, followed by:'''
 ====Radiotherapy====
-*Concurrent radiation therapy, 2 Gy fractions x 35 fractions (total dose: 70 Gy), given 5 times per week
+*Radiation therapy, 1.8 to 2 Gy fractions to a total dose of 70 Gy, given 5 times per week over 7 to 8 weeks
-on weeks 1, 3, 5, 7, 9, 11, 13
+===Regimen #3 {{#subobject:de6fdb|Variant=1}}===
-===Regimen #2 {{#subobject:f7b52|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
-|[http://jco.ascopubs.org/content/22/14/2856.long Garden et al. 2004 (RTOG 97-03)]
+|[http://jnci.oxfordjournals.org/content/101/7/498.long Pointreau et al. 2009 (GORTEC)]
-|style="background-color:#00CD00"|Randomized Phase II
+|style="background-color:#00CD00"|Phase III
-|[[#Cisplatin.2C_Paclitaxel.2C_concurrent_RT|Cisplatin, Paclitaxel, RT]]<br> [[#Fluorouracil.2C_Hydroxyurea.2C_concurrent_RT|5-FU, Hydroxyurea, RT]]
+|[[#TPF_-.3E_RT|TPF -> RT]]
+|style="background-color:#ff0000"|Inferior ORR
 |-
 |}
-''Note: Garden et al. 2004 described this regimen in an unclear way, and it is not clear exactly how many doses or when each chemotherapy is given. Specifically, it's confusing how people would "receive their treatments every week for 7 consecutive weeks," yet fluorouracil (and maybe also cisplatin) would be given "daily for the final 10 days of radiation treatment."''
+====Chemotherapy====
-====Chemoradiotherapy====
+*[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV over 1 hour once on day 1
-*[[Cisplatin (Platinol)]] 10 mg/m<sup>2</sup> IV once per day (unable to discern what days this is given on based on the paper)
+*[[Fluorouracil (5-FU)]] 1000 mg/m<sup>2</sup>/day IV continuous infusion over 5 days on days 1 to 5 (total dose per cycle: 5000 mg/m<sup>2</sup>)
-*[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup>/day IV continuous infusion over 10 days on the last 10 days of radiation treatments
-*Concurrent radiation therapy, 2 Gy fractions x 35 fractions (total dose: 70 Gy), given 5 times per week over 7 weeks
-'''7-week course of therapy'''
+====Supportive medications====
+*Normal saline (use of mannitol, KCl, and magnesium sulfate per institutional protocol) 1000 mL IV given twice, before and after [[Cisplatin (Platinol)]]
-===References===
+'''21-day cycle for 3 cycles'''
-# Taylor SG 4th, Murthy AK, Vannetzel JM, Colin P, Dray M, Caldarelli DD, Shott S, Vokes E, Showel JL, Hutchinson JC et al. Randomized comparison of neoadjuvant cisplatin and fluorouracil infusion followed by radiation versus concomitant treatment in advanced head and neck cancer. J Clin Oncol. 1994 Feb;12(2):385-95. [http://jco.ascopubs.org/content/12/2/385.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/8113846 PubMed]
-# Adelstein DJ, Li Y, Adams GL, Wagner H Jr, Kish JA, Ensley JF, Schuller DE, Forastiere AA. 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 Jan 1;21(1):92-8. [http://jco.ascopubs.org/content/21/1/92.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/12506176 PubMed]
-# Garden AS, Harris J, Vokes EE, Forastiere AA, Ridge JA, Jones C, Horwitz EM, Glisson BS, Nabell L, Cooper JS, Demas W, Gore E. Preliminary results of Radiation Therapy Oncology Group 97-03: a randomized phase ii trial of concurrent radiation and chemotherapy for advanced squamous cell carcinomas of the head and neck. J Clin Oncol. 2004 Jul 15;22(14):2856-64. [http://jco.ascopubs.org/content/22/14/2856.long link to original article] '''contains verified protocol'''--see comment above [http://www.ncbi.nlm.nih.gov/pubmed/15254053 PubMed]
-==Cisplatin & Fluorouracil (PF) -> sequential RT {{#subobject:8471da|Regimen=1}}==
+''Patients who responded to induction chemotherapy proceeded to radiation therapy within 3 to 7 weeks of finishing chemotherapy. Patients who did not respond to induction chemotherapy proceeded to surgery and postoperative radiotherapy (see Pointreau et al. 2009 for details).''
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
-PF: '''<u>P</u>'''latinol (Cisplatin), '''<u>F</u>'''luorouracil
-===Regimen #1 {{#subobject:62ca18|Variant=1}}===
+====Radiotherapy====
+*Radiation therapy to the primary tumor and involved lymph nodes, 2 Gy fractions x 35 fractions (total dose: 70 Gy), given 5 times per week over 7 weeks. Prophylactic radiation to the volume at risk for microscopic disease, 2 Gy fractions x 25 to 27 fractions (total dose: 50 to 54 Gy), given 5 times per week.
+*"Chemotherapy (cisplatin, carboplatin, and 5-fluorouracil or a combination of two drugs) during radiotherapy was allowed for all patients who were treated at the same institute, according to its practice." No further details available.
+===Regimen #4 {{#subobject:23fcf5|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
-|[http://www.nejm.org/doi/full/10.1056/NEJMoa031317 Forastiere et al. 2003 (RTOG 91-11)]
+|[http://www.nejm.org/doi/full/10.1056/NEJMoa071028 Vermorken et al. 2007 (EORTC 24971/TAX 323)]
 |style="background-color:#00CD00"|Phase III
-|[[#Cisplatin_.26_concurrent_RT_2|Cisplatin & RT]]<br> [[#Radiation_therapy_9|Radiation therapy]]
+|[[#TPF_-.3E_RT|TPF -> RT]]
+|style="background-color:#ff0000"|Seems to have inferior OS
 |-
 |}
 ====Chemotherapy====
-*[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV once on day 1
+*[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV over 1 hour once on day 1, '''given first before fluorouracil'''
-*[[Fluorouracil (5-FU)]] 1000 mg/m<sup>2</sup>/day IV continuous infusion over 120 hours on days 1 to 5 (total dose per cycle: 5000 mg/m<sup>2</sup>)
+*[[Fluorouracil (5-FU)]] 1000 mg/m<sup>2</sup>/day IV continuous infusion over 5 days on days 1 to 5 (total dose per cycle: 5000 mg/m<sup>2</sup>)
+====Supportive medications====
+*"Adequate [[Antiemesis|antiemetic]] medications during chemotherapy"
+*Prophylactic [[Filgrastim (Neupogen)|granulocyte colony-stimulating factor]] only allowed for patients who had "febrile neutropenia or infection, a delay in recovery of the absolute neutrophil count at day 28, or grade 4 neutropenia persisting for 7 days or more."
-'''21-day cycle for 2 cycles'''
+'''21-day cycle for 4 cycles'''
-''After cycle 2, patients are evaluated by indirect laryngoscopy and CT neck. Patients with complete or partial response receive a '''third cycle of induction chemotherapy as described above''', followed by radiation therapy. Patients with worse than a partial response underwent laryngectomy and adjuvant radiation therapy.''
+''Patients without progressive disease and who had recovery of marrow function, resolution of mucositis, and healed from any dental procedures started radiation therapy within 4 to 7 weeks of finishing chemotherapy:''
 ====Radiotherapy====
-*Radiation therapy, 2 Gy fractions x 35 fractions (total dose: 70 Gy), given 5 times per week over 7 weeks
+*Radiation therapy over 7 weeks with one of the following (further details not provided):
+**Conventional fractionation, total dose 66 to 70 Gy
+**Accelerated fractionation, total dose 70 Gy
+**Hyperfractionated, total dose 74 Gy
+===References===
+# Taylor SG 4th, Murthy AK, Vannetzel JM, Colin P, Dray M, Caldarelli DD, Shott S, Vokes E, Showel JL, Hutchinson JC et al. Randomized comparison of neoadjuvant cisplatin and fluorouracil infusion followed by radiation versus concomitant treatment in advanced head and neck cancer. J Clin Oncol. 1994 Feb;12(2):385-95. [http://jco.ascopubs.org/content/12/2/385.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/8113846 PubMed]
+# Forastiere AA, Goepfert H, Maor M, Pajak TF, Weber R, Morrison W, Glisson B, Trotti A, Ridge JA, Chao C, Peters G, Lee DJ, Leaf A, Ensley J, Cooper J. Concurrent chemotherapy and radiotherapy for organ preservation in advanced laryngeal cancer. N Engl J Med. 2003 Nov 27;349(22):2091-8. [http://www.nejm.org/doi/full/10.1056/NEJMoa031317 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/14645636 PubMed]
+## '''Update:''' Forastiere AA, Zhang Q, Weber RS, Maor MH, Goepfert H, Pajak TF, Morrison W, Glisson B, Trotti A, Ridge JA, Thorstad W, Wagner H, Ensley JF, Cooper JS. Long-term results of RTOG 91-11: a comparison of three nonsurgical treatment strategies to preserve the larynx in patients with locally advanced larynx cancer. J Clin Oncol. 2013 Mar 1;31(7):845-52. Epub 2012 Nov 26. [http://jco.ascopubs.org/content/31/7/845.long link to original article] '''contains partial protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23182993 PubMed]
+# Vermorken JB, Remenar E, van Herpen C, Gorlia T, Mesia R, Degardin M, Stewart JS, Jelic S, Betka J, Preiss JH, van den Weyngaert D, Awada A, Cupissol D, Kienzer HR, Rey A, Desaunois I, Bernier J, Lefebvre JL; EORTC 24971/TAX 323 Study Group. Cisplatin, fluorouracil, and docetaxel in unresectable head and neck cancer. N Engl J Med. 2007 Oct 25;357(17):1695-704. [http://www.nejm.org/doi/full/10.1056/NEJMoa071028 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/17960012 PubMed]
+## '''QoL Analysis:''' van Herpen CM, Mauer ME, Mesia R, Degardin M, Jelic S, Coens C, Betka J, Bernier J, Remenar E, Stewart JS, Preiss JH, van den Weyngaert D, Bottomley A, Vermorken JB; EORTC Head and Neck Group. Short-term health-related quality of life and symptom control with docetaxel, cisplatin, 5-fluorouracil and cisplatin (TPF), 5-fluorouracil (PF) for induction in unresectable locoregionally advanced head and neck cancer patients (EORTC 24971/TAX 323). Br J Cancer. 2010 Oct 12;103(8):1173-81. Epub 2010 Sep 14. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2967049/ link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/20842129 PubMed]
+# Pointreau Y, Garaud P, Chapet S, Sire C, Tuchais C, Tortochaux J, Faivre S, Guerrif S, Alfonsi M, Calais G. Randomized trial of induction chemotherapy with cisplatin and 5-fluorouracil with or without docetaxel for larynx preservation. J Natl Cancer Inst. 2009 Apr 1;101(7):498-506. Epub 2009 Mar 24. [http://jnci.oxfordjournals.org/content/101/7/498.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19318632 PubMed]
-===Regimen #2 {{#subobject:593c5f|Variant=1}}===
+==Cisplatin & RT {{#subobject:c7061f|Regimen=1}}==
+{| class="wikitable" style="float:right; margin-left: 5px;"
+|-
+|[[#top|back to top]]
+|}
+<br>RT: '''<u>R</u>'''adiation '''<u>T</u>'''herapy
+===Regimen #1 {{#subobject:aca3c0|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
+|-
+|rowspan=2|[http://jco.ascopubs.org/content/21/1/92.long Adelstein et al. 2003]
+|rowspan=2 style="background-color:#00CD00"|Phase III
+|[[#CF_.26_RT|CF & RT]]
+|style="background-color:#eeee00"|Seems not superior
+|-
+|[[#Radiation_therapy_9|Radiation therapy]]
+|style="background-color:#00CD00"|Seems to have superior OS
+|-
+|rowspan=2|[http://www.nejm.org/doi/full/10.1056/NEJMoa031317 Forastiere et al. 2003 (RTOG 91-11)]
+|rowspan=2 style="background-color:#00CD00"|Phase III
+|[[#CF_-.3E_RT|CF -> RT]]
+|style="background-color:#d3d3d3"|Not reported
+|-
+|[[#Radiation_therapy_9|Radiation therapy]]
+|style="background-color:#00CD00"|Superior DFS
 |-
-|[http://jco.ascopubs.org/content/12/2/385.long Taylor et al. 1994]
+|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(16)30410-7/fulltext Sun et al. 2016]
 |style="background-color:#00CD00"|Phase III
-|[[#Cisplatin.2C_Fluorouracil_.28PF.29.2C_concurrent_RT|Cisplatin, 5-FU, RT]]
+|[[#TPF_-.3E_Cisplatin_.26_RT|TPF -> Cisplatin & RT]]
+|style="background-color:#ff0000"|Seems to have inferior FFS
 |-
 |}
+====Chemoradiotherapy====
+*[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV once per day on days 1, 22, 43
+*Concurrent radiation therapy as follows:
+**'''Adelstein et al. 2003''' and '''RTOG 91-11''': 2 Gy fractions x 35 fractions (total dose: 70 Gy), given 5 times per week over 7 weeks
+**'''Sun et al. 2016''': see paper for details
-====Chemotherapy====
+'''One course'''
-*[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV over 15 minutes once on day 1
-*[[Fluorouracil (5-FU)]] 1000 mg/m<sup>2</sup>/day IV continuous infusion over 120 hours on days 1 to 5 (total dose per cycle: 5000 mg/m<sup>2</sup>)
-'''21-day cycle for 3 cycles, followed by:'''
+===Regimen #2 {{#subobject:b44282|Variant=1}}===
-====Radiotherapy====
-*Radiation therapy, 1.8 to 2 Gy fractions to a total dose of 70 Gy, given 5 times per week over 7 to 8 weeks
-===Regimen #3 {{#subobject:de6fdb|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
-|[http://jnci.oxfordjournals.org/content/101/7/498.long Pointreau et al. 2009 (GORTEC)]
+|[http://jco.ascopubs.org/content/32/27/2940.long Ang et al. 2014 (RTOG 0522)]
 |style="background-color:#00CD00"|Phase III
-|[[#Cisplatin.2C_Fluorouracil.2C_Docetaxel_.28DCF.2C_TPF.29_-.3E_sequential_RT|TPF -> RT]]
+|Cetuximab, Cisplatin, RT
+|style="background-color:#eeee00"|Seems not superior
 |-
 |}
+====Chemoradiotherapy====
+*[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV once per day on days 1 & 22
+*Concurrent radiation therapy by one of the following:
+**IMRT: 2 Gy fractions x 35 fractions (total dose: 70 Gy), given 6 times per week over 6 weeks
+**Accelerated radiotherapy: 42 fractions (total dose: 72 Gy), given twice per day for 12 days then once per day over 6 weeks
-====Chemotherapy====
+'''One course'''
-*[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV over 1 hour once on day 1
-*[[Fluorouracil (5-FU)]] 1000 mg/m<sup>2</sup>/day IV continuous infusion over 5 days on days 1 to 5 (total dose per cycle: 5000 mg/m<sup>2</sup>)
-====Supportive medications====
+===Regimen #3 {{#subobject:b41045|Variant=1}}===
-*Normal saline (use of mannitol, KCl, and magnesium sulfate per institutional protocol) 1000 mL IV given twice, before and after cisplatin
+{| border="1" style="text-align:center;" !align="left"
+|'''Study'''
-'''21-day cycle for 3 cycles'''
-''Patients who responded to induction chemotherapy proceeded to radiation therapy within 3 to 7 weeks of finishing chemotherapy. Patients who did not respond to induction chemotherapy proceeded to surgery and postoperative radiotherapy (see Pointreau et al. 2009 for details).''
-====Radiotherapy====
-*Radiation therapy to the primary tumor and involved lymph nodes, 2 Gy fractions x 35 fractions (total dose: 70 Gy), given 5 times per week over 7 weeks. Prophylactic radiation to the volume at risk for microscopic disease, 2 Gy fractions x 25 to 27 fractions (total dose: 50 to 54 Gy), given 5 times per week.
-*"Chemotherapy (cisplatin, carboplatin, and 5-fluorouracil or a combination of two drugs) during radiotherapy was allowed for all patients who were treated at the same institute, according to its practice." No further details available.
-===Regimen #4 {{#subobject:23fcf5|Variant=1}}===
-{| border="1" style="text-align:center;" !align="left"
-|'''Study'''
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
-|[http://www.nejm.org/doi/full/10.1056/NEJMoa071028 Vermorken et al. 2007 (EORTC 24971/TAX 323)]
+|[http://jnci.oxfordjournals.org/content/97/7/536.long Chan et al. 2005]
 |style="background-color:#00CD00"|Phase III
-|[[#Cisplatin.2C_Fluorouracil.2C_Docetaxel_.28DCF.2C_TPF.29_-.3E_sequential_RT|TPF -> RT]]
+|[[#Radiation_therapy_9|Radiation therapy]]
+|style="background-color:#00CD00"|Might have superior OS
 |-
 |}
-====Chemotherapy====
-*[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV over 1 hour once on day 1, '''given first before fluorouracil'''
-*[[Fluorouracil (5-FU)]] 1000 mg/m<sup>2</sup>/day IV continuous infusion over 5 days on days 1 to 5 (total dose per cycle: 5000 mg/m<sup>2</sup>)
-====Supportive medications====
+''This study only involved patients with locoregionally advanced nasopharyngeal carcinoma.''
-*"Adequate [[Antiemesis|antiemetic]] medications during chemotherapy"
+====Chemoradiotherapy====
-*Prophylactic [[Filgrastim (Neupogen)|granulocyte colony-stimulating factor]] only allowed for patients who had "febrile neutropenia or infection, a delay in recovery of the absolute neutrophil count at day 28, or grade 4 neutropenia persisting for 7 days or more."
+*[[Cisplatin (Platinol)]] 40 mg/m<sup>2</sup> in 1 liter normal saline IV over 2 hours once per day on days 1, 8, 15, 22, 29, 36, 43
+*Concurrent radiation therapy, 2 Gy fractions x 33 fractions (total dose: 66 Gy), given 5 times per week over 6.5 weeks. See Chan et al. 2005 for additional information about boost doses.
-'''21-day cycle for 4 cycles'''
+'''One course'''
-''Patients without progressive disease and who had recovery of marrow function, resolution of mucositis, and healed from any dental procedures started radiation therapy within 4 to 7 weeks of finishing chemotherapy:''
-====Radiotherapy====
-*Radiation therapy over 7 weeks with one of the following (further details not provided):
-**Conventional fractionation, total dose 66 to 70 Gy
-**Accelerated fractionation, total dose 70 Gy
-**Hyperfractionated, total dose 74 Gy
 ===References===
-# Taylor SG 4th, Murthy AK, Vannetzel JM, Colin P, Dray M, Caldarelli DD, Shott S, Vokes E, Showel JL, Hutchinson JC et al. Randomized comparison of neoadjuvant cisplatin and fluorouracil infusion followed by radiation versus concomitant treatment in advanced head and neck cancer. J Clin Oncol. 1994 Feb;12(2):385-95. [http://jco.ascopubs.org/content/12/2/385.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/8113846 PubMed]
+# Adelstein DJ, Li Y, Adams GL, Wagner H Jr, Kish JA, Ensley JF, Schuller DE, Forastiere AA. 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 Jan 1;21(1):92-8. [http://jco.ascopubs.org/content/21/1/92.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12506176 PubMed]
-# Forastiere AA, Goepfert H, Maor M, Pajak TF, Weber R, Morrison W, Glisson B, Trotti A, Ridge JA, Chao C, Peters G, Lee DJ, Leaf A, Ensley J, Cooper J. Concurrent chemotherapy and radiotherapy for organ preservation in advanced laryngeal cancer. N Engl J Med. 2003 Nov 27;349(22):2091-8. [http://www.nejm.org/doi/full/10.1056/NEJMoa031317 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/14645636 PubMed]
+# Forastiere AA, Goepfert H, Maor M, Pajak TF, Weber R, Morrison W, Glisson B, Trotti A, Ridge JA, Chao C, Peters G, Lee DJ, Leaf A, Ensley J, Cooper J. Concurrent chemotherapy and radiotherapy for organ preservation in advanced laryngeal cancer. N Engl J Med. 2003 Nov 27;349(22):2091-8. [http://www.nejm.org/doi/full/10.1056/NEJMoa031317 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/14645636 PubMed]
-## '''Update:''' Forastiere AA, Zhang Q, Weber RS, Maor MH, Goepfert H, Pajak TF, Morrison W, Glisson B, Trotti A, Ridge JA, Thorstad W, Wagner H, Ensley JF, Cooper JS. Long-term results of RTOG 91-11: a comparison of three nonsurgical treatment strategies to preserve the larynx in patients with locally advanced larynx cancer. J Clin Oncol. 2013 Mar 1;31(7):845-52. Epub 2012 Nov 26. [http://jco.ascopubs.org/content/31/7/845.long link to original article] '''contains partial protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/23182993 PubMed]
+## '''Update:''' Forastiere AA, Zhang Q, Weber RS, Maor MH, Goepfert H, Pajak TF, Morrison W, Glisson B, Trotti A, Ridge JA, Thorstad W, Wagner H, Ensley JF, Cooper JS. Long-term results of RTOG 91-11: a comparison of three nonsurgical treatment strategies to preserve the larynx in patients with locally advanced larynx cancer. J Clin Oncol. 2013 Mar 1;31(7):845-52. Epub 2012 Nov 26. [http://jco.ascopubs.org/content/31/7/845.long link to original article] '''contains partial protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23182993 PubMed]
-# Vermorken JB, Remenar E, van Herpen C, Gorlia T, Mesia R, Degardin M, Stewart JS, Jelic S, Betka J, Preiss JH, van den Weyngaert D, Awada A, Cupissol D, Kienzer HR, Rey A, Desaunois I, Bernier J, Lefebvre JL; EORTC 24971/TAX 323 Study Group. Cisplatin, fluorouracil, and docetaxel in unresectable head and neck cancer. N Engl J Med. 2007 Oct 25;357(17):1695-704. [http://www.nejm.org/doi/full/10.1056/NEJMoa071028 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/17960012 PubMed]
+# Chan AT, Leung SF, Ngan RK, Teo PM, Lau WH, Kwan WH, Hui EP, Yiu HY, Yeo W, Cheung FY, Yu KH, Chiu KW, Chan DT, Mok TS, Yau S, Yuen KT, Mo FK, Lai MM, Ma BB, Kam MK, Leung TW, Johnson PJ, Choi PH, Zee BC. Overall survival after concurrent cisplatin-radiotherapy compared with radiotherapy alone in locoregionally advanced nasopharyngeal carcinoma. J Natl Cancer Inst. 2005 Apr 6;97(7):536-9. [http://jnci.oxfordjournals.org/content/97/7/536.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/15812080 PubMed]
-## '''QoL Analysis:''' van Herpen CM, Mauer ME, Mesia R, Degardin M, Jelic S, Coens C, Betka J, Bernier J, Remenar E, Stewart JS, Preiss JH, van den Weyngaert D, Bottomley A, Vermorken JB; EORTC Head and Neck Group. Short-term health-related quality of life and symptom control with docetaxel, cisplatin, 5-fluorouracil and cisplatin (TPF), 5-fluorouracil (PF) for induction in unresectable locoregionally advanced head and neck cancer patients (EORTC 24971/TAX 323). Br J Cancer. 2010 Oct 12;103(8):1173-81. Epub 2010 Sep 14. [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2967049/ link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/20842129 PubMed]
+# Ang KK, Zhang Q, Rosenthal DI, Nguyen-Tan PF, Sherman EJ, Weber RS, Galvin JM, Bonner JA, Harris J, El-Naggar AK, Gillison ML, Jordan RC, Konski AA, Thorstad WL, Trotti A, Beitler JJ, Garden AS, Spanos WJ, Yom SS, Axelrod RS. Randomized phase III trial of concurrent accelerated radiation plus cisplatin with or without cetuximab for stage III to IV head and neck carcinoma: RTOG 0522. J Clin Oncol. 2014 Sep 20;32(27):2940-50. [http://jco.ascopubs.org/content/32/27/2940.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25154822 PubMed]
-# Pointreau Y, Garaud P, Chapet S, Sire C, Tuchais C, Tortochaux J, Faivre S, Guerrif S, Alfonsi M, Calais G. Randomized trial of induction chemotherapy with cisplatin and 5-fluorouracil with or without docetaxel for larynx preservation. J Natl Cancer Inst. 2009 Apr 1;101(7):498-506. Epub 2009 Mar 24. [http://jnci.oxfordjournals.org/content/101/7/498.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/19318632 PubMed]
+# Sun Y, Li WF, Chen NY, Zhang N, Hu GQ, Xie FY, Sun Y, Chen XZ, Li JG, Zhu XD, Hu CS, Xu XY, Chen YY, Hu WH, Guo L, Mo HY, Chen L, Mao YP, Sun R, Ai P, Liang SB, Long GX, Zheng BM, Feng XL, Gong XC, Li L, Shen CY, Xu JY, Guo Y, Chen YM, Zhang F, Lin L, Tang LL, Liu MZ, Ma J. Induction chemotherapy plus concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: a phase 3, multicentre, randomised controlled  trial. Lancet Oncol. 2016 Sep 26. [Epub ahead of print] [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(16)30410-7/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/27686945 PubMed]
-==Cisplatin & Fluorouracil (PF) -> Carboplatin & concurrent RT {{#subobject:b5390f|Regimen=1}}==
+==Cisplatin & RT -> CF {{#subobject:94720|Regimen=1}}==
 {| class="wikitable" style="float:right; margin-left: 5px;"
 |-
 |[[#top|back to top]]
 |}
-PF: '''<u>P</u>'''latinol (Cisplatin), '''<u>F</u>'''luorouracil
+Cisplatin & RT -> CF: Cisplatin and '''<u>R</u>'''adiation '''<u>T</u>'''herapy followed by '''<u>C</u>'''isplatin and '''<u>F</u>'''luorouracil
-===Regimen {{#subobject:37c90b|Variant=1}}===
+===Regimen #1 {{#subobject:e1c43a|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
-|[http://www.nejm.org/doi/full/10.1056/NEJMoa070956 Posner et al. 2007 (TAX 324)]
+|[http://jco.ascopubs.org/content/16/4/1310.long Al-Sarraf et al. 1998 (Intergroup 0099)]
 |style="background-color:#00CD00"|Phase III
-|[[#Cisplatin.2C_Fluorouracil.2C_Docetaxel_.28DCF.2C_TPF.29_-.3E_Carboplatin_.26_concurrent_RT|TPF -> Carboplatin & RT]]
+|[[Head_and_neck_cancer#Radiation_therapy_9|Radiation therapy]]
+|style="background-color:#00CD00"|Superior OS
 |-
 |}
-====Chemotherapy====
+''This study only involved patients with stage III and IV nasopharynx cancers without evidence of metastases.''
-*[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV over 30 to 180 minutes once on day 1, '''given first'''
-*[[Fluorouracil (5-FU)]] 1000 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours on days 1 to 4 (total dose per cycle: 4000 mg/m<sup>2</sup>)
-'''21-day cycle for 3 cycles; then start chemoradiotherapy 3 to 8 weeks after the start of cycle 3:'''
 ====Chemoradiotherapy====
-*[[Carboplatin (Paraplatin)]] AUC 1.5 IV over 1 hour once per day on days 1, 8, 15, 22, 29, 36, 43
+*[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV over 15 to 20 minutes once per day on days 1, 22, 43
-*Concurrent radiation therapy, 2 Gy fractions x 35 to 37 fractions (total dose: 70 to 74 Gy), given 5 times per week over 7 to 7.5 weeks
+*Concurrent radiation therapy to the primary tumor, 1.8 to 2 Gy fractions x 35 to 39 fractions (total dose: 70 Gy), given 5 times per week. Minimum total dose to neck nodes is 50 Gy for N0 disease; 66 Gy for nodes =2 cm in size; 70 Gy for nodes >2 cm.
-'''7 to 7.5-week course;''' surgery "performed 6 to 12 weeks after completion of chemoradiotherapy for patients who had an initial nodal stage of N2 and a partial response to induction chemotherapy, N3 disease, or residual disease after chemoradiotherapy."
+====Supportive medications====
+*Forced hydration: 5% dextrose in 1/2 normal saline with 40 mEq KCl, 2000 mL IV continuous infusion over 24 hours given twice, before each dose of [[Cisplatin (Platinol)]] and after the second mannitol infusion
+*Mannitol 12.5 g IV bolus prior to [[Cisplatin (Platinol)]]
+*5% dextrose in 1/2 normal saline with 30 mEq KCl and mannitol 25 g, 1000 mL IV over 4 hours immediately after [[Cisplatin (Platinol)]]
+*[[Antiemesis|Antiemetic]] such as [[Prochlorperazine (Compazine)]] 25 mg rectal suppository given 30 minutes prior to [[Cisplatin (Platinol)]]; [[Prochlorperazine (Compazine)]] 10 mg IM every 4 hours as needed for nausea after [[Cisplatin (Platinol)]]
+'''7 to 8-week course, followed 4 weeks after the last dose of cisplatin used in Chemoradiotherapy by:'''
+====Chemotherapy====
+*[[Cisplatin (Platinol)]] 80 mg/m<sup>2</sup> IV over 15 to 20 minutes once on day 1
+*[[Fluorouracil (5-FU)]] 1000 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours on days 1 to 4 (total dose per cycle: 4000 mg/m<sup>2</sup>)
-===References===
+====Supportive medications====
-# Posner MR, Hershock DM, Blajman CR, Mickiewicz E, Winquist E, Gorbounova V, Tjulandin S, Shin DM, Cullen K, Ervin TJ, Murphy BA, Raez LE, Cohen RB, Spaulding M, Tishler RB, Roth B, Viroglio Rdel C, Venkatesan V, Romanov I, Agarwala S, Harter KW, Dugan M, Cmelak A, Markoe AM, Read PW, Steinbrenner L, Colevas AD, Norris CM Jr, Haddad RI; TAX 324 Study Group. Cisplatin and fluorouracil alone or with docetaxel in head and neck cancer. N Engl J Med. 2007 Oct 25;357(17):1705-15. [http://www.nejm.org/doi/full/10.1056/NEJMoa070956 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/17960013 PubMed]
+*Al-Sarraf et al. 1998 did not specifically say whether the same hydration and antiemetics were used for this chemotherapy as in Chemoradiotherapy.
-==Cisplatin & Fluorouracil (PF) -> Cisplatin & concurrent RT {{#subobject:c0e730|Regimen=1}}==
+'''28-day cycle for 3 cycles'''
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
-PF: '''<u>P</u>'''latinol (Cisplatin), '''<u>F</u>'''luorouracil
-===Regimen {{#subobject:fdece8|Variant=1}}===
+===Regimen #2 {{#subobject:2437a0|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
-|[http://jco.ascopubs.org/content/23/34/8636.long Hitt et al. 2005]
+|[http://www.ejcancer.com/article/S0959-8049%2807%2900262-6/abstract Chitapanarux et al. 2007]
 |style="background-color:#00CD00"|Phase III
-|[[#Cisplatin.2C_Fluorouracil.2C_Paclitaxel_.28PCF.2C_PPF.29_-.3E_Cisplatin_.26_concurrent_RT|PCF -> Cisplatin & RT]]
+|[[Head_and_neck_cancer#Carboplatin_.26_RT_-.3E_Carboplatin_.26_Fluorouracil|Carboplatin & RT -> Carboplatin & 5-FU]]
+|style="background-color:#eeee00"|Seems not superior
 |-
 |}
-====Chemotherapy====
+''This study only involved patients with locoregionally advanced nasopharyngeal carcinoma.''
-*[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV once on day 1
-*[[Fluorouracil (5-FU)]] 1000 mg/m<sup>2</sup>/day IV continuous infusion over 5 days on days 1 to 5 (total dose per cycle: 5000 mg/m<sup>2</sup>)
-'''3-week cycle for 3 cycles'''
+====Chemoradiotherapy====
+*[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV over 3 hours once per day on days 1, 22, 43
+*Concurrent radiation therapy to the primary tumor, 2 Gy fractions x 35 fractions (total dose: 70 Gy), given 5 times per week over 7 weeks
+'''7-week course, followed 4 weeks after the end of radiation therapy by:'''
-''Patients then undergo ENT evaluation and CT imaging of the primary tumor and neck. Patients with complete response (CR) or partial response of >80% in the primary tumor and no evidence of progression in neck lymph nodes proceeded to chemoradiotherapy. "Patients with a PR of less than 80% or stable disease in the neck lymph nodes (especially if N2 or N3 disease) after induction CT were referred to surgery for neck dissection, if the surgeons were in agreement, before the administration of CRT." Patients with no response or progression of disease were taken off study.''
+====Chemotherapy====
+*[[Cisplatin (Platinol)]] 80 mg/m<sup>2</sup> IV once on day 1
+*[[Fluorouracil (5-FU)]] 1000 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours on days 1 to 4 (total dose per cycle: 4000 mg/m<sup>2</sup>)
-====Chemoradiotherapy====
+'''28-day cycle for 3 cycles'''
-*[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV once per day on days 1, 22, 43
-*Concurrent radiation therapy to primary tumor, 2 Gy fractions x 35 fractions (total dose: 70 Gy), given 5 times per week over 7 weeks. Nodal areas not involved by tumor received 50 Gy.
 ===References===
-# Hitt R, López-Pousa A, Martínez-Trufero J, Escrig V, Carles J, Rizo A, Isla D, Vega ME, Martí JL, Lobo F, Pastor P, Valentí V, Belón J, Sánchez MA, Chaib C, Pallarés C, Antón A, Cervantes A, Paz-Ares L, Cortés-Funes H. 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 Dec 1;23(34):8636-45. Epub 2005 Nov 7. [http://jco.ascopubs.org/content/23/34/8636.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/16275937 PubMed]
+# Al-Sarraf M, LeBlanc M, Giri PG, Fu KK, Cooper J, Vuong T, Forastiere AA, Adams G, Sakr WA, Schuller DE, Ensley JF. Chemoradiotherapy versus radiotherapy in patients with advanced nasopharyngeal cancer: phase III randomized Intergroup study 0099. J Clin Oncol. 1998 Apr;16(4):1310-7. [http://jco.ascopubs.org/content/16/4/1310.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/9552031 PubMed]
+# Chitapanarux I, Lorvidhaya V, Kamnerdsupaphon P, Sumitsawan Y, Tharavichitkul E, Sukthomya V, Ford J. Chemoradiotherapy comparing cisplatin versus carboplatin in locally advanced nasopharyngeal cancer: randomised, non-inferiority, open trial. Eur J Cancer. 2007 Jun;43(9):1399-406. Epub 2007 Apr 27. [http://www.ejcancer.com/article/S0959-8049%2807%2900262-6/abstract link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/17467265 PubMed]
-==Cisplatin, Fluorouracil, Docetaxel (DCF, TPF) -> Carboplatin & concurrent RT {{#subobject:b86d78|Regimen=1}}==
+==Cisplatin, Paclitaxel, RT {{#subobject:d482cc|Regimen=1}}==
 {| class="wikitable" style="float:right; margin-left: 5px;"
 |-
 |[[#top|back to top]]
 |}
-DCF: '''<u>D</u>'''ocetaxel, '''<u>C</u>'''isplatin, '''<u>F</u>'''luorouracil
+RT: '''<u>R</u>'''adiation '''<u>T</u>'''herapy
-<br>TPF: '''<u>T</u>'''axotere (Docetaxel), '''<u>P</u>'''latinol (Cisplatin), '''<u>F</u>'''luorouracil
+===Regimen {{#subobject:6f799d|Variant=1}}===
-===Regimen {{#subobject:3c426b|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
+|-
+|rowspan=2|[http://jco.ascopubs.org/content/22/14/2856.long Garden et al. 2004 (RTOG 97-03)]
+|rowspan=2 style="background-color:#00CD00"|Randomized Phase II
+|[[#CF_.26_RT|CF & RT]]
+|style="background-color:#eeee00"|Seems not superior
 |-
-|[http://www.nejm.org/doi/full/10.1056/NEJMoa070956 Posner et al. 2007 (TAX 324)]
+|[[#Fluorouracil.2C_Hydroxyurea.2C_RT|5-FU, Hydroxyurea, RT]]
-|style="background-color:#00CD00"|Phase III
+|style="background-color:#eeee00"|Seems not superior
-|[[#Cisplatin_.26_Fluorouracil_.28PF.29_-.3E_Carboplatin_.26_concurrent_RT|PF -> Carboplatin & RT]]
 |-
 |}
-====Chemotherapy====
-*[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV over 1 hour once on day 1, '''given first before cisplatin'''
-*[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV over 30 to 180 minutes once on day 1, '''given second after docetaxel'''
-*[[Fluorouracil (5-FU)]] 1000 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours on days 1 to 4, '''given third''' (total dose per cycle: 4000 mg/m<sup>2</sup>)
-====Supportive medications====
-*[[Dexamethasone (Decadron)]] used (dose, route, schedule not specified) to prevent docetaxel-related side effects
-*Prophylactic antibiotics (further details not given) on days 5 to 14
-*Prophylactic [[Filgrastim (Neupogen)|granulocyte colony-stimulating factor]] not allowed
-'''21-day cycle for 3 cycles; then start chemoradiotherapy 3 to 8 weeks after the start of cycle 3:'''
 ====Chemoradiotherapy====
-*[[Carboplatin (Paraplatin)]] AUC 1.5 IV over 1 hour once per day on days 1, 8, 15, 22, 29, 36, 43
+*[[Cisplatin (Platinol)]] 20 mg/m<sup>2</sup> IV once each Tuesday on weeks 1 to 7, given prior to radiation
-*Concurrent radiation therapy, 2 Gy fractions x 35 to 37 fractions (total dose: 70 to 74 Gy), given 5 times per week over 7 to 7.5 weeks
+*[[Paclitaxel (Taxol)]] 30 mg/m<sup>2</sup> IV once each Monday on weeks 1 to 7, given prior to radiation
+*Concurrent radiation therapy, 2 Gy fractions x 35 fractions (total dose: 70 Gy), given 5 times per week over 7 weeks
-'''7 to 7.5-week course;''' surgery "performed 6 to 12 weeks after completion of chemoradiotherapy for patients who had an initial nodal stage of N2 and a partial response to induction chemotherapy, N3 disease, or residual disease after chemoradiotherapy."
+'''7-week course of therapy'''
 ===References===
-# Posner MR, Hershock DM, Blajman CR, Mickiewicz E, Winquist E, Gorbounova V, Tjulandin S, Shin DM, Cullen K, Ervin TJ, Murphy BA, Raez LE, Cohen RB, Spaulding M, Tishler RB, Roth B, Viroglio Rdel C, Venkatesan V, Romanov I, Agarwala S, Harter KW, Dugan M, Cmelak A, Markoe AM, Read PW, Steinbrenner L, Colevas AD, Norris CM Jr, Haddad RI; TAX 324 Study Group. Cisplatin and fluorouracil alone or with docetaxel in head and neck cancer. N Engl J Med. 2007 Oct 25;357(17):1705-15. [http://www.nejm.org/doi/full/10.1056/NEJMoa070956 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/17960013 PubMed]
+# Garden AS, Harris J, Vokes EE, Forastiere AA, Ridge JA, Jones C, Horwitz EM, Glisson BS, Nabell L, Cooper JS, Demas W, Gore E. Preliminary results of Radiation Therapy Oncology Group 97-03: a randomized phase ii trial of concurrent radiation and chemotherapy for advanced squamous cell carcinomas of the head and neck. J Clin Oncol. 2004 Jul 15;22(14):2856-64. [http://jco.ascopubs.org/content/22/14/2856.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/15254053 PubMed]
-==Cisplatin, Fluorouracil, Docetaxel (DCF, TPF) -> Cisplatin & concurrent RT {{#subobject:6d2604|Regimen=1}}==
+==Fluorouracil, Hydroxyurea, RT {{#subobject:3f664e|Regimen=1}}==
 {| class="wikitable" style="float:right; margin-left: 5px;"
 |-
 |[[#top|back to top]]
 |}
-DCF: '''<u>D</u>'''ocetaxel, '''<u>C</u>'''isplatin, '''<u>F</u>'''luorouracil
+RT: '''<u>R</u>'''adiation '''<u>T</u>'''herapy
-<br>TPF: '''<u>T</u>'''axotere, '''<u>P</u>'''latinol, '''<u>F</u>'''luorouracil
+===Regimen {{#subobject:892cec|Variant=1}}===
-===Regimen #1 {{#subobject:19b8a3|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
@@ Line 738: / Line 774: @@
 |[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
-|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(16)30410-7/fulltext Sun et al. 2016]
+|rowspan=2|[http://jco.ascopubs.org/content/22/14/2856.long Garden et al. 2004 (RTOG 97-03)]
-|style="background-color:#00cd00"|Phase III
+|rowspan=2 style="background-color:#00CD00"|Randomized Phase II
-|[[#Cisplatin_.26_concurrent_RT_2|Cisplatin & concurrent RT]]
+|[[#CF_.26_RT|CF & RT]]
-|style="background-color:#00cd00"|Seems to have superior FFS
+|style="background-color:#eeee00"|Seems not superior
+|-
+|[[#Cisplatin.2C_Paclitaxel.2C_RT|Cisplatin, Paclitaxel, RT]]
+|style="background-color:#eeee00"|Seems not superior
 |-
 |}
-====Chemotherapy====
+====Chemoradiotherapy====
-*[[Docetaxel (Taxotere)]] 60 mg/m<sup>2</sup> IV once on day 1
+*[[Fluorouracil (5-FU)]] 800 mg/m<sup>2</sup>/day IV continuous infusion given 5 days per week on weeks 1, 3, 5, 7, 9, 11, 13 (total dose per week: 4000 mg/m<sup>2</sup>)
-*[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV once on day 1
+**''Note: Garden et al. 2004 was not clear about the exact schedule nor duration of the continuous infusion, such as whether each continuous infusion was over 24 hours or not''
-*[[Fluorouracil (5-FU)]] 600 mg/m<sup>2</sup>/day IV continuous infusion over 120 hours on days 1 to 5 (total dose per cycle: 3000 mg/m<sup>2</sup>)
+*[[Hydroxyurea (Hydrea)]] 1000 mg PO every 12 hours x 11 doses per week on weeks 1, 3, 5, 7, 9, 11, 13 (total dose per week: 11,000 mg)
+**''Note: Garden et al. 2004 did not clearly specify when the doses of hydroxyurea were to be taken in relation to radiation treatments''
+*Concurrent radiation therapy, 2 Gy fractions x 35 fractions (total dose: 70 Gy), given 5 times per week on weeks 1, 3, 5, 7, 9, 11, 13
-'''21-day cycle for 3 cycles, followed by:'''
+'''13-week course of therapy'''
-====Chemoradiotherapy====
+===References===
-*[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV once per day on days 1, 22, 43
+# Garden AS, Harris J, Vokes EE, Forastiere AA, Ridge JA, Jones C, Horwitz EM, Glisson BS, Nabell L, Cooper JS, Demas W, Gore E. Preliminary results of Radiation Therapy Oncology Group 97-03: a randomized phase ii trial of concurrent radiation and chemotherapy for advanced squamous cell carcinomas of the head and neck. J Clin Oncol. 2004 Jul 15;22(14):2856-64. [http://jco.ascopubs.org/content/22/14/2856.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/15254053 PubMed]
-*Concurrent radiation therapy, see paper for details
-'''One course'''
+==PCF -> Cisplatin & RT {{#subobject:747f5e|Regimen=1}}==
+{| class="wikitable" style="float:right; margin-left: 5px;"
-===Regimen #2 {{#subobject:5a590d|Variant=1}}===
+|-
+|[[#top|back to top]]
+|}
+PCF: '''<u>P</u>'''aclitaxel, '''<u>C</u>'''isplatin, '''<u>F</u>'''luorouracil
+<br>PPF: '''<u>P</u>'''aclitaxel, '''<u>P</u>'''latinol (Cisplatin), '''<u>F</u>'''luorouracil
+<br>RT: '''<u>R</u>'''adiation '''<u>T</u>'''herapy
+===Regimen {{#subobject:2d319e|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
-|[http://jco.ascopubs.org/content/31/7/853.long Lefebvre et al. 2013 (TREMPLIN)]
+|[http://jco.ascopubs.org/content/23/34/8636.long Hitt et al. 2005]
-|style="background-color:#00cd00"|Randomized Phase II
+|style="background-color:#00CD00"|Phase III
-|TPF -> Cetuximab & RT
+|[[#CF_-.3E_Cisplatin_.26_RT|CF -> Cisplatin & RT]]
+|style="background-color:#00CD00"|Superior CR rate
 |-
 |}
 ====Chemotherapy====
-*[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV once on day 1
+*[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV over 3 hours once on day 1
-*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV once on day 1
+*[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV once on day 2
-*[[Fluorouracil (5-FU)]] 750 mg/m<sup>2</sup> IV once per day on days 1 to 5 (total dose per cycle: 3750 mg/m<sup>2</sup>)
+*[[Fluorouracil (5-FU)]] 500 mg/m<sup>2</sup>/day IV continuous infusion over 5 days on days 2 to 6 (total dose per cycle: 2500 mg/m<sup>2</sup>)
 ====Supportive medications====
-*"Hydration was delivered according to institutional protocols."
+*"Standard intravenous premedications with [[Dexamethasone (Decadron)]], [[Diphenhydramine (Benadryl)]], and [[Cimetidine (Tagamet)]] or [[Ranitidine (Zantac)]] were administered 30 minutes before [[Paclitaxel (Taxol)]] infusion to prevent hypersensitivity reactions."
-*[[Dexamethasone (Decadron)]] 8 mg PO BID the day before, the day of, and day after [[Docetaxel (Taxotere)]]
-*Ciprofloxacin (Cipro) 500 mg PO BID on days 5 to 15
-*Prophylactic [[Filgrastim (Neupogen)|granulocyte colony-stimulating factor]] was not used. [[Filgrastim (Neupogen)|G-CSF]] 150 mcg/m<sup>2</sup> SC once per day was used if febrile neutropenia occurred.
-*"Setrons" ([[Antiemesis|5-HT3 antagonists]]) given twice, before and after [[Cisplatin (Platinol)]]
-'''21-day cycle for 3 cycles'''
+'''3-week cycle for 3 cycles'''
-''Restaging of disease takes place 2 weeks after finishing cycle 3. Patients who had "at least 50% regression of their primary tumor volume and who recovered larynx mobility" were treated with Chemoradiotherapy. Patients who did not have at least 50% regression had salvage total laryngectomy.''
+''Patients then undergo ENT evaluation and CT imaging of the primary tumor and neck. Patients with complete response (CR) or partial response of >80% in the primary tumor and no evidence of progression in neck lymph nodes proceeded to chemoradiotherapy. "Patients with a PR of less than 80% or stable disease in the neck lymph nodes (especially if N2 or N3 disease) after induction CT were referred to surgery for neck dissection, if the surgeons were in agreement, before the administration of CRT." Patients with no response or progression of disease were taken off study.''
 ====Chemoradiotherapy====
 *[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV once per day on days 1, 22, 43
-*Concurrent radiation therapy, 2 Gy fractions x 35 fractions (total dose: 70 Gy), given once per day 5 times per week over 7 weeks
+*Concurrent radiation therapy to primary tumor, 2 Gy fractions x 35 fractions (total dose: 70 Gy), given 5 times per week over 7 weeks. Nodal areas not involved by tumor received 50 Gy.
+===References===
+# Hitt R, López-Pousa A, Martínez-Trufero J, Escrig V, Carles J, Rizo A, Isla D, Vega ME, Martí JL, Lobo F, Pastor P, Valentí V, Belón J, Sánchez MA, Chaib C, Pallarés C, Antón A, Cervantes A, Paz-Ares L, Cortés-Funes H. 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 Dec 1;23(34):8636-45. Epub 2005 Nov 7. [http://jco.ascopubs.org/content/23/34/8636.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/16275937 PubMed]
-===Regimen #3 {{#subobject:425bf|Variant=1}}===
+==PCF -> Paclitaxel & RT {{#subobject:efeb5|Regimen=1}}==
+{| class="wikitable" style="float:right; margin-left: 5px;"
+|-
+|[[#top|back to top]]
+|}
+PCF: '''<u>P</u>'''aclitaxel, '''<u>C</u>'''isplatin, '''<u>F</u>'''luorouracil
+<br>PPF: '''<u>P</u>'''aclitaxel, '''<u>P</u>'''latinol, '''<u>F</u>'''luorouracil
+<br>RT: '''<u>R</u>'''adiation '''<u>T</u>'''herapy
+===Regimen {{#subobject:d5e568|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |-
-|[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2967367/ Adelstein et al. 2010 (SWOG S0216)]
+|[http://annonc.oxfordjournals.org/content/13/10/1665.long Hitt et al. 2002]
 |style="background-color:#EEEE00"|Phase II
 |-
@@ Line 799: / Line 854: @@
 ====Chemotherapy====
-*[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV once on day 1
+*[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV over 3 hours once on day 1
-*[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV once on day 1
+*[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV over 1 hour once on day 2
-*[[Fluorouracil (5-FU)]] 1000 mg/m<sup>2</sup>/day IV continuous infusion over 4 days on days 1 to 4 (total dose per cycle: 4000 mg/m<sup>2</sup>)
+*[[Fluorouracil (5-FU)]] 500 mg/m<sup>2</sup>/day IV continuous infusion over 5 days on days 2 to 6 (total dose per cycle: 2500 mg/m<sup>2</sup>)
 ====Supportive medications====
-*Ciprofloxacin (Cipro) prophylaxis for 10 days (dose/route/precise schedule not specified)
+*[[Dexamethasone (Decadron)]] 20 mg IV once 30 minutes prior to [[Paclitaxel (Taxol)]]
-*"Standard anti-emetics, hydration and diuresis"
+*[[Dexamethasone (Decadron)]] 8 mg PO BID on days 2 & 3
+*[[Ondansetron (Zofran)]] 8 mg IV/PO Q8H or Q12H on days 1 to 5
+*[[Diphenhydramine (Benadryl)]] 50 mg IV once 30 minutes prior to [[Paclitaxel (Taxol)]]
+*[[Cimetidine (Tagamet)]] 300 mg IV once 30 minutes prior to [[Paclitaxel (Taxol)]]
+**Per Hitt et al. 2005, [[Ranitidine (Zantac)]] (dose not specified) could be used instead
+*Mannitol and IV hydration with [[Cisplatin (Platinol)]]
-'''21-day cycle for 2 cycles'''
+'''3-week cycle for 3 cycles'''
-''Restaging of disease takes place 3 weeks after finishing cycle 2. Patients with stable or tumors which responded to therapy proceed to concurrent Chemoradiotherapy therapy. Patients with progressive disease are considered--if possible--for surgical resection and post-operative radiation. Patients who could not undergo surgery also received concurrent Chemoradiotherapy therapy.''
+''Patients undergo ENT evaluation and CT imaging of the primary tumor and neck during week 3 or 4 of cycle 3. Patients who did not have at least a partial response were recommended for surgery. Patients with bulky nodal disease prior to therapy "and/or suboptimal response to induction chemotherapy" were recommended for neck dissection before radiation therapy. Surgery was performed 4 weeks after cycle 3 day 1. Patients with complete response (CR) or partial response proceeded to chemoradiotherapy; radiation therapy alone was used "if concomitant treatment was not feasible."''
 ====Chemoradiotherapy====
-*[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV once per day on days 1 & 22
+''Chemoradiotherapy starts 4 to 6 weeks after cycle 3 day 1 or as soon as patients recover from surgery (if any).''
-*Concurrent radiation therapy, 1.8 Gy fractions x 30 fractions, given 5 times per week (total dose: 54 Gy)
+*[[Paclitaxel (Taxol)]] 25 mg/m<sup>2</sup> IV over 1 hour once per week during radiation therapy, starting on day 1
-**The last 12 treatments involved a boost volume, 1.5 Gy fractions x 12 fractions (dose to boost volume: 18 Gy)
+*Concurrent radiation therapy to primary unresected tumors, 1.8 to 2 Gy fractions (total dose: 65 to 70 Gy). Post-operative areas received 60 Gy. Nodal areas not involved by tumor received at least 45 Gy.
 ====Supportive medications====
-*"Standard hydration and anti-emetic therapy"
+*"Usual pre-medication was given before each paclitaxel infusion" (presumably the same ones used during induction chemotherapy).
+===References===
+# Hitt R, Paz-Ares L, Brandáriz A, Castellano D, Peña C, Millán JM, Calvo F, Ortiz de Urbina D, López E, Alvarez-Vicent JJ, Cortés-Funes H. Induction chemotherapy with paclitaxel, cisplatin and 5-fluorouracil for squamous cell carcinoma of the head and neck: long-term results of a phase II trial. Ann Oncol. 2002 Oct;13(10):1665-73. [http://annonc.oxfordjournals.org/content/13/10/1665.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12377658 PubMed]
-'''6-week course;''' "Surgical resection was considered after concomitant chemoradiotherapy for those patients with histologically confirmed residual or recurrent disease at the primary site."
+==Radiation therapy {{#subobject:5ac377|Regimen=1}}==
+{| class="wikitable" style="float:right; margin-left: 5px;"
+|-
+|[[#top|back to top]]
+|}
-===Regimen #4 {{#subobject:2d63b4|Variant=1}}===
+===Regimen {{#subobject:ce3d2d|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
+|'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
-|[http://link.springer.com/article/10.1007%2Fs00280-009-1152-0 Bae et al. 2010]
+|[http://jco.ascopubs.org/content/16/4/1310.long Al-Sarraf et al. 1998 (Intergroup 0099)]
-|style="background-color:#EEEE00"|Phase II
+|style="background-color:#00CD00"|Phase III
+|[[#Cisplatin_.26_RT_-.3E_CF|Cisplatin & RT -> CF]]
+|style="background-color:#ff0000"|Inferior OS
+|-
+|rowspan=2|[http://jco.ascopubs.org/content/21/1/92.long Adelstein et al. 2003]
+|rowspan=2 style="background-color:#00CD00"|Phase III
+|[[#CF_.26_RT|CF & RT]]
+|style="background-color:#eeee00"|Seems not superior
+|-
+|[[#Cisplatin_.26_RT_2|Cisplatin & RT]]
+|style="background-color:#ff0000"|Seems to have inferior OS
+|-
+|rowspan=2|[http://www.nejm.org/doi/full/10.1056/NEJMoa031317 Forastiere et al. 2003 (RTOG 91-11)]
+|rowspan=2 style="background-color:#00CD00"|Phase III
+|[[#CF_-.3E_RT|CF -> RT]]
+|style="background-color:#ff0000"|Seems to have inferior DFS
+|-
+|[[#Cisplatin_.26_RT_2|Cisplatin & RT]]
+|style="background-color:#ff0000"|Inferior DFS
+|-
+|[http://jco.ascopubs.org/content/22/1/69.long Denis et al. 2004 (GORTEC 94-01)]
+|style="background-color:#00CD00"|Phase III
+|[[#Carboplatin.2C_Fluorouracil.2C_RT|Carboplatin, 5-FU, RT]]
+|style="background-color:#ff0000"|Seems to have inferior OS
+|-
+|[http://jnci.oxfordjournals.org/content/97/7/536.long Chan et al. 2005]
+|style="background-color:#00CD00"|Phase III
+|[[#Cisplatin_.26_RT_2|Cisplatin & RT]]
+|style="background-color:#ff0000"|Might have inferior OS
+|-
+|[http://www.nejm.org/doi/full/10.1056/NEJMoa053422 Bonner et al. 2006 (IMCL-9815)]
+|style="background-color:#00CD00"|Phase III
+|[[#Cetuximab_.26_RT|Cetuximab & RT]]
+|style="background-color:#ff0000"|Seems to have inferior OS
+|-
+|rowspan=2|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(11)70346-1/abstract Bourhis et al. 2012 (GORTEC 99-02)]
+|rowspan=2 style="background-color:#00CD00"|Phase III
+|[[#Carboplatin.2C_Fluorouracil.2C_RT|Carboplatin, 5-FU, RT]]
+|style="background-color:#ff0000"|Seems to have inferior PFS
+|-
+|Carboplatin, 5-FU, accelerated concurrent RT
+|style="background-color:#ff0000"|Might have inferior PFS
 |-
 |}
-''This study only involved patients with locoregionally advanced nasopharyngeal cancer.''
+''Used as a comparator arm; included for reference purposes only.''
+===References===
+# Al-Sarraf M, LeBlanc M, Giri PG, Fu KK, Cooper J, Vuong T, Forastiere AA, Adams G, Sakr WA, Schuller DE, Ensley JF. Chemoradiotherapy versus radiotherapy in patients with advanced nasopharyngeal cancer: phase III randomized Intergroup study 0099. J Clin Oncol. 1998 Apr;16(4):1310-7. [http://jco.ascopubs.org/content/16/4/1310.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/9552031 PubMed]
+# Adelstein DJ, Li Y, Adams GL, Wagner H Jr, Kish JA, Ensley JF, Schuller DE, Forastiere AA. 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 Jan 1;21(1):92-8. [http://jco.ascopubs.org/content/21/1/92.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12506176 PubMed]
+# Forastiere AA, Goepfert H, Maor M, Pajak TF, Weber R, Morrison W, Glisson B, Trotti A, Ridge JA, Chao C, Peters G, Lee DJ, Leaf A, Ensley J, Cooper J. Concurrent chemotherapy and radiotherapy for organ preservation in advanced laryngeal cancer. N Engl J Med. 2003 Nov 27;349(22):2091-8. [http://www.nejm.org/doi/full/10.1056/NEJMoa031317 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/14645636 PubMed]
+## '''Update:''' Forastiere AA, Zhang Q, Weber RS, Maor MH, Goepfert H, Pajak TF, Morrison W, Glisson B, Trotti A, Ridge JA, Thorstad W, Wagner H, Ensley JF, Cooper JS. Long-term results of RTOG 91-11: a comparison of three nonsurgical treatment strategies to preserve the larynx in patients with locally advanced larynx cancer. J Clin Oncol. 2013 Mar 1;31(7):845-52. Epub 2012 Nov 26. [http://jco.ascopubs.org/content/31/7/845.long link to original article] '''contains partial protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23182993 PubMed]
+# Denis F, Garaud P, Bardet E, Alfonsi M, Sire C, Germain T, Bergerot P, Rhein B, Tortochaux J, Calais G. Final results of the 94-01 French Head and Neck Oncology and Radiotherapy Group randomized trial comparing radiotherapy alone with concomitant radiochemotherapy in advanced-stage oropharynx carcinoma. J Clin Oncol. 2004 Jan 1;22(1):69-76. Epub 2003 Dec 2. [http://jco.ascopubs.org/content/22/1/69.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/14657228 PubMed]
+# Chan AT, Leung SF, Ngan RK, Teo PM, Lau WH, Kwan WH, Hui EP, Yiu HY, Yeo W, Cheung FY, Yu KH, Chiu KW, Chan DT, Mok TS, Yau S, Yuen KT, Mo FK, Lai MM, Ma BB, Kam MK, Leung TW, Johnson PJ, Choi PH, Zee BC. Overall survival after concurrent cisplatin-radiotherapy compared with radiotherapy alone in locoregionally advanced nasopharyngeal carcinoma. J Natl Cancer Inst. 2005 Apr 6;97(7):536-9. [http://jnci.oxfordjournals.org/content/97/7/536.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/15812080 PubMed]
+# Bonner JA, Harari PM, Giralt J, Azarnia N, Shin DM, Cohen RB, Jones CU, Sur R, Raben D, Jassem J, Ove R, Kies MS, Baselga J, Youssoufian H, Amellal N, Rowinsky EK, Ang KK. Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med. 2006 Feb 9;354(6):567-78. [http://www.nejm.org/doi/full/10.1056/NEJMoa053422 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/16467544 PubMed]
+## '''Update:''' Bonner JA, Harari PM, Giralt J, Cohen RB, Jones CU, Sur RK, Raben D, Baselga J, Spencer SA, Zhu J, Youssoufian H, Rowinsky EK, Ang KK. Radiotherapy plus cetuximab for locoregionally advanced head and neck cancer: 5-year survival data from a phase 3 randomised trial, and relation between cetuximab-induced rash and survival. Lancet Oncol. 2010 Jan;11(1):21-8. Epub 2009 Nov 10. [http://www.sciencedirect.com/science/article/pii/S1470204509703110 link to original article] '''contains partial protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19897418 PubMed]
+## '''QoL Analysis:''' Curran D, Giralt J, Harari PM, Ang KK, Cohen RB, Kies MS, Jassem J, Baselga J, Rowinsky EK, Amellal N, Comte S, Bonner JA. Quality of life in head and neck cancer patients after treatment with high-dose radiotherapy alone or in combination with cetuximab. J Clin Oncol. 2007 Jun 1;25(16):2191-7. [http://jco.ascopubs.org/content/25/16/2191.long link to original article] '''contains partial protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/17538164 PubMed]
+## '''Retrospective subgroup analysis:''' Rosenthal DI, Harari PM, Giralt J, Bell D, Raben D, Liu J, Schulten J, Ang KK, Bonner JA. Association of Human Papillomavirus and p16 Status With Outcomes in the IMCL-9815 Phase III Registration Trial for Patients With Locoregionally Advanced Oropharyngeal Squamous Cell Carcinoma of the Head and Neck Treated With Radiotherapy With or Without Cetuximab. J Clin Oncol. 2016 Apr 20;34(12):1300-8. Epub 2015 Dec 28. [http://jco.ascopubs.org/content/34/12/1300.full link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/26712222 PubMed]
+# Bourhis J, Sire C, Graff P, Grégoire V, Maingon P, Calais G, Gery B, Martin L, Alfonsi M, Desprez P, Pignon T, Bardet E, Rives M, Geoffrois L, Daly-Schveitzer N, Sen S, Tuchais C, Dupuis O, Guerif S, Lapeyre M, Favrel V, Hamoir M, Lusinchi A, Temam S, Pinna A, Tao YG, Blanchard P, Aupérin A. Concomitant chemoradiotherapy versus acceleration of radiotherapy with or without concomitant chemotherapy in locally advanced head and neck carcinoma (GORTEC 99-02): an open-label phase 3 randomised trial. Lancet Oncol. 2012 Feb;13(2):145-53. Epub 2012 Jan 18. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(11)70346-1/abstract link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22261362 PubMed]
-====Chemotherapy====
+==TPF -> Carboplatin & RT {{#subobject:b86d78|Regimen=1}}==
-*[[Docetaxel (Taxotere)]] 70 mg/m<sup>2</sup> in 300 mL normal saline IV over 1 hour once on day 1, '''given first'''
-*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV over 3 hours once on day 1, '''given second'''
-*[[Fluorouracil (5-FU)]] 1000 mg/m<sup>2</sup>/day IV continuous infusion over 4 days on days 1 to 4, '''started after completion of cisplatin''' (total dose per cycle: 4000 mg/m<sup>2</sup>)
-====Supportive medications====
-*[[Dexamethasone (Decadron)]] 20 mg IV once 30 minutes prior to [[Docetaxel (Taxotere)]]
-*Ranitidine (Zantac) 50 mg IV once 30 minutes prior to [[Docetaxel (Taxotere)]]
-*Chlorpheniramine 5 mg IV once 30 minutes prior to [[Docetaxel (Taxotere)]]
-*Posthydration after cisplatin with normal saline (volume/rate not specified)
-*Ondansetron (Zofran) 8 mg IV "was routinely given"
-*Levofloxacin (Levaquin) 500 mg PO once per day on days 5 to 10 as prophylaxis
-*Prophylactic [[Filgrastim (Neupogen)|G-CSF]] per physician's discretion
-'''21-day cycle for 3 cycles; then proceed to chemoradiotherapy:'''
-====Chemoradiotherapy====
-*[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV once per day on days 1 & 22
-*Concurrent radiation therapy, 1.8 to 2 Gy fractions (total dose: 68.4 Gy), given 5 times per week
-===References===
-# Adelstein DJ, Moon J, Hanna E, Giri PG, Mills GM, Wolf GT, Urba SG. 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 Feb;32(2):221-8. [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2967367/ link to PMC article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/19557750 PubMed]
-# Bae WK, Hwang JE, Shim HJ, Cho SH, Lee JK, Lim SC, Chung WK, Chung IJ. Phase II study of docetaxel, cisplatin, and 5-FU induction chemotherapy followed by chemoradiotherapy in locoregionally advanced nasopharyngeal cancer. Cancer Chemother Pharmacol. 2010 Feb;65(3):589-95. [http://link.springer.com/article/10.1007%2Fs00280-009-1152-0 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/19830427 PubMed]
-<!-- Presented as oral presentations at the 45th Annual Meeting of the American Society of Clinical Oncology (ASCO), Orlando, FL, May 29-June 2, 2009, and at the 47th Annual Meeting of ASCO, Chicago, IL, June 3-7, 2011. -->
-# Lefebvre JL, Pointreau Y, Rolland F, Alfonsi M, Baudoux A, Sire C, de Raucourt D, Malard O, Degardin M, Tuchais C, Blot E, Rives M, Reyt E, Tourani JM, Geoffrois L, Peyrade F, Guichard F, Chevalier D, Babin E, Lang P, Janot F, Calais G, Garaud P, Bardet E. Induction chemotherapy followed by either chemoradiotherapy or bioradiotherapy for larynx preservation: the TREMPLIN randomized phase II study. J Clin Oncol. 2013 Mar 1;31(7):853-9. Epub 2013 Jan 22. [http://jco.ascopubs.org/content/31/7/853.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/23341517 PubMed]
-# Sun Y, Li WF, Chen NY, Zhang N, Hu GQ, Xie FY, Sun Y, Chen XZ, Li JG, Zhu XD, Hu CS, Xu XY, Chen YY, Hu WH, Guo L, Mo HY, Chen L, Mao YP, Sun R, Ai P, Liang SB, Long GX, Zheng BM, Feng XL, Gong XC, Li L, Shen CY, Xu JY, Guo Y, Chen YM, Zhang F, Lin L, Tang LL, Liu MZ, Ma J. Induction chemotherapy plus concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: a phase 3, multicentre, randomised controlled  trial. Lancet Oncol. 2016 Sep 26. [Epub ahead of print] [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(16)30410-7/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/27686945 PubMed]
-==Cisplatin, Fluorouracil, Docetaxel (DCF, TPF) -> sequential RT {{#subobject:99e8bb|Regimen=1}}==
 {| class="wikitable" style="float:right; margin-left: 5px;"
 |-
@@ Line 867: / Line 963: @@
 DCF: '''<u>D</u>'''ocetaxel, '''<u>C</u>'''isplatin, '''<u>F</u>'''luorouracil
 <br>TPF: '''<u>T</u>'''axotere (Docetaxel), '''<u>P</u>'''latinol (Cisplatin), '''<u>F</u>'''luorouracil
+<br>RT: '''<u>R</u>'''adiation '''<u>T</u>'''herapy
-===Regimen #1 {{#subobject:6c7d09|Variant=1}}===
+===Regimen {{#subobject:3c426b|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
-|[http://www.nejm.org/doi/full/10.1056/NEJMoa071028 Vermorken et al. 2007 (EORTC 24971/TAX 323)]
+|[http://www.nejm.org/doi/full/10.1056/NEJMoa070956 Posner et al. 2007 (TAX 324)]
 |style="background-color:#00CD00"|Phase III
-|[[#Cisplatin_.26_Fluorouracil_.28PF.29_-.3E_sequential_RT|PF -> RT]]
+|[[#CF_-.3E_Carboplatin_.26_RT|CF -> Carboplatin & RT]]
+|style="background-color:#00CD00"|Superior OS
 |-
 |}
 ====Chemotherapy====
-*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV over 1 hour once on day 1, '''given second after docetaxel'''
-*[[Fluorouracil (5-FU)]] 750 mg/m<sup>2</sup>/day IV continuous infusion over 5 days on days 1 to 5 (total dose per cycle: 3750 mg/m<sup>2</sup>)
 *[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV over 1 hour once on day 1, '''given first before cisplatin'''
+*[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV over 30 to 180 minutes once on day 1, '''given second after docetaxel'''
+*[[Fluorouracil (5-FU)]] 1000 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours on days 1 to 4, '''given third''' (total dose per cycle: 4000 mg/m<sup>2</sup>)
 ====Supportive medications====
-*[[Dexamethasone (Decadron)]] 8 mg PO for 6 doses (exact schedule not specified) starting the night before [[Docetaxel (Taxotere)]]
+*[[Dexamethasone (Decadron)]] used (dose, route, schedule not specified) to prevent [[Docetaxel (Taxotere)]]-related side effects
-*[[Ciprofloxacin (Cipro)]] 500 mg PO BID "or an alternative agent" on days 5 to 15 as prophylaxis
+*Prophylactic antibiotics (further details not given) on days 5 to 14
-*"Adequate [[Antiemesis|antiemetic]] medications during chemotherapy"
+*Prophylactic [[Filgrastim (Neupogen)|granulocyte colony-stimulating factor]] not allowed
-*Prophylactic [[Filgrastim (Neupogen)|granulocyte colony-stimulating factor]] only allowed for patients who had "febrile neutropenia or infection, a delay in recovery of the absolute neutrophil count at day 28, or grade 4 neutropenia persisting for 7 days or more."
+'''21-day cycle for 3 cycles; then start chemoradiotherapy 3 to 8 weeks after the start of cycle 3:'''
-'''21-day cycle for 4 cycles'''
+====Chemoradiotherapy====
+*[[Carboplatin (Paraplatin)]] AUC 1.5 IV over 1 hour once per day on days 1, 8, 15, 22, 29, 36, 43
+*Concurrent radiation therapy, 2 Gy fractions x 35 to 37 fractions (total dose: 70 to 74 Gy), given 5 times per week over 7 to 7.5 weeks
-''Patients without progressive disease and who had recovery of marrow function, resolution of mucositis, and healed from any dental procedures started radiation therapy within 4 to 7 weeks of finishing chemotherapy:''
+'''7 to 7.5-week course;''' surgery "performed 6 to 12 weeks after completion of chemoradiotherapy for patients who had an initial nodal stage of N2 and a partial response to induction chemotherapy, N3 disease, or residual disease after chemoradiotherapy."
-====Radiotherapy====
+===References===
-*Radiation therapy over 7 weeks with one of the following (further details not provided):
+# Posner MR, Hershock DM, Blajman CR, Mickiewicz E, Winquist E, Gorbounova V, Tjulandin S, Shin DM, Cullen K, Ervin TJ, Murphy BA, Raez LE, Cohen RB, Spaulding M, Tishler RB, Roth B, Viroglio Rdel C, Venkatesan V, Romanov I, Agarwala S, Harter KW, Dugan M, Cmelak A, Markoe AM, Read PW, Steinbrenner L, Colevas AD, Norris CM Jr, Haddad RI; TAX 324 Study Group. Cisplatin and fluorouracil alone or with docetaxel in head and neck cancer. N Engl J Med. 2007 Oct 25;357(17):1705-15. [http://www.nejm.org/doi/full/10.1056/NEJMoa070956 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/17960013 PubMed]
-**Conventional fractionation, total dose 66 to 70 Gy
-**Accelerated fractionation, total dose 70 Gy
-**Hyperfractionated, total dose 74 Gy
-===Regimen #2 {{#subobject:e085d0|Variant=1}}===
+==TPF -> Cisplatin & RT {{#subobject:6d2604|Regimen=1}}==
-{| border="1" style="text-align:center;" !align="left"
+{| class="wikitable" style="float:right; margin-left: 5px;"
-|'''Study'''
+|-
+|[[#top|back to top]]
+|}
+DCF: '''<u>D</u>'''ocetaxel, '''<u>C</u>'''isplatin, '''<u>F</u>'''luorouracil
+<br>TPF: '''<u>T</u>'''axotere, '''<u>P</u>'''latinol, '''<u>F</u>'''luorouracil
+<br>RT: '''<u>R</u>'''adiation '''<u>T</u>'''herapy
+===Regimen #1 {{#subobject:19b8a3|Variant=1}}===
+{| border="1" style="text-align:center;" !align="left"
+|'''Study'''
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
-|[http://jnci.oxfordjournals.org/content/101/7/498.long Pointreau et al. 2009 (GORTEC)]
+|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(16)30410-7/fulltext Sun et al. 2016]
-|style="background-color:#00CD00"|Phase III
+|style="background-color:#00cd00"|Phase III
-|[[#Cisplatin_.26_Fluorouracil_.28PF.29_-.3E_sequential_RT|PF -> RT]]
+|[[#Cisplatin_.26_RT_2|Cisplatin & concurrent RT]]
+|style="background-color:#00cd00"|Seems to have superior FFS
 |-
 |}
 ====Chemotherapy====
-*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV over 1 hour once on day 1
+*[[Docetaxel (Taxotere)]] 60 mg/m<sup>2</sup> IV once on day 1
-*[[Fluorouracil (5-FU)]] 750 mg/m<sup>2</sup>/day IV continuous infusion over 5 days on days 1 to 5 (total dose per cycle: 3750 mg/m<sup>2</sup>)
+*[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV once on day 1
-*[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV over 1 hour once on day 1
+*[[Fluorouracil (5-FU)]] 600 mg/m<sup>2</sup>/day IV continuous infusion over 120 hours on days 1 to 5 (total dose per cycle: 3000 mg/m<sup>2</sup>)
-====Supportive medications====
+'''21-day cycle for 3 cycles, followed by:'''
-*Normal saline (use of mannitol, KCl, and magnesium sulfate per institutional protocol) 1000 mL IV given twice, before and after [[Cisplatin (Platinol)]]
-*[[Dexamethasone (Decadron)]] 8 mg PO once per day the day before, the day of, and day after [[Docetaxel (Taxotere)]]
-*[[Ciprofloxacin (Cipro)]] 1000 mg PO (frequency not specified) on days 5 to 15
-*Prophylactic [[Filgrastim (Neupogen)|granulocyte colony-stimulating factor]] not used
-'''21-day cycle for 3 cycles'''
+====Chemoradiotherapy====
+*[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV once per day on days 1, 22, 43
+*Concurrent radiation therapy, see paper for details
-''Patients who responded to induction chemotherapy proceeded to radiation therapy within 3 to 7 weeks of finishing chemotherapy. Patients who did not respond to induction chemotherapy proceeded to surgery and postoperative radiotherapy (see Pointreau et al. 2009 for details).''
+'''One course'''
-====Radiotherapy====
+===Regimen #2 {{#subobject:5a590d|Variant=1}}===
-*Radiation therapy to the primary tumor and involved lymph nodes, 2 Gy fractions x 35 fractions (total dose: 70 Gy), given 5 times per week over 7 weeks. Prophylactic radiation to the volume at risk for microscopic disease, 2 Gy fractions x 25 to 27 fractions (total dose: 50 to 54 Gy), given 5 times per week.
-*"Chemotherapy (cisplatin, carboplatin, and 5-fluorouracil or a combination of two drugs) during radiotherapy was allowed for all patients who were treated at the same institute, according to its practice." No further details available.
-===References===
-# Vermorken JB, Remenar E, van Herpen C, Gorlia T, Mesia R, Degardin M, Stewart JS, Jelic S, Betka J, Preiss JH, van den Weyngaert D, Awada A, Cupissol D, Kienzer HR, Rey A, Desaunois I, Bernier J, Lefebvre JL; EORTC 24971/TAX 323 Study Group. Cisplatin, fluorouracil, and docetaxel in unresectable head and neck cancer. N Engl J Med. 2007 Oct 25;357(17):1695-704. [http://www.nejm.org/doi/full/10.1056/NEJMoa071028 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/17960012 PubMed]
-## '''QoL Analysis:''' van Herpen CM, Mauer ME, Mesia R, Degardin M, Jelic S, Coens C, Betka J, Bernier J, Remenar E, Stewart JS, Preiss JH, van den Weyngaert D, Bottomley A, Vermorken JB; EORTC Head and Neck Group. Short-term health-related quality of life and symptom control with docetaxel, cisplatin, 5-fluorouracil and cisplatin (TPF), 5-fluorouracil (PF) for induction in unresectable locoregionally advanced head and neck cancer patients (EORTC 24971/TAX 323). Br J Cancer. 2010 Oct 12;103(8):1173-81. Epub 2010 Sep 14. [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2967049/ link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/20842129 PubMed]
-# Pointreau Y, Garaud P, Chapet S, Sire C, Tuchais C, Tortochaux J, Faivre S, Guerrif S, Alfonsi M, Calais G. Randomized trial of induction chemotherapy with cisplatin and 5-fluorouracil with or without docetaxel for larynx preservation. J Natl Cancer Inst. 2009 Apr 1;101(7):498-506. Epub 2009 Mar 24. [http://jnci.oxfordjournals.org/content/101/7/498.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/19318632 PubMed] content property of [http://hemonc.org HemOnc.org]
-==Cisplatin, Fluorouracil, Paclitaxel (PCF, PPF) -> Cisplatin & concurrent RT {{#subobject:747f5e|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
-PCF: '''<u>P</u>'''aclitaxel, '''<u>C</u>'''isplatin, '''<u>F</u>'''luorouracil
-<br>PPF: '''<u>P</u>'''aclitaxel, '''<u>P</u>'''latinol (Cisplatin), '''<u>F</u>'''luorouracil
-===Regimen {{#subobject:2d319e|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
-|[http://jco.ascopubs.org/content/23/34/8636.long Hitt et al. 2005]
+|[http://jco.ascopubs.org/content/31/7/853.long Lefebvre et al. 2013 (TREMPLIN)]
-|style="background-color:#00CD00"|Phase III
+|style="background-color:#00cd00"|Randomized Phase II
-|[[#Cisplatin_.26_Fluorouracil_.28PF.29_-.3E_Cisplatin_.26_concurrent_RT|Cisplatin & 5-FU -> Cisplatin & RT]]
+|TPF -> Cetuximab & RT
+|style="background-color:#eeee00"|Seems not superior
 |-
 |}
 ====Chemotherapy====
-*[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV over 3 hours once on day 1
+*[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV once on day 1
-*[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV once on day 2
+*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV once on day 1
-*[[Fluorouracil (5-FU)]] 500 mg/m<sup>2</sup>/day IV continuous infusion over 5 days on days 2 to 6 (total dose per cycle: 2500 mg/m<sup>2</sup>)
+*[[Fluorouracil (5-FU)]] 750 mg/m<sup>2</sup> IV once per day on days 1 to 5 (total dose per cycle: 3750 mg/m<sup>2</sup>)
 ====Supportive medications====
-*"Standard intravenous premedications with dexamethasone, diphenhydramine, and cimetidine or ranitidine were administered 30 minutes before paclitaxel infusion to prevent hypersensitivity reactions."
+*"Hydration was delivered according to institutional protocols."
+*[[Dexamethasone (Decadron)]] 8 mg PO BID the day before, the day of, and day after [[Docetaxel (Taxotere)]]
+*Ciprofloxacin (Cipro) 500 mg PO BID on days 5 to 15
+*Prophylactic [[Filgrastim (Neupogen)|granulocyte colony-stimulating factor]] was not used. [[Filgrastim (Neupogen)|G-CSF]] 150 mcg/m<sup>2</sup> SC once per day was used if febrile neutropenia occurred.
+*"Setrons" ([[Antiemesis|5-HT3 antagonists]]) given twice, before and after [[Cisplatin (Platinol)]]
-'''3-week cycle for 3 cycles'''
+'''21-day cycle for 3 cycles'''
-''Patients then undergo ENT evaluation and CT imaging of the primary tumor and neck. Patients with complete response (CR) or partial response of >80% in the primary tumor and no evidence of progression in neck lymph nodes proceeded to chemoradiotherapy. "Patients with a PR of less than 80% or stable disease in the neck lymph nodes (especially if N2 or N3 disease) after induction CT were referred to surgery for neck dissection, if the surgeons were in agreement, before the administration of CRT." Patients with no response or progression of disease were taken off study.''
+''Restaging of disease takes place 2 weeks after finishing cycle 3. Patients who had "at least 50% regression of their primary tumor volume and who recovered larynx mobility" were treated with Chemoradiotherapy. Patients who did not have at least 50% regression had salvage total laryngectomy.''
 ====Chemoradiotherapy====
 *[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV once per day on days 1, 22, 43
-*Concurrent radiation therapy to primary tumor, 2 Gy fractions x 35 fractions (total dose: 70 Gy), given 5 times per week over 7 weeks. Nodal areas not involved by tumor received 50 Gy.
+*Concurrent radiation therapy, 2 Gy fractions x 35 fractions (total dose: 70 Gy), given once per day 5 times per week over 7 weeks
-===References===
+===Regimen #3 {{#subobject:425bf|Variant=1}}===
-# Hitt R, López-Pousa A, Martínez-Trufero J, Escrig V, Carles J, Rizo A, Isla D, Vega ME, Martí JL, Lobo F, Pastor P, Valentí V, Belón J, Sánchez MA, Chaib C, Pallarés C, Antón A, Cervantes A, Paz-Ares L, Cortés-Funes H. 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 Dec 1;23(34):8636-45. Epub 2005 Nov 7. [http://jco.ascopubs.org/content/23/34/8636.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/16275937 PubMed]
+{| border="1" style="text-align:center;" !align="left"
+|'''Study'''
-==Cisplatin, Fluorouracil, Paclitaxel (PCF, PPF) -> Paclitaxel & concurrent RT {{#subobject:efeb5|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
-PCF: '''<u>P</u>'''aclitaxel, '''<u>C</u>'''isplatin, '''<u>F</u>'''luorouracil
-<br>PPF: '''<u>P</u>'''aclitaxel, '''<u>P</u>'''latinol, '''<u>F</u>'''luorouracil
-===Regimen {{#subobject:d5e568|Variant=1}}===
-{| border="1" style="text-align:center;" !align="left"
-|'''Study'''
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |-
-|[http://annonc.oxfordjournals.org/content/13/10/1665.long Hitt et al. 2002]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2967367/ Adelstein et al. 2010 (SWOG S0216)]
 |style="background-color:#EEEE00"|Phase II
 |-
@@ Line 993: / Line 1,077: @@
 ====Chemotherapy====
-*[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV over 3 hours once on day 1
+*[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV once on day 1
-*[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV over 1 hour once on day 2
+*[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV once on day 1
-*[[Fluorouracil (5-FU)]] 500 mg/m<sup>2</sup>/day IV continuous infusion over 5 days on days 2 to 6 (total dose per cycle: 2500 mg/m<sup>2</sup>)
+*[[Fluorouracil (5-FU)]] 1000 mg/m<sup>2</sup>/day IV continuous infusion over 4 days on days 1 to 4 (total dose per cycle: 4000 mg/m<sup>2</sup>)
 ====Supportive medications====
-*[[Dexamethasone (Decadron)]] 20 mg IV once 30 minutes prior to [[Paclitaxel (Taxol)]]
+*Ciprofloxacin (Cipro) prophylaxis for 10 days (dose/route/precise schedule not specified)
-*[[Dexamethasone (Decadron)]] 8 mg PO BID on days 2 & 3
+*"Standard anti-emetics, hydration and diuresis"
-*Ondansetron (Zofran) 8 mg IV/PO Q8H or Q12H on days 1 to 5
-*Diphenhydramine (Benadryl) 50 mg IV once 30 minutes prior to [[Paclitaxel (Taxol)]]
-*Cimetidine (Tagamet) 300 mg (or ranitidine, unspecified dosage, per Hitt et al. 2005) IV once 30 minutes prior to [[Paclitaxel (Taxol)]]
-*Mannitol and IV hydration with [[Cisplatin (Platinol)]]
-'''3-week cycle for 3 cycles'''
+'''21-day cycle for 2 cycles'''
-''Patients undergo ENT evaluation and CT imaging of the primary tumor and neck during week 3 or 4 of cycle 3. Patients who did not have at least a partial response were recommended for surgery. Patients with bulky nodal disease prior to therapy "and/or suboptimal response to induction chemotherapy" were recommended for neck dissection before radiation therapy. Surgery was performed 4 weeks after cycle 3 day 1. Patients with complete response (CR) or partial response proceeded to chemoradiotherapy; radiation therapy alone was used "if concomitant treatment was not feasible."''
+''Restaging of disease takes place 3 weeks after finishing cycle 2. Patients with stable or tumors which responded to therapy proceed to concurrent Chemoradiotherapy therapy. Patients with progressive disease are considered--if possible--for surgical resection and post-operative radiation. Patients who could not undergo surgery also received concurrent Chemoradiotherapy therapy.''
 ====Chemoradiotherapy====
-''Chemoradiotherapy starts 4 to 6 weeks after cycle 3 day 1 or as soon as patients recover from surgery (if any).''
+*[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV once per day on days 1 & 22
-*[[Paclitaxel (Taxol)]] 25 mg/m<sup>2</sup> IV over 1 hour once per week during radiation therapy, starting on day 1
+*Concurrent radiation therapy, 1.8 Gy fractions x 30 fractions, given 5 times per week (total dose: 54 Gy)
-*Concurrent radiation therapy to primary unresected tumors, 1.8 to 2 Gy fractions (total dose: 65 to 70 Gy). Post-operative areas received 60 Gy. Nodal areas not involved by tumor received at least 45 Gy.
+**The last 12 treatments involved a boost volume, 1.5 Gy fractions x 12 fractions (dose to boost volume: 18 Gy)
 ====Supportive medications====
-*"Usual pre-medication was given before each paclitaxel infusion" (presumably the same ones used during induction chemotherapy).
+*"Standard hydration and anti-emetic therapy"
-===References===
+'''6-week course;''' "Surgical resection was considered after concomitant chemoradiotherapy for those patients with histologically confirmed residual or recurrent disease at the primary site."
-# Hitt R, Paz-Ares L, Brandáriz A, Castellano D, Peña C, Millán JM, Calvo F, Ortiz de Urbina D, López E, Alvarez-Vicent JJ, Cortés-Funes H. Induction chemotherapy with paclitaxel, cisplatin and 5-fluorouracil for squamous cell carcinoma of the head and neck: long-term results of a phase II trial. Ann Oncol. 2002 Oct;13(10):1665-73. [http://annonc.oxfordjournals.org/content/13/10/1665.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/12377658 PubMed]
-==Cisplatin, Paclitaxel, concurrent RT {{#subobject:d482cc|Regimen=1}}==
+===Regimen #4 {{#subobject:2d63b4|Variant=1}}===
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
-===Regimen {{#subobject:6f799d|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
-|'''Comparator'''
 |-
-|[http://jco.ascopubs.org/content/22/14/2856.long Garden et al. 2004 (RTOG 97-03)]
+|[http://link.springer.com/article/10.1007%2Fs00280-009-1152-0 Bae et al. 2010]
-|style="background-color:#00CD00"|Randomized Phase II
+|style="background-color:#EEEE00"|Phase II
-|[[#Cisplatin.2C_Fluorouracil_.28PF.29.2C_concurrent_RT|Cisplatin, 5-FU, RT]]<br> [[#Fluorouracil.2C_Hydroxyurea.2C_concurrent_RT|5-FU, Hydroxyurea, RT]]
 |-
 |}
-====Chemoradiotherapy====
-*[[Cisplatin (Platinol)]] 20 mg/m<sup>2</sup> IV once each Tuesday on weeks 1 to 7, given prior to radiation
-*[[Paclitaxel (Taxol)]] 30 mg/m<sup>2</sup> IV once each Monday on weeks 1 to 7, given prior to radiation
-*Concurrent radiation therapy, 2 Gy fractions x 35 fractions (total dose: 70 Gy), given 5 times per week over 7 weeks
-'''7-week course of therapy'''
+''This study only involved patients with locoregionally advanced nasopharyngeal cancer.''
+====Chemotherapy====
+*[[Docetaxel (Taxotere)]] 70 mg/m<sup>2</sup> in 300 mL normal saline IV over 1 hour once on day 1, '''given first'''
+*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV over 3 hours once on day 1, '''given second'''
+*[[Fluorouracil (5-FU)]] 1000 mg/m<sup>2</sup>/day IV continuous infusion over 4 days on days 1 to 4, '''started after completion of cisplatin''' (total dose per cycle: 4000 mg/m<sup>2</sup>)
+====Supportive medications====
+*[[Dexamethasone (Decadron)]] 20 mg IV once 30 minutes prior to [[Docetaxel (Taxotere)]]
+*[[Ranitidine (Zantac)]] 50 mg IV once 30 minutes prior to [[Docetaxel (Taxotere)]]
+*[[Chlorpheniramine (Chlor-Trimeton)]] 5 mg IV once 30 minutes prior to [[Docetaxel (Taxotere)]]
+*Posthydration after [[Cisplatin (Platinol)]] with normal saline (volume/rate not specified)
+*[[Ondansetron (Zofran)]] 8 mg IV "was routinely given"
+*[[Levofloxacin (Levaquin)]] 500 mg PO once per day on days 5 to 10 as prophylaxis
+*Prophylactic [[Filgrastim (Neupogen)|G-CSF]] per physician's discretion
+'''21-day cycle for 3 cycles; then proceed to chemoradiotherapy:'''
+====Chemoradiotherapy====
+*[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV once per day on days 1 & 22
+*Concurrent radiation therapy, 1.8 to 2 Gy fractions (total dose: 68.4 Gy), given 5 times per week
 ===References===
-# Garden AS, Harris J, Vokes EE, Forastiere AA, Ridge JA, Jones C, Horwitz EM, Glisson BS, Nabell L, Cooper JS, Demas W, Gore E. Preliminary results of Radiation Therapy Oncology Group 97-03: a randomized phase ii trial of concurrent radiation and chemotherapy for advanced squamous cell carcinomas of the head and neck. J Clin Oncol. 2004 Jul 15;22(14):2856-64. [http://jco.ascopubs.org/content/22/14/2856.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/15254053 PubMed]
+# Adelstein DJ, Moon J, Hanna E, Giri PG, Mills GM, Wolf GT, Urba SG. 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 Feb;32(2):221-8. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2967367/ link to PMC article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19557750 PubMed]
+# Bae WK, Hwang JE, Shim HJ, Cho SH, Lee JK, Lim SC, Chung WK, Chung IJ. Phase II study of docetaxel, cisplatin, and 5-FU induction chemotherapy followed by chemoradiotherapy in locoregionally advanced nasopharyngeal cancer. Cancer Chemother Pharmacol. 2010 Feb;65(3):589-95. [http://link.springer.com/article/10.1007%2Fs00280-009-1152-0 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19830427 PubMed]
+<!-- Presented as oral presentations at the 45th Annual Meeting of the American Society of Clinical Oncology (ASCO), Orlando, FL, May 29-June 2, 2009, and at the 47th Annual Meeting of ASCO, Chicago, IL, June 3-7, 2011. -->
+# Lefebvre JL, Pointreau Y, Rolland F, Alfonsi M, Baudoux A, Sire C, de Raucourt D, Malard O, Degardin M, Tuchais C, Blot E, Rives M, Reyt E, Tourani JM, Geoffrois L, Peyrade F, Guichard F, Chevalier D, Babin E, Lang P, Janot F, Calais G, Garaud P, Bardet E. Induction chemotherapy followed by either chemoradiotherapy or bioradiotherapy for larynx preservation: the TREMPLIN randomized phase II study. J Clin Oncol. 2013 Mar 1;31(7):853-9. Epub 2013 Jan 22. [http://jco.ascopubs.org/content/31/7/853.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23341517 PubMed]
+# Sun Y, Li WF, Chen NY, Zhang N, Hu GQ, Xie FY, Sun Y, Chen XZ, Li JG, Zhu XD, Hu CS, Xu XY, Chen YY, Hu WH, Guo L, Mo HY, Chen L, Mao YP, Sun R, Ai P, Liang SB, Long GX, Zheng BM, Feng XL, Gong XC, Li L, Shen CY, Xu JY, Guo Y, Chen YM, Zhang F, Lin L, Tang LL, Liu MZ, Ma J. Induction chemotherapy plus concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: a phase 3, multicentre, randomised controlled  trial. Lancet Oncol. 2016 Sep 26. [Epub ahead of print] [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(16)30410-7/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/27686945 PubMed]
-==Fluorouracil, Hydroxyurea, concurrent RT {{#subobject:3f664e|Regimen=1}}==
+==TPF -> RT {{#subobject:99e8bb|Regimen=1}}==
 {| class="wikitable" style="float:right; margin-left: 5px;"
 |-
 |[[#top|back to top]]
 |}
+DCF: '''<u>D</u>'''ocetaxel, '''<u>C</u>'''isplatin, '''<u>F</u>'''luorouracil
-===Regimen {{#subobject:892cec|Variant=1}}===
+<br>TPF: '''<u>T</u>'''axotere (Docetaxel), '''<u>P</u>'''latinol (Cisplatin), '''<u>F</u>'''luorouracil
+<br>RT: '''<u>R</u>'''adiation '''<u>T</u>'''herapy
+===Regimen #1 {{#subobject:6c7d09|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
-|[http://jco.ascopubs.org/content/22/14/2856.long Garden et al. 2004 (RTOG 97-03)]
+|[http://www.nejm.org/doi/full/10.1056/NEJMoa071028 Vermorken et al. 2007 (EORTC 24971/TAX 323)]
-|style="background-color:#00CD00"|Randomized Phase II
+|style="background-color:#00CD00"|Phase III
-|[[#Cisplatin.2C_Fluorouracil_.28PF.29.2C_concurrent_RT|Cisplatin, 5-FU, RT]]<br> [[#Cisplatin.2C_Paclitaxel.2C_concurrent_RT|Cisplatin, Paclitaxel, RT]]
+|[[#CF_-.3E_RT|CF -> RT]]
+|style="background-color:#00CD00"|Seems to have superior OS
 |-
 |}
-====Chemoradiotherapy====
+====Chemotherapy====
-*[[Fluorouracil (5-FU)]] 800 mg/m<sup>2</sup>/day IV continuous infusion given 5 days per week on weeks 1, 3, 5, 7, 9, 11, 13 (total dose per week: 4000 mg/m<sup>2</sup>)
+*[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV over 1 hour once on day 1, '''given first before cisplatin'''
-**''Note: Garden et al. 2004 was not clear about the exact schedule nor duration of the continuous infusion, such as whether each continuous infusion was over 24 hours or not''
+*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV over 1 hour once on day 1, '''given second after docetaxel'''
-*[[Hydroxyurea (Hydrea)]] 1000 mg PO every 12 hours x 11 doses per week on weeks 1, 3, 5, 7, 9, 11, 13 (total dose per week: 11,000 mg)
+*[[Fluorouracil (5-FU)]] 750 mg/m<sup>2</sup>/day IV continuous infusion over 5 days on days 1 to 5 (total dose per cycle: 3750 mg/m<sup>2</sup>)
-**''Note: Garden et al. 2004 did not clearly specify when the doses of hydroxyurea were to be taken in relation to radiation treatments''
-*Concurrent radiation therapy, 2 Gy fractions x 35 fractions (total dose: 70 Gy), given 5 times per week on weeks 1, 3, 5, 7, 9, 11, 13
-'''13-week course of therapy'''
+====Supportive medications====
+*[[Dexamethasone (Decadron)]] 8 mg PO for 6 doses (exact schedule not specified) starting the night before [[Docetaxel (Taxotere)]]
+*[[Ciprofloxacin (Cipro)]] 500 mg PO BID "or an alternative agent" on days 5 to 15 as prophylaxis
+*"Adequate [[Antiemesis|antiemetic]] medications during chemotherapy"
+*Prophylactic [[Filgrastim (Neupogen)|granulocyte colony-stimulating factor]] only allowed for patients who had "febrile neutropenia or infection, a delay in recovery of the absolute neutrophil count at day 28, or grade 4 neutropenia persisting for 7 days or more."
-===References===
+'''21-day cycle for 4 cycles'''
-# Garden AS, Harris J, Vokes EE, Forastiere AA, Ridge JA, Jones C, Horwitz EM, Glisson BS, Nabell L, Cooper JS, Demas W, Gore E. Preliminary results of Radiation Therapy Oncology Group 97-03: a randomized phase ii trial of concurrent radiation and chemotherapy for advanced squamous cell carcinomas of the head and neck. J Clin Oncol. 2004 Jul 15;22(14):2856-64. [http://jco.ascopubs.org/content/22/14/2856.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/15254053 PubMed]
-==Radiation therapy {{#subobject:5ac377|Regimen=1}}==
+''Patients without progressive disease and who had recovery of marrow function, resolution of mucositis, and healed from any dental procedures started radiation therapy within 4 to 7 weeks of finishing chemotherapy:''
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
-===Regimen {{#subobject:ce3d2d|Variant=1}}===
+====Radiotherapy====
-{| border="1" style="text-align:center;" !align="left"
+*Radiation therapy over 7 weeks with one of the following (further details not provided):
+**Conventional fractionation, total dose 66 to 70 Gy
+**Accelerated fractionation, total dose 70 Gy
+**Hyperfractionated, total dose 74 Gy
+===Regimen #2 {{#subobject:e085d0|Variant=1}}===
+{| border="1" style="text-align:center;" !align="left"
 |'''Study'''
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
-|[http://jco.ascopubs.org/content/16/4/1310.long Al-Sarraf et al. 1998 (Intergroup 0099)]
+|[http://jnci.oxfordjournals.org/content/101/7/498.long Pointreau et al. 2009 (GORTEC)]
-|style="background-color:#00CD00"|Phase III
-|[[#Cisplatin_.26_RT_-.3E_Cisplatin_.26_Fluorouracil|Cisplatin & RT -> Cisplatin & 5-FU]]
-|-
-|[http://jco.ascopubs.org/content/21/1/92.long Adelstein et al. 2003]
-|style="background-color:#00CD00"|Phase III
-|[[#Cisplatin.2C_Fluorouracil_.28PF.29.2C_concurrent_RT|Cisplatin, 5-FU, RT]]<br> [[#Cisplatin_.26_concurrent_RT_2|Cisplatin & RT]]
-|-
-|[http://www.nejm.org/doi/full/10.1056/NEJMoa031317 Forastiere et al. 2003 (RTOG 91-11)]
-|style="background-color:#00CD00"|Phase III
-|[[#Cisplatin_.26_Fluorouracil_.28PF.29_-.3E_sequential_RT|Cisplatin & 5-FU -> RT]]<br> [[#Cisplatin_.26_concurrent_RT_2|Cisplatin & RT]]
-|-
-|[http://jco.ascopubs.org/content/22/1/69.long Denis et al. 2004 (94-01)]
 |style="background-color:#00CD00"|Phase III
-|[[#Carboplatin.2C_Fluorouracil.2C_concurrent_RT|Carboplatin, 5-FU, RT]]
+|[[#CF_-.3E_RT|CF -> RT]]
-|-
+|style="background-color:#00CD00"|Superior ORR
-|[http://jnci.oxfordjournals.org/content/97/7/536.long Chan et al. 2005]
-|style="background-color:#00CD00"|Phase III
-|[[#Cisplatin_.26_concurrent_RT_2|Cisplatin & RT]]
-|-
-|[http://www.nejm.org/doi/full/10.1056/NEJMoa053422 Bonner et al. 2006 (IMCL-9815)]
-|style="background-color:#00CD00"|Phase III
-|[[#Cetuximab_.26_concurrent_RT|Cetuximab & RT]]
-|-
-|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(11)70346-1/abstract Bourhis et al. 2012 (GORTEC 99-02)]
-|style="background-color:#00CD00"|Phase III
-|[[#Carboplatin.2C_Fluorouracil.2C_concurrent_RT|Carboplatin, 5-FU, RT]]<br> Carboplatin, 5-FU, accelerated concurrent RT
 |-
 |}
+====Chemotherapy====
-''Used as a comparator arm; included for reference purposes only.''
+*[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV over 1 hour once on day 1
+*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV over 1 hour once on day 1
+*[[Fluorouracil (5-FU)]] 750 mg/m<sup>2</sup>/day IV continuous infusion over 5 days on days 1 to 5 (total dose per cycle: 3750 mg/m<sup>2</sup>)
+====Supportive medications====
+*Normal saline (use of mannitol, KCl, and magnesium sulfate per institutional protocol) 1000 mL IV given twice, before and after [[Cisplatin (Platinol)]]
+*[[Dexamethasone (Decadron)]] 8 mg PO once per day the day before, the day of, and day after [[Docetaxel (Taxotere)]]
+*[[Ciprofloxacin (Cipro)]] 1000 mg PO (frequency not specified) on days 5 to 15
+*Prophylactic [[Filgrastim (Neupogen)|granulocyte colony-stimulating factor]] not used
+'''21-day cycle for 3 cycles'''
+''Patients who responded to induction chemotherapy proceeded to radiation therapy within 3 to 7 weeks of finishing chemotherapy. Patients who did not respond to induction chemotherapy proceeded to surgery and postoperative radiotherapy (see Pointreau et al. 2009 for details).''
+====Radiotherapy====
+*Radiation therapy to the primary tumor and involved lymph nodes, 2 Gy fractions x 35 fractions (total dose: 70 Gy), given 5 times per week over 7 weeks. Prophylactic radiation to the volume at risk for microscopic disease, 2 Gy fractions x 25 to 27 fractions (total dose: 50 to 54 Gy), given 5 times per week.
+*"Chemotherapy (cisplatin, carboplatin, and 5-fluorouracil or a combination of two drugs) during radiotherapy was allowed for all patients who were treated at the same institute, according to its practice." No further details available.
 ===References===
-# Al-Sarraf M, LeBlanc M, Giri PG, Fu KK, Cooper J, Vuong T, Forastiere AA, Adams G, Sakr WA, Schuller DE, Ensley JF. Chemoradiotherapy versus radiotherapy in patients with advanced nasopharyngeal cancer: phase III randomized Intergroup study 0099. J Clin Oncol. 1998 Apr;16(4):1310-7. [http://jco.ascopubs.org/content/16/4/1310.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/9552031 PubMed]
+# Vermorken JB, Remenar E, van Herpen C, Gorlia T, Mesia R, Degardin M, Stewart JS, Jelic S, Betka J, Preiss JH, van den Weyngaert D, Awada A, Cupissol D, Kienzer HR, Rey A, Desaunois I, Bernier J, Lefebvre JL; EORTC 24971/TAX 323 Study Group. Cisplatin, fluorouracil, and docetaxel in unresectable head and neck cancer. N Engl J Med. 2007 Oct 25;357(17):1695-704. [http://www.nejm.org/doi/full/10.1056/NEJMoa071028 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/17960012 PubMed]
-# Adelstein DJ, Li Y, Adams GL, Wagner H Jr, Kish JA, Ensley JF, Schuller DE, Forastiere AA. 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 Jan 1;21(1):92-8. [http://jco.ascopubs.org/content/21/1/92.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/12506176 PubMed]
+## '''QoL Analysis:''' van Herpen CM, Mauer ME, Mesia R, Degardin M, Jelic S, Coens C, Betka J, Bernier J, Remenar E, Stewart JS, Preiss JH, van den Weyngaert D, Bottomley A, Vermorken JB; EORTC Head and Neck Group. Short-term health-related quality of life and symptom control with docetaxel, cisplatin, 5-fluorouracil and cisplatin (TPF), 5-fluorouracil (PF) for induction in unresectable locoregionally advanced head and neck cancer patients (EORTC 24971/TAX 323). Br J Cancer. 2010 Oct 12;103(8):1173-81. Epub 2010 Sep 14. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2967049/ link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/20842129 PubMed]
-# Forastiere AA, Goepfert H, Maor M, Pajak TF, Weber R, Morrison W, Glisson B, Trotti A, Ridge JA, Chao C, Peters G, Lee DJ, Leaf A, Ensley J, Cooper J. Concurrent chemotherapy and radiotherapy for organ preservation in advanced laryngeal cancer. N Engl J Med. 2003 Nov 27;349(22):2091-8. [http://www.nejm.org/doi/full/10.1056/NEJMoa031317 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/14645636 PubMed]
+# Pointreau Y, Garaud P, Chapet S, Sire C, Tuchais C, Tortochaux J, Faivre S, Guerrif S, Alfonsi M, Calais G. Randomized trial of induction chemotherapy with cisplatin and 5-fluorouracil with or without docetaxel for larynx preservation. J Natl Cancer Inst. 2009 Apr 1;101(7):498-506. Epub 2009 Mar 24. [http://jnci.oxfordjournals.org/content/101/7/498.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19318632 PubMed] content property of [http://hemonc.org HemOnc.org]
-## '''Update:''' Forastiere AA, Zhang Q, Weber RS, Maor MH, Goepfert H, Pajak TF, Morrison W, Glisson B, Trotti A, Ridge JA, Thorstad W, Wagner H, Ensley JF, Cooper JS. Long-term results of RTOG 91-11: a comparison of three nonsurgical treatment strategies to preserve the larynx in patients with locally advanced larynx cancer. J Clin Oncol. 2013 Mar 1;31(7):845-52. Epub 2012 Nov 26. [http://jco.ascopubs.org/content/31/7/845.long link to original article] '''contains partial protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/23182993 PubMed]
-# Denis F, Garaud P, Bardet E, Alfonsi M, Sire C, Germain T, Bergerot P, Rhein B, Tortochaux J, Calais G. Final results of the 94-01 French Head and Neck Oncology and Radiotherapy Group randomized trial comparing radiotherapy alone with concomitant radiochemotherapy in advanced-stage oropharynx carcinoma. J Clin Oncol. 2004 Jan 1;22(1):69-76. Epub 2003 Dec 2. [http://jco.ascopubs.org/content/22/1/69.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/14657228 PubMed]
-# Chan AT, Leung SF, Ngan RK, Teo PM, Lau WH, Kwan WH, Hui EP, Yiu HY, Yeo W, Cheung FY, Yu KH, Chiu KW, Chan DT, Mok TS, Yau S, Yuen KT, Mo FK, Lai MM, Ma BB, Kam MK, Leung TW, Johnson PJ, Choi PH, Zee BC. Overall survival after concurrent cisplatin-radiotherapy compared with radiotherapy alone in locoregionally advanced nasopharyngeal carcinoma. J Natl Cancer Inst. 2005 Apr 6;97(7):536-9. [http://jnci.oxfordjournals.org/content/97/7/536.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/15812080 PubMed]
-# Bonner JA, Harari PM, Giralt J, Azarnia N, Shin DM, Cohen RB, Jones CU, Sur R, Raben D, Jassem J, Ove R, Kies MS, Baselga J, Youssoufian H, Amellal N, Rowinsky EK, Ang KK. Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med. 2006 Feb 9;354(6):567-78. [http://www.nejm.org/doi/full/10.1056/NEJMoa053422 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/16467544 PubMed]
-## '''Update:''' Bonner JA, Harari PM, Giralt J, Cohen RB, Jones CU, Sur RK, Raben D, Baselga J, Spencer SA, Zhu J, Youssoufian H, Rowinsky EK, Ang KK. Radiotherapy plus cetuximab for locoregionally advanced head and neck cancer: 5-year survival data from a phase 3 randomised trial, and relation between cetuximab-induced rash and survival. Lancet Oncol. 2010 Jan;11(1):21-8. Epub 2009 Nov 10. [http://www.sciencedirect.com/science/article/pii/S1470204509703110 link to original article] '''contains partial protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/19897418 PubMed]
-## '''QoL Analysis:''' Curran D, Giralt J, Harari PM, Ang KK, Cohen RB, Kies MS, Jassem J, Baselga J, Rowinsky EK, Amellal N, Comte S, Bonner JA. Quality of life in head and neck cancer patients after treatment with high-dose radiotherapy alone or in combination with cetuximab. J Clin Oncol. 2007 Jun 1;25(16):2191-7. [http://jco.ascopubs.org/content/25/16/2191.long link to original article] '''contains partial protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/17538164 PubMed]
-## '''Retrospective subgroup analysis:''' Rosenthal DI, Harari PM, Giralt J, Bell D, Raben D, Liu J, Schulten J, Ang KK, Bonner JA. Association of Human Papillomavirus and p16 Status With Outcomes in the IMCL-9815 Phase III Registration Trial for Patients With Locoregionally Advanced Oropharyngeal Squamous Cell Carcinoma of the Head and Neck Treated With Radiotherapy With or Without Cetuximab. J Clin Oncol. 2016 Apr 20;34(12):1300-8. Epub 2015 Dec 28. [http://jco.ascopubs.org/content/34/12/1300.full link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/26712222 PubMed]
-# Bourhis J, Sire C, Graff P, Grégoire V, Maingon P, Calais G, Gery B, Martin L, Alfonsi M, Desprez P, Pignon T, Bardet E, Rives M, Geoffrois L, Daly-Schveitzer N, Sen S, Tuchais C, Dupuis O, Guerif S, Lapeyre M, Favrel V, Hamoir M, Lusinchi A, Temam S, Pinna A, Tao YG, Blanchard P, Aupérin A. Concomitant chemoradiotherapy versus acceleration of radiotherapy with or without concomitant chemotherapy in locally advanced head and neck carcinoma (GORTEC 99-02): an open-label phase 3 randomised trial. Lancet Oncol. 2012 Feb;13(2):145-53. Epub 2012 Jan 18. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(11)70346-1/abstract link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22261362 PubMed]
 =Recurrent or metastatic disease=
@@ Line 1,181: / Line 1,265: @@
 ===References===
-# Samlowski WE, Moon J, Kuebler JP, Nichols CR, Gandara DR, Ozer H, Williamson SK, Atkins JN, Schuller DE, Ensley JF. 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 Apr-May;25(3):182-8. [http://informahealthcare.com/doi/abs/10.1080/07357900701209061 link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/17530488 PubMed]
+# Samlowski WE, Moon J, Kuebler JP, Nichols CR, Gandara DR, Ozer H, Williamson SK, Atkins JN, Schuller DE, Ensley JF. 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 Apr-May;25(3):182-8. [http://informahealthcare.com/doi/abs/10.1080/07357900701209061 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/17530488 PubMed]
 ==Carboplatin & Fluorouracil {{#subobject:125a7d|Regimen=1}}==
@@ Line 1,193: / Line 1,277: @@
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
-|[http://jco.ascopubs.org/content/10/8/1245.long Forastiere et al. 1992]
+|rowspan=2|[http://jco.ascopubs.org/content/10/8/1245.long Forastiere et al. 1992]
-|style="background-color:#00CD00"|Phase III
+|rowspan=2 style="background-color:#00CD00"|Phase III
-|[[Head_and_neck_cancer#Cisplatin_.26_Fluorouracil_.28CF.29|Cisplatin & Fluorouracil]]<br> [[Head_and_neck_cancer#Methotrexate_.28MTX.29|MTX]]
+|[[#CF_2|CF]]
+|style="background-color:#d3d3d3"|Not reported
+|-
+|[[Head_and_neck_cancer#Methotrexate_.28MTX.29|MTX]]
+|style="background-color:#00CD00"|Seems to have superior ORR
 |-
 |[http://www.nejm.org/doi/full/10.1056/NEJMoa0802656 Vermorken et al. 2008]
 |style="background-color:#00CD00"|Phase III
 |[[Head_and_neck_cancer#Carboplatin.2C_Fluorouracil.2C_Cetuximab|Carboplatin, Fluorouracil, Cetuximab]]
+|style="background-color:#ff0000"|Seems to have inferior OS
 |-
 |}
@@ Line 1,213: / Line 1,303: @@
 ===References===
-# Forastiere AA, Metch B, Schuller DE, Ensley JF, Hutchins LF, Triozzi P, Kish JA, McClure S, VonFeldt E, Williamson SK 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 Aug;10(8):1245-51. [http://jco.ascopubs.org/content/10/8/1245.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/1634913 PubMed]
+# Forastiere AA, Metch B, Schuller DE, Ensley JF, Hutchins LF, Triozzi P, Kish JA, McClure S, VonFeldt E, Williamson SK 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 Aug;10(8):1245-51. [http://jco.ascopubs.org/content/10/8/1245.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/1634913 PubMed]
-# Vermorken JB, Mesia R, Rivera F, Remenar E, Kawecki A, Rottey S, Erfan J, Zabolotnyy D, Kienzer HR, Cupissol D, Peyrade F, Benasso M, Vynnychenko I, De Raucourt D, Bokemeyer C, Schueler A, Amellal N, Hitt R. Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med. 2008 Sep 11;359(11):1116-27. [http://www.nejm.org/doi/full/10.1056/NEJMoa0802656 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/18784101 PubMed]
+# Vermorken JB, Mesia R, Rivera F, Remenar E, Kawecki A, Rottey S, Erfan J, Zabolotnyy D, Kienzer HR, Cupissol D, Peyrade F, Benasso M, Vynnychenko I, De Raucourt D, Bokemeyer C, Schueler A, Amellal N, Hitt R. Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med. 2008 Sep 11;359(11):1116-27. [http://www.nejm.org/doi/full/10.1056/NEJMoa0802656 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18784101 PubMed]
 ==Carboplatin, Fluorouracil, Cetuximab {{#subobject:286b8b|Regimen=1}}==
@@ Line 1,227: / Line 1,317: @@
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
 |[http://www.nejm.org/doi/full/10.1056/NEJMoa0802656 Vermorken et al. 2008]
 |style="background-color:#00CD00"|Phase III
 |[[Head_and_neck_cancer#Carboplatin_.26_Fluorouracil|Carboplatin & Fluorouracil]]
+|style="background-color:#00CD00"|Seems to have superior OS
 |-
 |}
@@ Line 1,243: / Line 1,335: @@
 ===References===
-# Vermorken JB, Mesia R, Rivera F, Remenar E, Kawecki A, Rottey S, Erfan J, Zabolotnyy D, Kienzer HR, Cupissol D, Peyrade F, Benasso M, Vynnychenko I, De Raucourt D, Bokemeyer C, Schueler A, Amellal N, Hitt R. Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med. 2008 Sep 11;359(11):1116-27. [http://www.nejm.org/doi/full/10.1056/NEJMoa0802656 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/18784101 PubMed]
+# Vermorken JB, Mesia R, Rivera F, Remenar E, Kawecki A, Rottey S, Erfan J, Zabolotnyy D, Kienzer HR, Cupissol D, Peyrade F, Benasso M, Vynnychenko I, De Raucourt D, Bokemeyer C, Schueler A, Amellal N, Hitt R. Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med. 2008 Sep 11;359(11):1116-27. [http://www.nejm.org/doi/full/10.1056/NEJMoa0802656 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18784101 PubMed]
 ==Cetuximab (Erbitux) {{#subobject:4b973b|Regimen=1}}==
@@ Line 1,264: / Line 1,356: @@
 ===References===
-# Vermorken JB, Trigo J, Hitt R, Koralewski P, Diaz-Rubio E, Rolland F, Knecht R, Amellal N, Schueler A, Baselga J. 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 Jun 1;25(16):2171-7. [http://jco.ascopubs.org/content/25/16/2171.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/17538161 PubMed]
+# Vermorken JB, Trigo J, Hitt R, Koralewski P, Diaz-Rubio E, Rolland F, Knecht R, Amellal N, Schueler A, Baselga J. 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 Jun 1;25(16):2171-7. [http://jco.ascopubs.org/content/25/16/2171.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/17538161 PubMed]
-==Cisplatin {{#subobject:33b395|Regimen=1}}==
+==CF {{#subobject:b42ea5|Regimen=1}}==
 {| class="wikitable" style="float:right; margin-left: 5px;"
 |-
 |[[#top|back to top]]
 |}
+CF: '''<u>C</u>'''isplatin and '''<u>F</u>'''luorouracil
-===Regimen {{#subobject:f5e770|Variant=1}}===
+===Regimen #1 {{#subobject:afff01|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
-|[http://jco.ascopubs.org/content/23/34/8646.long Burtness et al. 2005]
+|[http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(16)31388-5/fulltext Zhang et al. 2016]
-|style="background-color:#00CD00"|Phase III
+|style="background-color:#00cd00"|Phase III
-|[[Head_and_neck_cancer#Cisplatin_.26_Cetuximab|Cisplatin & Cetuximab]]
+|[[#Cisplatin_.26_Gemcitabine|Cisplatin & Gemcitabine]]
+|style="background-color:#ff0000"|Inferior PFS
 |-
 |}
+''Note: this regimen was intended for recurrent or metastatic nasopharyngeal carcinoma.''
 ====Chemotherapy====
-*[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV once on day 1
+*[[Cisplatin (Platinol)]] 80 mg/m<sup>2</sup> IV once on day 1
+*[[Fluorouracil (5-FU)]] 1000 mg/m<sup>2</sup>/day IV continuous infusion on days 1 to 4 (total dose per cycle: 4000 mg/m<sup>2</sup>)
-'''28-day cycles'''
+'''21-day cycle for up to 6 cycles'''
-''Per physician discretion, patients with complete response (CR) could have treatment discontinued 2 cycles past the point at which CR was attained. Patients with partial response (PR) continued on treatment until there was evidence of CR or progression disease. Patients with stable disease (SD) could discontinue treatment after 6 cycles. Patients with progressive disease discontinued therapy.''
+===Regimen #2 {{#subobject:8e0178|Variant=1}}===
+{| border="1" style="text-align:center;" !align="left"
-===References===
+|'''Study'''
-# Burtness B, Goldwasser MA, Flood W, Mattar B, Forastiere AA; Eastern Cooperative Oncology Group. 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 Dec 1;23(34):8646-54. [http://jco.ascopubs.org/content/23/34/8646.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/16314626 PubMed]
+|[[Levels_of_Evidence#Evidence|'''Evidence''']]
+|'''Comparator'''
-==Cisplatin & Cetuximab {{#subobject:58744c|Regimen=1}}==
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
-{| class="wikitable" style="float:right; margin-left: 5px;"
+|-
+|rowspan=2|[http://jco.ascopubs.org/content/10/8/1245.long Forastiere et al. 1992]
+|rowspan=2 style="background-color:#00cd00"|Phase III
+|[[Head_and_neck_cancer#Carboplatin_.26_Fluorouracil|Carboplatin & Fluorouracil]]
+|style="background-color:#d3d3d3"|Not reported
 |-
-|[[#top|back to top]]
+|[[Head_and_neck_cancer#Methotrexate_.28MTX.29|MTX]]
-|}
+|style="background-color:#00cd00"|Superior ORR
-===Regimen {{#subobject:c40d1f|Variant=1}}===
-{| border="1" style="text-align:center;" !align="left"
-|'''Study'''
-|[[Levels_of_Evidence#Evidence|'''Evidence''']]
-|'''Comparator'''
 |-
-|[http://jco.ascopubs.org/content/23/34/8646.long Burtness et al. 2005]
+|[http://jco.ascopubs.org/content/23/15/3562.long Gibson et al. 2005 (ECOG E1395)]
-|style="background-color:#00CD00"|Phase III
+|style="background-color:#00cd00"|Phase III
-|[[Head_and_neck_cancer#Cisplatin|Cisplatin]]
+|[[#CP|CP]]
+|style="background-color:#eeee00"|Seems not superior
 |-
-|}
+|[http://www.nejm.org/doi/full/10.1056/NEJMoa0802656 Vermorken et al. 2008]
-====Chemotherapy====
+|style="background-color:#00cd00"|Phase III
-*[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV once on day 1
+|[[Head_and_neck_cancer#Cisplatin.2C_Fluorouracil.2C_Cetuximab|Cisplatin, Fluorouracil, Cetuximab]]
-*[[Cetuximab (Erbitux)]] as follows:
+|style="background-color:#ff0000"|Seems to have inferior OS
-**Cycle 1: 200 mg/m<sup>2</sup> IV over 120 minutes once on day 1, then 125 mg/m<sup>2</sup> IV over 60 minutes once per day on days 8, 15, 22
+|-
-**Subsequent cycles: 125 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1, 8, 15, 22
+|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70181-5/fulltext Vermorken et al. 2013 (SPECTRUM)]
+|style="background-color:#00cd00"|Phase III
+|[[#Cisplatin.2C_Fluorouracil.2C_Panitumumab|Cisplatin, Fluorouracil, Panitumumab]]
+|style="background-color:#ff0000"|Inferior PFS
+|-
+|}
+====Chemotherapy====
+*[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV once on day 1
+**'''ECOG E1395:''' [[Carboplatin (Paraplatin)]] AUC 6 IV once on day 1 could be substituted in patients who developed at least grade 2 neuropathy or renal impairment (creatinine clearance <50 mL/min; note: later in Gibson et al. 2005, it says that carboplatin was used for patients who had '''creatinine clearance ≤50 mL/min''')
+*[[Fluorouracil (5-FU)]] 1000 mg/m<sup>2</sup>/day IV continuous infusion on days 1 to 4 (total dose per cycle: 4000 mg/m<sup>2</sup>)
+====Supportive medications====
+*Details vary per reference
+*Pretreatment and posttreatment hydration and mannitol diuresis with [[Cisplatin (Platinol)]]
+*"Standard antiemetic regimens"
-'''28-day cycles'''
+'''21-day cycle for up to 6 cycles (SPECTRUM) or indefinitely, see note below'''
-''Per physician discretion, patients with complete response (CR) could have treatment discontinued 2 cycles past the point at which CR was attained. Patients with partial response (PR) continued on treatment until there was evidence of CR or progression disease. Patients with stable disease (SD) could discontinue treatment after 6 cycles. Patients with progressive disease discontinued therapy.''
+''In '''ECOG E1395''', patients with complete response (CR) received at least 6 cycles or 2 cycles past the point at which CR was documented, whichever came later; patients with partial response (PR) continued on treatment until there was evidence of CR or progression disease; patients with stable disease (SD) could discontinue treatment after six cycles.''
 ===References===
-# Burtness B, Goldwasser MA, Flood W, Mattar B, Forastiere AA; Eastern Cooperative Oncology Group. 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 Dec 1;23(34):8646-54. [http://jco.ascopubs.org/content/23/34/8646.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/16314626 PubMed]
+# Forastiere AA, Metch B, Schuller DE, Ensley JF, Hutchins LF, Triozzi P, Kish JA, McClure S, VonFeldt E, Williamson SK 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 Aug;10(8):1245-51. [http://jco.ascopubs.org/content/10/8/1245.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/1634913 PubMed]
+# Gibson MK, Li Y, Murphy B, Hussain MH, DeConti RC, Ensley J, Forastiere AA; Eastern Cooperative Oncology Group. 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 May 20;23(15):3562-7. [http://jco.ascopubs.org/content/23/15/3562.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/15908667 PubMed]
-==Cisplatin & Fluorouracil (CF) {{#subobject:b42ea5|Regimen=1}}==
+# Vermorken JB, Mesia R, Rivera F, Remenar E, Kawecki A, Rottey S, Erfan J, Zabolotnyy D, Kienzer HR, Cupissol D, Peyrade F, Benasso M, Vynnychenko I, De Raucourt D, Bokemeyer C, Schueler A, Amellal N, Hitt R. Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med. 2008 Sep 11;359(11):1116-27. [http://www.nejm.org/doi/full/10.1056/NEJMoa0802656 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18784101 PubMed]
+# Vermorken JB, Stöhlmacher-Williams J, Davidenko I, Licitra L, Winquist E, Villanueva C, Foa P, Rottey S, Skladowski K, Tahara M, Pai VR, Faivre S, Blajman CR, Forastiere AA, Stein BN, Oliner KS, Pan Z, Bach BA; SPECTRUM investigators. Cisplatin and fluorouracil with or without panitumumab in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck (SPECTRUM): an open-label phase 3 randomised trial. Lancet Oncol. 2013 Jul;14(8):697-710. Epub 2013 Jun 6. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70181-5/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23746666 PubMed]
+# Zhang L, Huang Y, Hong S, Yang Y, Yu G, Jia J, Peng P, Wu X, Lin Q, Xi X, Peng J, Xu M, Chen D, Lu X, Wang R, Cao X, Chen X, Lin Z, Xiong J, Lin Q, Xie C, Li Z, Pan J, Li J, Wu S, Lian Y, Yang Q, Zhao C. Gemcitabine plus cisplatin versus fluorouracil plus cisplatin in recurrent or metastatic nasopharyngeal carcinoma:a multicentre, randomised, open-label, phase 3 trial. Lancet. 2016 Aug 23. [Epub ahead of print] [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(16)31388-5/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/27567279 PubMed]
+==Cisplatin (Platinol) {{#subobject:33b395|Regimen=1}}==
 {| class="wikitable" style="float:right; margin-left: 5px;"
 |-
 |[[#top|back to top]]
 |}
-===Regimen #1 {{#subobject:afff01|Variant=1}}===
+===Regimen {{#subobject:f5e770|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
@@ Line 1,335: / Line 1,449: @@
 |[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
-|[http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(16)31388-5/fulltext Zhang et al. 2016]
+|[http://jco.ascopubs.org/content/23/34/8646.long Burtness et al. 2005]
-|style="background-color:#00cd00"|Phase III
+|style="background-color:#00CD00"|Phase III
-|[[#Cisplatin_.26_Gemcitabine|Cisplatin & Gemcitabine]]
+|[[Head_and_neck_cancer#Cisplatin_.26_Cetuximab|Cisplatin & Cetuximab]]
-|style="background-color:#ff0000"|Inferior PFS
+|style="background-color:#eeee00"|Seems not superior
 |-
 |}
-''Note: this regimen was intended for recurrent or metastatic nasopharyngeal carcinoma.''
 ====Chemotherapy====
-*[[Cisplatin (Platinol)]] 80 mg/m<sup>2</sup> IV once on day 1
+*[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV once on day 1
-*[[Fluorouracil (5-FU)]] 1000 mg/m<sup>2</sup>/day IV continuous infusion on days 1 to 4 (total dose per cycle: 4000 mg/m<sup>2</sup>)
+'''28-day cycles'''
-'''21-day cycle for up to 6 cycles'''
+''Per physician discretion, patients with complete response (CR) could have treatment discontinued 2 cycles past the point at which CR was attained. Patients with partial response (PR) continued on treatment until there was evidence of CR or progression disease. Patients with stable disease (SD) could discontinue treatment after 6 cycles. Patients with progressive disease discontinued therapy.''
-===Regimen #2 {{#subobject:8e0178|Variant=1}}===
+===References===
-{| border="1" style="text-align:center;" !align="left"
+<!-- Presented in part at the 38th Annual Meeting of the American Society of Clinical Oncology, May 18-21, Orlando, FL, and the American Association for Cancer Research/National Cancer Institute/European Organisation for Research and Treatment of Cancer International Conference on Molecular Targets in Cancer Therapy, November 17-21, 2003, Boston, MA. -->
-|'''Study'''
+# Burtness B, Goldwasser MA, Flood W, Mattar B, Forastiere AA; Eastern Cooperative Oncology Group. 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 Dec 1;23(34):8646-54. [http://jco.ascopubs.org/content/23/34/8646.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/16314626 PubMed]
+==Cisplatin & Cetuximab {{#subobject:58744c|Regimen=1}}==
+{| class="wikitable" style="float:right; margin-left: 5px;"
+|-
+|[[#top|back to top]]
+|}
+===Regimen {{#subobject:c40d1f|Variant=1}}===
+{| border="1" style="text-align:center;" !align="left"
+|'''Study'''
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
 |[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
-|rowspan=2|[http://jco.ascopubs.org/content/10/8/1245.long Forastiere et al. 1992]
+|[http://jco.ascopubs.org/content/23/34/8646.long Burtness et al. 2005]
-|rowspan=2 style="background-color:#00cd00"|Phase III
+|style="background-color:#00CD00"|Phase III
-|[[Head_and_neck_cancer#Carboplatin_.26_Fluorouracil|Carboplatin & Fluorouracil]]
+|[[Head_and_neck_cancer#Cisplatin|Cisplatin]]
-|
-|-
-|[[Head_and_neck_cancer#Methotrexate_.28MTX.29|MTX]]
-|style="background-color:#00cd00"|Superior ORR
-|-
-|[http://jco.ascopubs.org/content/23/15/3562.long Gibson et al. 2005 (ECOG E1395)]
-|style="background-color:#00cd00"|Phase III
-|[[#Cisplatin_.26_Paclitaxel_.28CP.29|Cisplatin & Paclitaxel]]
 |style="background-color:#eeee00"|Seems not superior
 |-
-|[http://www.nejm.org/doi/full/10.1056/NEJMoa0802656 Vermorken et al. 2008]
+|}
-|style="background-color:#00cd00"|Phase III
+====Chemotherapy====
-|[[Head_and_neck_cancer#Cisplatin.2C_Fluorouracil.2C_Cetuximab|Cisplatin, Fluorouracil, Cetuximab]]
-|style="background-color:#ff0000"|Seems to have inferior OS
-|-
-|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70181-5/fulltext Vermorken et al. 2013 (SPECTRUM)]
-|style="background-color:#00cd00"|Phase III
-|[[#Cisplatin.2C_Fluorouracil.2C_Panitumumab|Cisplatin, Fluorouracil, Panitumumab]]
-|style="background-color:#ff0000"|Inferior PFS
-|-
-|}
-====Chemotherapy====
 *[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV once on day 1
-**'''ECOG E1395:''' [[Carboplatin (Paraplatin)]] AUC 6 IV once on day 1 could be substituted in patients who developed at least grade 2 neuropathy or renal impairment (creatinine clearance <50 mL/min; note: later in Gibson et al. 2005, it says that carboplatin was used for patients who had '''creatinine clearance ≤50 mL/min''')
+*[[Cetuximab (Erbitux)]] as follows:
-*[[Fluorouracil (5-FU)]] 1000 mg/m<sup>2</sup>/day IV continuous infusion on days 1 to 4 (total dose per cycle: 4000 mg/m<sup>2</sup>)
+**Cycle 1: 200 mg/m<sup>2</sup> IV over 120 minutes once on day 1, then 125 mg/m<sup>2</sup> IV over 60 minutes once per day on days 8, 15, 22
+**Subsequent cycles: 125 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1, 8, 15, 22
-====Supportive medications====
+'''28-day cycles'''
-*Details vary per reference
-*Pretreatment and posttreatment hydration and mannitol diuresis with cisplatin
-*"Standard antiemetic regimens"
-'''21-day cycle for up to 6 cycles (SPECTRUM) or indefinitely, see note below'''
+''Per physician discretion, patients with complete response (CR) could have treatment discontinued 2 cycles past the point at which CR was attained. Patients with partial response (PR) continued on treatment until there was evidence of CR or progression disease. Patients with stable disease (SD) could discontinue treatment after 6 cycles. Patients with progressive disease discontinued therapy.''
-''In '''ECOG E1395''', patients with complete response (CR) received at least 6 cycles or 2 cycles past the point at which CR was documented, whichever came later; patients with partial response (PR) continued on treatment until there was evidence of CR or progression disease; patients with stable disease (SD) could discontinue treatment after six cycles.''
 ===References===
-# Forastiere AA, Metch B, Schuller DE, Ensley JF, Hutchins LF, Triozzi P, Kish JA, McClure S, VonFeldt E, Williamson SK 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 Aug;10(8):1245-51. [http://jco.ascopubs.org/content/10/8/1245.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/1634913 PubMed]
+<!-- Presented in part at the 38th Annual Meeting of the American Society of Clinical Oncology, May 18-21, Orlando, FL, and the American Association for Cancer Research/National Cancer Institute/European Organisation for Research and Treatment of Cancer International Conference on Molecular Targets in Cancer Therapy, November 17-21, 2003, Boston, MA. -->
-# Gibson MK, Li Y, Murphy B, Hussain MH, DeConti RC, Ensley J, Forastiere AA; Eastern Cooperative Oncology Group. 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 May 20;23(15):3562-7. [http://jco.ascopubs.org/content/23/15/3562.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/15908667 PubMed]
+# Burtness B, Goldwasser MA, Flood W, Mattar B, Forastiere AA; Eastern Cooperative Oncology Group. 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 Dec 1;23(34):8646-54. [http://jco.ascopubs.org/content/23/34/8646.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/16314626 PubMed]
-# Vermorken JB, Mesia R, Rivera F, Remenar E, Kawecki A, Rottey S, Erfan J, Zabolotnyy D, Kienzer HR, Cupissol D, Peyrade F, Benasso M, Vynnychenko I, De Raucourt D, Bokemeyer C, Schueler A, Amellal N, Hitt R. Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med. 2008 Sep 11;359(11):1116-27. [http://www.nejm.org/doi/full/10.1056/NEJMoa0802656 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/18784101 PubMed]
-# Vermorken JB, Stöhlmacher-Williams J, Davidenko I, Licitra L, Winquist E, Villanueva C, Foa P, Rottey S, Skladowski K, Tahara M, Pai VR, Faivre S, Blajman CR, Forastiere AA, Stein BN, Oliner KS, Pan Z, Bach BA; SPECTRUM investigators. Cisplatin and fluorouracil with or without panitumumab in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck (SPECTRUM): an open-label phase 3 randomised trial. Lancet Oncol. 2013 Jul;14(8):697-710. Epub 2013 Jun 6. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70181-5/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23746666 PubMed]
-# Zhang L, Huang Y, Hong S, Yang Y, Yu G, Jia J, Peng P, Wu X, Lin Q, Xi X, Peng J, Xu M, Chen D, Lu X, Wang R, Cao X, Chen X, Lin Z, Xiong J, Lin Q, Xie C, Li Z, Pan J, Li J, Wu S, Lian Y, Yang Q, Zhao C. Gemcitabine plus cisplatin versus fluorouracil plus cisplatin in recurrent or metastatic nasopharyngeal carcinoma:a multicentre, randomised, open-label, phase 3 trial. Lancet. 2016 Aug 23. [Epub ahead of print] [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(16)31388-5/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/27567279 PubMed]
 ==Cisplatin, Fluorouracil, Cetuximab {{#subobject:efa517|Regimen=1}}==
@@ Line 1,414: / Line 1,513: @@
 |[http://www.nejm.org/doi/full/10.1056/NEJMoa0802656 Vermorken et al. 2008]
 |style="background-color:#00cd00"|Phase III
-|[[Head_and_neck_cancer#Cisplatin_.26_Fluorouracil_.28CF.29|Cisplatin & Fluorouracil]]
+|[[#CF|CF]]
 |style="background-color:#00cd00"|Seems to have superior OS
 |-
@@ Line 1,428: / Line 1,527: @@
 ===References===
-# Vermorken JB, Mesia R, Rivera F, Remenar E, Kawecki A, Rottey S, Erfan J, Zabolotnyy D, Kienzer HR, Cupissol D, Peyrade F, Benasso M, Vynnychenko I, De Raucourt D, Bokemeyer C, Schueler A, Amellal N, Hitt R. Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med. 2008 Sep 11;359(11):1116-27. [http://www.nejm.org/doi/full/10.1056/NEJMoa0802656 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/18784101 PubMed]
+# Vermorken JB, Mesia R, Rivera F, Remenar E, Kawecki A, Rottey S, Erfan J, Zabolotnyy D, Kienzer HR, Cupissol D, Peyrade F, Benasso M, Vynnychenko I, De Raucourt D, Bokemeyer C, Schueler A, Amellal N, Hitt R. Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med. 2008 Sep 11;359(11):1116-27. [http://www.nejm.org/doi/full/10.1056/NEJMoa0802656 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18784101 PubMed]
 ==Cisplatin, Fluorouracil, Panitumumab {{#subobject:6a95a4|Regimen=1}}==
@@ Line 1,444: / Line 1,543: @@
 |[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70181-5/fulltext Vermorken et al. 2013 (SPECTRUM)]
 |style="background-color:#00cd00"|Phase III
-|[[#Cisplatin_.26_Fluorouracil_.28CF.29|Cisplatin & Fluorouracil]]
+|[[#CF|CF]]
 |style="background-color:#00cd00"|Superior PFS
 |-
@@ Line 1,474: / Line 1,573: @@
 |[http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(16)31388-5/fulltext Zhang et al. 2016]
 |style="background-color:#00cd00"|Phase III
-|[[#Cisplatin_.26_Fluorouracil_.28CF.29|Cisplatin & Fluorouracil]]
+|[[#CF|CF]]
 |style="background-color:#00cd00"|Superior PFS
 |-
@@ Line 1,488: / Line 1,587: @@
 # Zhang L, Huang Y, Hong S, Yang Y, Yu G, Jia J, Peng P, Wu X, Lin Q, Xi X, Peng J, Xu M, Chen D, Lu X, Wang R, Cao X, Chen X, Lin Z, Xiong J, Lin Q, Xie C, Li Z, Pan J, Li J, Wu S, Lian Y, Yang Q, Zhao C. Gemcitabine plus cisplatin versus fluorouracil plus cisplatin in recurrent or metastatic nasopharyngeal carcinoma:a multicentre, randomised, open-label, phase 3 trial. Lancet. 2016 Aug 23. [Epub ahead of print] [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(16)31388-5/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/27567279 PubMed]
-==Cisplatin & Paclitaxel (CP) {{#subobject:976865|Regimen=1}}==
+==CP {{#subobject:976865|Regimen=1}}==
 {| class="wikitable" style="float:right; margin-left: 5px;"
 |-
 |[[#top|back to top]]
 |}
+CP: '''<u>C</u>'''isplatin and '''<u>P</u>'''aclitaxel
 ===Regimen {{#subobject:502e23|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
@@ Line 1,503: / Line 1,602: @@
 |[http://jco.ascopubs.org/content/23/15/3562.long Gibson et al. 2005 (ECOG E1395)]
 |style="background-color:#00cd00"|Phase III
-|[[#Cisplatin_.26_Fluorouracil_.28CF.29|Cisplatin & Fluorouracil]]
+|[[#CF|CF]]
 |style="background-color:#eeee00"|Seems not superior
 |-
@@ Line 1,513: / Line 1,612: @@
 ====Supportive medications====
-*Hydration and forced diuresis (no further details given) with cisplatin
+*Hydration and forced diuresis (no further details given) with [[Cisplatin (Platinol)]]
-*[[Dexamethasone (Decadron)]] 20 mg PO given twice, 12 and 6 hours prior to paclitaxel
+*[[Dexamethasone (Decadron)]] 20 mg PO given twice, 12 and 6 hours prior to [[Paclitaxel (Taxol)]]
-*[[Diphenhydramine (Benadryl)]] (no dose specified) IV within 60 minutes prior to paclitaxel
+*[[Diphenhydramine (Benadryl)]] (no dose specified) IV within 60 minutes prior to [[Paclitaxel (Taxol)]]
-*H2 receptor antagonist (no further details given) IV within 60 minutes prior to paclitaxel
+*H2 receptor antagonist (no further details given) IV within 60 minutes prior to [[Paclitaxel (Taxol)]]
 '''21-day cycles'''
@@ Line 1,523: / Line 1,622: @@
 ===References===
-# Gibson MK, Li Y, Murphy B, Hussain MH, DeConti RC, Ensley J, Forastiere AA; Eastern Cooperative Oncology Group. 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 May 20;23(15):3562-7. [http://jco.ascopubs.org/content/23/15/3562.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/15908667 PubMed]
+# Gibson MK, Li Y, Murphy B, Hussain MH, DeConti RC, Ensley J, Forastiere AA; Eastern Cooperative Oncology Group. 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 May 20;23(15):3562-7. [http://jco.ascopubs.org/content/23/15/3562.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/15908667 PubMed]
 ==Gemcitabine (Gemzar) {{#subobject:c3cf55|Regimen=1}}==
@@ Line 1,552: / Line 1,651: @@
 ===References===
-# Zhang L, Zhang Y, Huang PY, Xu F, Peng PJ, Guan ZZ. 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 Jan;61(1):33-8. Epub 2007 Mar 20. [http://link.springer.com/article/10.1007%2Fs00280-007-0441-8 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/17909810 PubMed]
+# Zhang L, Zhang Y, Huang PY, Xu F, Peng PJ, Guan ZZ. 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 Jan;61(1):33-8. Epub 2007 Mar 20. [http://link.springer.com/article/10.1007%2Fs00280-007-0441-8 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/17909810 PubMed]
 ==Methotrexate (MTX) {{#subobject:dc3e62|Regimen=1}}==
@@ Line 1,564: / Line 1,663: @@
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
 |[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
+|-
+|rowspan=2|[http://jco.ascopubs.org/content/10/8/1245.long Forastiere et al. 1992]
+|rowspan=2 style="background-color:#00cd00"|Phase III
+|[[Head_and_neck_cancer#Carboplatin_.26_Fluorouracil|Carboplatin & Fluorouracil]]
+|style="background-color:#ff0000"|Seems to have inferior ORR
+|-
+|[[#CF|CF]]
+|style="background-color:#ff0000"|Inferior ORR
+|-
+|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)70124-5/fulltext Machiels et al. 2015 (LUX-Head & Neck 1)]
+|style="background-color:#00cd00"|Phase III
+|[[#Afatinib_.28Gliotrif.29|Afatinib]]
+|style="background-color:#ff0000"|Seems to have inferior PFS
+|-
+|}
+====Chemotherapy====
+*[[Methotrexate (MTX)]] 40 mg/m<sup>2</sup> IV once per week
+====Supportive medications====
+*"Standard antiemetic regimens"
+===References===
+# Forastiere AA, Metch B, Schuller DE, Ensley JF, Hutchins LF, Triozzi P, Kish JA, McClure S, VonFeldt E, Williamson SK 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 Aug;10(8):1245-51. [http://jco.ascopubs.org/content/10/8/1245.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/1634913 PubMed]
+# Machiels JP, Haddad RI, Fayette J, Licitra LF, Tahara M, Vermorken JB, Clement PM, Gauler T, Cupissol D, Grau JJ, Guigay J, Caponigro F, de Castro G Jr, de Souza Viana L, Keilholz U, Del Campo JM, Cong XJ, Ehrnrooth E, Cohen EE; LUX-H&N 1 investigators. 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 May;16(5):583-94. Epub 2015 Apr 16. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)70124-5/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25892145 PubMed]
+==Pembrolizumab (Keytruda) {{#subobject:10dd66|Regimen=1}}==
+{| class="wikitable" style="float:right; margin-left: 5px;"
+|-
+|[[#top|back to top]]
+|}
+===Regimen {{#subobject:159704|Variant=1}}===
+{| border="1" style="text-align:center;" !align="left"
+|'''Study'''
+|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |-
-|rowspan=2|[http://jco.ascopubs.org/content/10/8/1245.long Forastiere et al. 1992]
+|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(16)30066-3/fulltext Seiwert et al. 2016 (KEYNOTE-012)]
-|rowspan=2 style="background-color:#00cd00"|Phase III
+|style="background-color:#eeee00"|Phase Ib, >20 pts
-|[[Head_and_neck_cancer#Carboplatin_.26_Fluorouracil|Carboplatin & Fluorouracil]]
-|style="background-color:#ff0000"|Seems to have inferior ORR
-|-
-|[[Head_and_neck_cancer#Cisplatin_.26_Fluorouracil_.28CF.29|Cisplatin & Fluorouracil]]
-|style="background-color:#ff0000"|Inferior ORR
-|-
-|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)70124-5/fulltext Machiels et al. 2015 (LUX-Head & Neck 1)]
-|style="background-color:#00cd00"|Phase III
-|[[#Afatinib_.28Gliotrif.29|Afatinib]]
-|style="background-color:#ff0000"|Seems to have inferior PFS
 |-
 |}
-====Chemotherapy====
+====Immunotherapy====
-*[[Methotrexate (MTX)]] 40 mg/m<sup>2</sup> IV once per week
+*[[Pembrolizumab (Keytruda)]] 10 mg/kg IV once on day 1
-====Supportive medications====
-*"Standard antiemetic regimens"
-===References===
+'''2-week cycles until progression, intolerance, or maximum of 24 months'''
-# Forastiere AA, Metch B, Schuller DE, Ensley JF, Hutchins LF, Triozzi P, Kish JA, McClure S, VonFeldt E, Williamson SK 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 Aug;10(8):1245-51. [http://jco.ascopubs.org/content/10/8/1245.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/1634913 PubMed]
-# Machiels JP, Haddad RI, Fayette J, Licitra LF, Tahara M, Vermorken JB, Clement PM, Gauler T, Cupissol D, Grau JJ, Guigay J, Caponigro F, de Castro G Jr, de Souza Viana L, Keilholz U, Del Campo JM, Cong XJ, Ehrnrooth E, Cohen EE; LUX-H&N 1 investigators. 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 May;16(5):583-94. Epub 2015 Apr 16. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)70124-5/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25892145 PubMed]
-==Pembrolizumab (Keytruda) {{#subobject:10dd66|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
-===Regimen {{#subobject:159704|Variant=1}}===
-''To be completed''
 ===References===
-# Seiwert TY, Burtness B, Mehra R, Weiss J, Berger R, Eder JP, Heath K, McClanahan T, Lunceford J, Gause C, Cheng JD, Chow LQ. 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 Jul;17(7):956-65. Epub 2016 May 27. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(16)30066-3/fulltext link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/27247226 PubMed]
+# Seiwert TY, Burtness B, Mehra R, Weiss J, Berger R, Eder JP, Heath K, McClanahan T, Lunceford J, Gause C, Cheng JD, Chow LQ. 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 Jul;17(7):956-65. Epub 2016 May 27. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(16)30066-3/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/27247226 PubMed]
 [[Category:Chemotherapy regimens]]
 [[Category:Solid oncology regimens]]

Difference between revisions of "Head and neck cancer"

Revision as of 03:03, 4 November 2016

Adjuvant chemotherapy & radiation therapy

Cisplatin & RT

Regimen #1

Chemoradiotherapy

Supportive medications

Regimen #2

Chemoradiotherapy

Supportive medications

Regimen #3

Chemoradiotherapy

Supportive medications

References

Radiation therapy

Regimen

References

Locally advanced disease, chemotherapy & radiation therapy

Carboplatin & RT -> Carboplatin & Fluorouracil

Regimen

Chemoradiotherapy

Chemotherapy

References

Carboplatin, Fluorouracil, RT

Regimen

Chemoradiotherapy

References

Carboplatin, Paclitaxel, RT

Regimen #1, accelerated hyperfractionated RT

Chemoradiotherapy

Regimen #2, standard RT

Chemoradiotherapy

Supportive medications

References

Cetuximab & RT

Regimen

Chemoradiotherapy

Supportive medications

References

CF -> Carboplatin & RT

Regimen

Chemotherapy

Chemoradiotherapy

References

CF -> Cisplatin & RT

Regimen

Chemotherapy

Chemoradiotherapy

References

CF & RT

Regimen #1

Chemotherapy

Radiotherapy

Regimen #2

Chemoradiotherapy

References

CF -> RT

Regimen #1

Chemotherapy

Radiotherapy

Regimen #2

Chemotherapy

Radiotherapy

Regimen #3

Chemotherapy

Supportive medications

Radiotherapy

Regimen #4

Chemotherapy

Supportive medications

Radiotherapy

References

Cisplatin & RT

Regimen #1

Chemoradiotherapy

Regimen #2

Chemoradiotherapy

Regimen #3

Chemoradiotherapy

References