Induction Chemotherapy for Head and Neck Cancer: Will History Repeat Itself?

Author: Athanassios Argiris MD1
View More View Less
  • 1 Division of Hematology-Oncology, University of Pittsburgh, Pittsburgh, Pennsylvania

Locally advanced squamous cell head and neck cancer remains a therapeutic challenge for multidisciplinary teams. Despite high objective response rates, induction chemotherapy has not resulted in tangible benefit in multiple randomized trials. In recent years, as most evidence solidified the role of concurrent chemotherapy and radiation as either primary or postoperative therapy for locally advanced head and neck cancer, induction chemotherapy fell out of scope and practice. The failure of older randomized trials to show a survival benefit from induction chemotherapy can be attributed to several factors. It is possible that the predominance of locoregional failure did not allow any added benefit from better systemic control to translate into a survival advantage. Alternatively, seemingly active chemotherapy regimens may have been suboptimal. Nevertheless, recent developments have altered our perception of head and neck cancer and its treatment. Locoregional control has dramatically improved with concurrent chemoradiotherapy. Of note is that none of the previously conducted randomized trials of induction chemotherapy used concurrent chemoradiotherapy in the control arm. Moreover, we witnessed the development of better combination regimens that improved efficacy in the induction setting. The previously standard cisplatin/5-fluoruracil (5-FU) combination is being replaced by the triple combination of taxane/cisplatin/5-FU. Randomized trials showed that increased activity with the triplet regimen resulted in improved long-term disease control and survival. Finally, cetuximab, an active epidermal growth factor receptor inhibitor, is entering clinical practice and is expected to change the standard of therapy. With the emergence of more efficacious systemic therapies, the role of induction therapy warrants reevaluation. A number of randomized trials are planned or currently ongoing to investigate concurrent chemoradiotherapy with or without induction. These trials are anticipated to redefine the role of induction chemotherapy for head and neck cancer.

Correspondence: Athanassios Argiris, MD, Division of Hematology-Oncology, University of Pittsburgh, 5150 Centre Avenue, UPMC Cancer Pavilion, 5th floor, Pittsburgh, PA 15232. E-mail: argirisae@upmc.edu
  • 1

    Jemal A, Tiwari RC, Murray T et al.. Cancer statistics, 2004. CA Cancer J Clin 2004;54:829.

  • 2

    Kramer S, Gelber RD, Snow JB et al.. Combined radiation therapy and surgery in the management of advanced head and neck cancer: final report of study 73-03 of the Radiation Therapy Oncology Group. Head Neck Surg 1987;10:1930.

    • Search Google Scholar
    • Export Citation
  • 3

    Taylor SGT. Why has so much chemotherapy done so little in head and neck cancer? J Clin Oncol 1987;5:13.

  • 4

    Rosenthal DI, Pistenmaa DA, Glatstein E. A review of neoadjuvant chemotherapy for head and neck cancer: partially shrunken tumors may be both leaner and meaner. Int J Radiat Oncol Biol Phys 1994;28:315320.

    • Search Google Scholar
    • Export Citation
  • 5

    Argiris A. Update on chemoradiotherapy for head and neck cancer. Curr Opin Oncol 2002;14:323329.

  • 6

    Argiris A, Jayaram P, Pichardo D. Revisiting induction chemotherapy for head and neck cancer. Oncology 2005, 19 (in press).

  • 7

    Hitt R, Lopez-Pousa A, Rodriguez M et al.. Phase III study comparing cisplatin (P) & 5-fluoruracil (F) versus P, F and paclitaxel (T) as induction therapy in locally advanced head & neck cancer (LAHNC) (Abstr). Proc Am Soc Clin Oncol 2003;22:A1997.

    • Search Google Scholar
    • Export Citation
  • 8

    Vermorken JB, Remenar E, Van Herpen C et al.. Standard cisplatin/infusional 5-fluorouracil (PF) vs docetaxel (T) plus PF (TPF) as neoadjuvant chemotherapy for nonresectable locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN): a phase III trial of the EORTC Head and Neck Cancer Group (EORTC #24971) (Abstr). Proc Am Soc Clin Oncol 2004;22:A5508.

    • Search Google Scholar
    • Export Citation
  • 9

    Kish J, Drelichman A, Jacobs J et al.. Clinical trial of cisplatin and 5-FU infusion as initial treatment for advanced squamous cell carcinoma of the head and neck. Cancer Treat Rep 1982;66:471474.

    • Search Google Scholar
    • Export Citation
  • 10

    Nadeem A, Desai S, Chougule P et al.. Decreased distant recurrence and preserved local control using dose dense induction weekly paclitaxel (P) and carboplatin (C) followed by concurrent paclitaxel, carboplatin and radiotherapy (CRT) in locally advanced head and neck squamous cell cancers (HN-SCC) (Abstr). Proc Am Soc Clin Oncol 2004;22:A5545.

    • Search Google Scholar
    • Export Citation
  • 11

    Haraf DJ, Rosen FR, Stenson K et al.. Induction chemotherapy followed by concomitant TFHX chemoradiotherapy with reduced dose radiation in advanced head and neck cancer. Clin Cancer Res 2003;9:59365943.

    • Search Google Scholar
    • Export Citation
  • 12

    Vokes EE, Stenson K, Rosen FR et al.. Weekly carboplatin and paclitaxel followed by concomitant paclitaxel, fluorouracil, and hydroxyurea chemoradiotherapy: curative and organ-preserving therapy for advanced head and neck cancer. J Clin Oncol 2003;21:320326.

    • Search Google Scholar
    • Export Citation
  • 13

    Fornari G, Artusio E, Mairone L et al.. Paclitaxel and carboplatin in neo-adjuvant and concomitant chemoradiotherapy in locally advanced head and neck squamous cell carcinoma. Tumori 2002;88:489494.

    • Search Google Scholar
    • Export Citation
  • 14

    Cmelak A, Murphy BA, Burkey B et al.. Induction chemotherapy (IC) followed by concurrent chemoradiation (CCR) for organ preservation (OP) in locally advanced squamous head and neck cancer (SHNC): results of a Phase II trial (Abstr). Proc Am Soc Clin Oncol 2003;22:A2016.

    • Search Google Scholar
    • Export Citation
  • 15

    Machtay M, Rosenthal DI, Hershock D et al.. Organ preservation therapy using induction plus concurrent chemoradiation for advanced resectable oropharyngeal carcinoma: a University of Pennsylvania Phase II Trial. J Clin Oncol 2002;20:39643971.

    • Search Google Scholar
    • Export Citation
  • 16

    Dunphy FR, Dunleavy TL, Harrison BR et al.. Induction paclitaxel and carboplatin for patients with head and neck carcinoma. Analysis of 62 patients treated between 1994 and 1999. Cancer 2001;91:940948.

    • Search Google Scholar
    • Export Citation
  • 17

    Schoffski P, Catimel G, Planting AS et al.. Docetaxel and cisplatin: an active regimen in patients with locally advanced, recurrent or metastatic squamous cell carcinoma of the head and neck. Results of a phase II study of the EORTC Early Clinical Studies Group. Ann Oncol 1999;10:119122.

    • Search Google Scholar
    • Export Citation
  • 18

    Mel JR, Rodriguez R, Constela M et al.. Phase II study of docetaxel and cisplatin as induction chemotherapy in locally advanced squamous cell cacinoma of the head and neck: preliminary results. Proc Am Soc Clin Oncol (Abstr) 1999;18:A1549.

    • Search Google Scholar
    • Export Citation
  • 19

    Cruz JJ, Fonseca E, Garcia Gomez J et al.. Randomized phase II, multicenter trial of induction chemotherapy in patients with locally advanced head and neck carcinoma (LA-HNC). Docetaxel plus cisplatin (DP) versus cisplatin plus 5-FU (PF): interim results. Proc Am Soc Clin Oncol 2002;21:A920.

    • Search Google Scholar
    • Export Citation
  • 20

    Hitt R, Paz-Ares L, Brandariz A et al.. 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;13:16651673.

    • Search Google Scholar
    • Export Citation
  • 21

    Schrijvers D, Van Herpen C, Kerger J et al.. Docetaxel, cisplatin and 5-fluorouracil in patients with locally advanced unresectable head and neck cancer: a phase I-II feasibility study. Ann Oncol 2004;15:638645.

    • Search Google Scholar
    • Export Citation
  • 22

    Colevas AD, Norris CM, Tishler RB et al.. Phase I/II trial of outpatient docetaxel, cisplatin, 5-fluorouracil, leucovorin (opTPFL) as induction for squamous cell carcinoma of the head and neck (SCCHN). Am J Clin Oncol 2002;25:153159.

    • Search Google Scholar
    • Export Citation
  • 23

    Posner MR, Glisson B, Frenette G et al.. Multicenter phase I-II trial of docetaxel, cisplatin, and fluorouracil induction chemotherapy for patients with locally advanced squamous cell cancer of the head and neck. J Clin Oncol 2001;19:10961104.

    • Search Google Scholar
    • Export Citation
  • 24

    Janinis J, Papadakou M, Panagos G et al.. Sequential chemoradiotherapy with docetaxel, cisplatin, and 5- fluorouracil in patients with locally advanced head and neck cancer. Am J Clin Oncol 2001;24:227231.

    • Search Google Scholar
    • Export Citation
  • 25

    Colevas AD, Norris CM, Tishler RB et al.. Phase II trial of docetaxel, cisplatin, fluorouracil, and leucovorin as induction for squamous cell carcinoma of the head and neck. J Clin Oncol 1999;17:35033511.

    • Search Google Scholar
    • Export Citation
  • 26

    Colevas AD, Busse PM, Norris CM et al.. Induction chemotherapy with docetaxel, cisplatin, fluorouracil, and leucovorin for squamous cell carcinoma of the head and neck: a phase I/II trial. J Clin Oncol 1998;16:13311339.

    • Search Google Scholar
    • Export Citation
  • 27

    Posner MR, Lefebvre JL. Docetaxel induction therapy in locally advanced squamous cell carcinoma of the head and neck. Br J Cancer 2003;88:1117.

    • Search Google Scholar
    • Export Citation
  • 28

    Shin DM, Glisson BS, Khuri FR et al.. Phase II trial of paclitaxel, ifosfamide, and cisplatin in patients with recurrent head and neck squamous cell carcinoma. J Clin Oncol 1998;16:13251330.

    • Search Google Scholar
    • Export Citation
  • 29

    Shin DM, Khuri FR, Glisson BS et al.. Phase II study of paclitaxel, ifosfamide, and carboplatin in patients with recurrent or metastatic head and neck squamous cell carcinoma. Cancer 2001;91:13161323.

    • Search Google Scholar
    • Export Citation
  • 30

    Shin DM, Glisson BS, Khuri FR et al.. Phase II study of induction chemotherapy with paclitaxel, ifosfamide, and carboplatin (TIC) for patients with locally advanced squamous cell carcinoma of the head and neck. Cancer 2002;95:322230.

    • Search Google Scholar
    • Export Citation
  • 31

    Khuri F, Gillenwater A, Diaz E et al.. Pilot trial of paclitaxel, ifosfamide and cisplatin (TIP) as induction or exclusive therapy for intermediate to advanced laryngeal cancer (Abstr). Proc Am Soc Clin Oncol 2002;21:A906.

    • Search Google Scholar
    • Export Citation
  • 32

    Kies MS, Lewin JS, Diaz EM et al.. Definitive treatment of intermediate stage laryngeal squamous cell (SCC/L) cancer with chemotherapy (CT). Proc Am Soc Clin Oncol 2004;22:A5533.

    • Search Google Scholar
    • Export Citation
  • 33

    Pignon JP, Bourhis J, Domenge C et al.. Chemotherapy added to locoregional treatment for head and neck squamous-cell carcinoma: three meta-analyses of updated individual data. MACH-NC Collaborative Group. Meta-Analysis of Chemotherapy on Head and Neck Cancer. Lancet 2000;355:949955.

    • Search Google Scholar
    • Export Citation
  • 34

    De Andres L, Brunet J, Lopez-Pousa A et al.. Randomized trial of neoadjuvant cisplatin and fluorouracil versus carboplatin and fluorouracil in patients with stage IV-M0 head and neck cancer. J Clin Oncol 1995;13:14931500.

    • Search Google Scholar
    • Export Citation
  • 35

    Schuller DE, Stein DW, Metch B. Analysis of treatment failure patterns. A Southwest Oncology Group Study. Arch Otolaryngol Head Neck Surg 1989:115:834836.

    • Search Google Scholar
    • Export Citation
  • 36

    Paccagnella A, Orlando A, Marchiori C et al.. Phase III trial of initial chemotherapy in stage III or IV head and neck cancers: a study by the Gruppo di Studio sui Tumori della Testa e del Collo. J Natl Cancer Inst 1994;86:265272.

    • Search Google Scholar
    • Export Citation
  • 37

    Domenge C, Hill C, Lefebvre JL et al.. Randomized trial of neoadjuvant chemotherapy in oropharyngeal carcinoma. French Groupe d'Etude des Tumeurs de la Tete et du Cou (GETTEC). Br J Cancer 2000;83:15941598.

    • Search Google Scholar
    • Export Citation
  • 38

    Lewin F, Damber L, Jonsson H et al.. Neoadjuvant chemotherapy with cisplatin and 5-fluorouracil in advanced squamous cell carcinoma of the head and neck: a randomized phase III study. Radiother Oncol 1997;43:2328.

    • Search Google Scholar
    • Export Citation
  • 39

    Dalley D, Beller E, Aroney R et al.. The value of chemotherapy (CT) prior to definitive local therapy (DLT) in patients with locally advanced squamous cell carcinoma (SCC) of the head and neck (HN) (Abstr). Proc Annu Meet Am Assoc Cancer Res 1995;14:A856.

    • Search Google Scholar
    • Export Citation
  • 40

    Depondt J, Gehanno P, Martin M et al.. Neoadjuvant chemotherapy with carboplatin/5-fluorouracil in head and neck cancer. Oncology 1993;50(suppl 2):2327.

    • Search Google Scholar
    • Export Citation
  • 41

    Licitra L, Grandi C, Guzzo M et al.. Primary chemotherapy in resectable oral cavity squamous cell cancer: a randomized controlled trial. J Clin Oncol 2003;21:327333.

    • Search Google Scholar
    • Export Citation
  • 42

    Taylor SGt, Murthy AK, Vannetzel JM 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;12:385395.

    • Search Google Scholar
    • Export Citation
  • 43

    Adelstein D, Saxton J, Lavertu P et al.. A phase III randomized trial comparing concurrent chemotherapy (CT) and radiation therapy (RT) with RT alone in resectable stage III and IV squamous cell head and neck cancer (SCHNC): preliminary results, In: 4th International Conference on Head and Neck Cancer. Toronto, Canada, The Society of Head and Neck Surgeons and American Society of Head and Neck Surgery; 1996.

    • Search Google Scholar
    • Export Citation
  • 44

    Forastiere AA, Goepfert H, Maor M et al.. Concurrent chemotherapy and radiotherapy for organ preservation in advanced laryngeal cancer. N Engl J Med 2003;34:20912098.

    • Search Google Scholar
    • Export Citation
  • 45

    Calais G, Alfonsi M, Bardet E et al.. Randomized trial of radiation therapy versus concomitant chemotherapy and radiation therapy for advanced-stage orophaynx carcinoma. J Natl Cancer Inst 1999;91:20812086.

    • Search Google Scholar
    • Export Citation
  • 46

    Al-Sarraf M, LeBlanc M, Giri P et al.. Superiority of chemoradiotherapy vs radiotherapy in patients with locally advanced nasopharyngeal cancer preliminary results of intergroup (0099) (SWOG 8892, RTOG 8817, ECOG 2388) randomized study (Abstr #882). Proc Am Soc Clin Oncol 1996;15:313.

    • Search Google Scholar
    • Export Citation
  • 47

    Adelstein DJ, Li Y, Adams GL et al.. An intergroup phase III comparison of standard radiation therapy and two schedules of concurrent chemoradiotherapy in patients with unresectable squamous cell head and neck cancer. J Clin Oncol 2003;21:9298.

    • Search Google Scholar
    • Export Citation
  • 48

    Al-Sarraf M, LeBlanc M, Giri PG et al.. Chemoradiotherapy versus radiotherapy in patients with advanced nasopharyngeal cancer: phase III randomized Intergroup study 0099. J Clin Oncol 1998;16:13101317.

    • Search Google Scholar
    • Export Citation
  • 49

    Cooper JS, Pajak TF, Forastiere AA et al.. Postoperative concurrent radiotherapy and chemotherapy for high-risk squamous-cell carcinoma of the head and neck. N Engl J Med 2004;350:19371944.

    • Search Google Scholar
    • Export Citation
  • 50

    Bernier J, Domenge C, Ozsahin M et al.. Postoperative irradiation with or without concomitant chemotherapy for locally advanced head and neck cancer. N Engl J Med 2004;350:19451952.

    • Search Google Scholar
    • Export Citation
  • 51

    Adelstein DJ, Saxton JP, Lavertu P et al.. Maximizing local control and organ preservation in stage IV squamous cell head and neck cancer With hyperfractionated radiation and concurrent chemotherapy. J Clin Oncol 2002; 20:14051410.

    • Search Google Scholar
    • Export Citation
  • 52

    Vokes EE, Kies MS, Haraf DJ et al.. Concomitant chemoradiotherapy as primary therapy for locoregionally advanced head and neck cancer. J Clin Oncol 2000;18:16521661.

    • Search Google Scholar
    • Export Citation
  • 53

    Argiris A, Haraf DJ, Kies MS et al.. Intensive concurrent chemoradiotherapy for head and neck cancer with 5-fluorouracil- and hydroxyurea-based regimens: reversing a pattern of failure. Oncologist 2003;8:350360.

    • Search Google Scholar
    • Export Citation
  • 54

    Induction chemotherapy plus radiation compared with surgery plus radiation in patients with advanced laryngeal cancer. The Department of Veterans Affairs Laryngeal Cancer Study Group. N Engl J Med 1991;324:16851690.

    • Search Google Scholar
    • Export Citation
  • 55

    Lefebvre JL, Chevalier D, Luboinski B et al.. Larynx preservation in pyriform sinus cancer: preliminary results of a European Organization for Research and Treatment of Cancer phase III trial. EORTC Head and Neck Cancer Cooperative Group. J Natl Cancer Inst 1996;88:890899.

    • Search Google Scholar
    • Export Citation
  • 56

    Richard JM, Sancho-Garnier H, Pessey JJ et al.. Randomized trial of induction chemotherapy in larynx carcinoma. Oral Oncol 1998;34:224228.

  • 57

    Lefebvre JL, Wolf G, Luboinski B et al.. Meta-analysis of chemotherapy in head and neck cancer (MACH-NC) (2) larynx preservation using neoadjuvant chemotherapy (CT) in laryngeal and hypopharyngeal carcinoma (Abstr). Proc Am Soc Clin Oncol 1998;17:A1473.

    • Search Google Scholar
    • Export Citation
  • 58

    Bonner JA, Giralt J, Harari PM et al.. Cetuximab prolongs survival in patients with locoregionally advanced squamous cell carcinoma of head and neck: A phase III study of high dose radiation therapy with or without cetuximab (Abstr). Proc Am Soc Clin Oncol 2004;22:A5507.

    • Search Google Scholar
    • Export Citation
  • 59

    Urba SG, Moon J, Giri PG et al.. Organ preservation for advanced resectable cancer of the base of tongue and hypopharynx: a Southwest Oncology Group Trial. J Clin Oncol 2005;23:8895.

    • Search Google Scholar
    • Export Citation
  • 60

    Hainsworth JD, Meluch AA, McClurkan S et al.. Induction paclitaxel, carboplatin, and infusional 5-FU followed by concurrent radiation therapy and weekly paclitaxel/carboplatin in the treatment of locally advanced head and neck cancer: a phase II trial of the Minnie Pearl Cancer Research Network. Cancer J 2002;8:311321.

    • Search Google Scholar
    • Export Citation
  • 61

    Spaulding MB, Fischer SG, Wolf GT. Tumor response, toxicity, and survival after neoadjuvant organ-preserving chemotherapy for advanced laryngeal carcinoma. The Department of Veterans Affairs Cooperative Laryngeal Cancer Study Group. J Clin Oncol 1994;12:15921599.

    • Search Google Scholar
    • Export Citation
All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 288 67 3
PDF Downloads 194 59 5
EPUB Downloads 0 0 0