Skip to main content
Log in

The Cisplatin Total Dose and Concomitant Radiation in Locoregionally Advanced Head and Neck Cancer: Any Recent Evidence for Dose Efficacy?

  • Head and Neck Cancer (L Licitra, Section Editor)
  • Published:
Current Treatment Options in Oncology Aims and scope Submit manuscript

Opinion statement

Concurrent chemoradiotherapy (CRT) with high-dose (100 mg/m2), single-agent cisplatin is considered the standard of care for locoregionally advanced head and neck cancer (LAHNC). Poor compliance often due to significant treatment-related toxicities observed during CRT regimen has stimulated research efforts to examine for evidence of the optimal cumulative cisplatin dose and schedule. The findings from this systematic literature review demonstrate that there are insufficient prospective, randomized controlled data to determine the optimal total dose (and schedule) of cisplatin to administer concomitantly with radiotherapy in the treatment of LAHNC. Given the clinical challenges associated with administering concurrent CRT with single-agent high-dose cisplatin, as well as the long-term toxicities accompanying this treatment, an examination of the available literature for evidence of dose efficacy is of continued clinical interest. Moving forward, it is critical that researchers include complete descriptions of key disease and treatment variables (i.e. treatment compliance and HPV status) to inform and strengthen clinical decisions. The substantial heterogeneity of LAHNC has led to the focus of recent research efforts to risk-stratify using a combination of clinical and molecular markers (e.g. HPV status). Thus, the optimal total dose (and schedule) of cisplatin may need to be modified to reflect the specific characteristics of the individual patient subpopulations being treated. At present, CRT remains the standard of care for LAHNC, but this field is rapidly evolving. National and international clinical trials are ongoing to evaluate treatment de-intensification in favourable risk patient subsets and treatment intensification in poor-risk patient subsets, these will provide evidence-based guidance to individualize therapy with the ultimate goal of improving patient outcomes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Bourhis J, Overgaard J, Audry H, et al. Hyperfractionated or accelerated radiotherapy in head and neck cancer: a meta-analysis. Lancet. 2006;368(9538):843–54.

    Article  PubMed  Google Scholar 

  2. Gupta T, Kannan S, Ghosh-Laskar S, Agarwal JP. Concomitant chemoradiotherapy versus altered fractionation radiotherapy in the radiotherapeutic management of locoregionally advanced head and neck squamous cell carcinoma: an adjusted indirect comparison meta-analysis. Head Neck. 2015;37(5):670–6.

    Article  PubMed  Google Scholar 

  3. 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(19):1945–52.

    Article  CAS  PubMed  Google Scholar 

  4. 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(19):1937–44.

    Article  PubMed  Google Scholar 

  5. Forastiere AA, Goepfert H, Maor M, et al. Concurrent chemotherapy and radiotherapy for organ preservation in advanced laryngeal cancer. N Engl J Med. 2003;349(22):2091–8.

    Article  CAS  PubMed  Google Scholar 

  6. Pignon JP, le Maitre A, Maillard E, Bourhis J, Group M-NC. Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): an update on 93 randomised trials and 17,346 patients. Radiother Oncol. 2009;92(1):4–14.

    Article  PubMed  Google Scholar 

  7. • Strojan P, Vermorken JB, Beitler JJ, et al. Cumulative cisplatin dose in concurrent chemoradiotherapy for head and neck cancer: a systematic review. Head Neck. 2016;38(Suppl 1):E2151–8. A systematic review of the literature published between 1978 and 2014 evaluating optimal dose and timing of cisplatin in both definitive chemoradiotherapy (CRT) and postoperative CRT for patients with locoregionally advanced squamous cell carcinoma of the head and neck. These authors highlight several of the limitations presented in the current paper

  8. Wong SJ, Harari PM, Garden AS, et al. Longitudinal Oncology Registry of Head and Neck Carcinoma (LORHAN): analysis of chemoradiation treatment approaches in the United States. Cancer. 2011;117(8):1679–86.

    Article  PubMed  Google Scholar 

  9. Trotti A, Pajak TF, Gwede CK, et al. TAME: development of a new method for summarising adverse events of cancer treatment by the Radiation Therapy Oncology Group. Lancet Oncol. 2007;8(7):613–24.

    Article  PubMed  Google Scholar 

  10. Homma A, Inamura N, Oridate N, et al. Concomitant weekly cisplatin and radiotherapy for head and neck cancer. Jpn J Clin Oncol. 2011;41(8):980–6.

    Article  PubMed  Google Scholar 

  11. Ang KK. Concurrent radiation chemotherapy for locally advanced head and neck carcinoma: are we addressing burning subjects? Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2004;22(23):4657–9.

    Article  Google Scholar 

  12. Rampino M, Ricardi U, Munoz F, et al. Concomitant adjuvant chemoradiotherapy with weekly low-dose cisplatin for high-risk squamous cell carcinoma of the head and neck: a phase II prospective trial. Clin Oncol (R Coll Radiol). 2011;23(2):134–40.

    Article  CAS  Google Scholar 

  13. Tsan DL, Lin CY, Kang CJ, et al. The comparison between weekly and three-weekly cisplatin delivered concurrently with radiotherapy for patients with postoperative high-risk squamous cell carcinoma of the oral cavity. Radiat Oncol. 2012;7:215.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Kunieda F, Kiyota N, Tahara M, et al. Randomized phase II/III trial of post-operative chemoradiotherapy comparing 3-weekly cisplatin with weekly cisplatin in high-risk patients with squamous cell carcinoma of head and neck: Japan Clinical Oncology Group Study (JCOG1008). Jpn J Clin Oncol. 2014;44(8):770–4.

    Article  PubMed  Google Scholar 

  15. •• Ang KK, Zhang Q, Rosenthal DI, et al. 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. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2014;32(27):2940–50. A phase III randomized trial RTOG0522 comparing CRT (with single-agent, cisplatin 100mg/m2) with and without cetuximab in LAHNC. This trial randomized 891 patients, captured HPV status for the oropharyngeal subset and included data on survival, disease-related and toxicity outcomes

  16. Arias F, Asin G, Uzcanga MI, et al. Final results of a phase II single-institutional trial with hyperfractionated radiation therapy (HFX) and four-weekly continuous cisplatin in locally advanced head and neck carcinoma. Clin Transl Oncol. 2014;16(6):555–60.

    Article  CAS  PubMed  Google Scholar 

  17. Ghosh-Laskar S, Kalyani N, Gupta T, et al. Conventional radiotherapy versus concurrent chemoradiotherapy versus accelerated radiotherapy in locoregionally advanced carcinoma of head and neck: results of a prospective randomized trial. Head Neck. 2016;38(2):202–7.

    Article  PubMed  Google Scholar 

  18. Mesia R, Henke M, Fortin A, et al. Chemoradiotherapy with or without panitumumab in patients with unresected, locally advanced squamous-cell carcinoma of the head and neck (CONCERT-1): a randomised, controlled, open-label phase 2 trial. Lancet Oncol. 2015;16(2):208–20.

    Article  CAS  PubMed  Google Scholar 

  19. •• Nguyen-Tan PF, Zhang Q, Ang KK, et al. Randomized phase III trial to test accelerated versus standard fractionation in combination with concurrent cisplatin for head and neck carcinomas in the Radiation Therapy Oncology Group 0129 trial: long-term report of efficacy and toxicity. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2014;32(34):3858–67. A phase III randomized trial RTOG0129 comparing the administration of accelerated versus conventional radiotherapy regimens administered concurrently with high-dose cisplatin (100mg/m2). Detailed treatment compliance data are provided. Multiple outcomes evaluated included OS, PFS, LRF and DM, as well as toxicity data

  20. Rodriguez CP, Adelstein DJ, Rybicki LA, et al. Randomized phase III study of 2 cisplatin-based chemoradiation regimens in locally advanced head and neck squamous cell carcinoma: impact of changing disease epidemiology on contemporary trial design. Head Neck. 2015;37(11):1583–9.

    Article  PubMed  Google Scholar 

  21. • Driessen CM, Janssens GO, van der Graaf WT, et al. Toxicity and efficacy of accelerated radiotherapy with concurrent weekly cisplatin for locally advanced head and neck carcinoma. Head Neck. 2016;38(Suppl 1):E559–65. A retrospective review of 106 patients with LAHNC receiving CRT with weekly cisplatin (40mg/m2). This study reported acute toxicity data, as well as survival and disease-related outcomes, in addition to performing a sub-analysis of the oropharyngeal cohort based upon HPV status

  22. Gupta PK, Lal P, Bajpai R, et al. Long term results of comparison of concurrent low-dose daily cisplatin versus the standard weekly cisplatin with six fractions per week radiotherapy in locally advanced head neck cancer. South Asian J Cancer. 2016;5(2):80–4.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Levy A, Blanchard P, Bellefqih S, et al. Concurrent use of cisplatin or cetuximab with definitive radiotherapy for locally advanced head and neck squamous cell carcinomas. Strahlenther Onkol. 2014;190(9):823–31.

    Article  PubMed  Google Scholar 

  24. Rades D, Seidl D, Janssen S, et al. Chemoradiation of locally advanced squamous cell carcinoma of the head-and-neck (LASCCHN): is 20mg/m(2) cisplatin on five days every four weeks an alternative to 100mg/m(2) cisplatin every three weeks? Oral Oncol. 2016;59:67–72.

    Article  PubMed  Google Scholar 

  25. Sakashita T, Homma A, Hatakeyama H, et al. Clinical outcomes of weekly cisplatin chemoradiotherapy for patients with pyriform sinus cancer. Int J Clin Oncol. 2015;20(6):1081–5.

    Article  CAS  PubMed  Google Scholar 

  26. Shapiro LQ, Sherman EJ, Riaz N, et al. Efficacy of concurrent cetuximab vs. 5-fluorouracil/carboplatin or high-dose cisplatin with intensity-modulated radiation therapy (IMRT) for locally-advanced head and neck cancer (LAHNSCC). Oral Oncol. 2014;50(10):947–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Strom TJ, Trotti AM, Kish J, et al. Comparison of every 3 week cisplatin or weekly cetuximab with concurrent radiotherapy for locally advanced head and neck cancer. Oral Oncol. 2015;51(7):704–8.

    Article  CAS  PubMed  Google Scholar 

  28. Prestwich RJ, Sen M. Absent benefit of accelerated concomitant chemoradiotherapy. Lancet Oncol. 2012;13(4):e136. author reply e-7

    Article  PubMed  Google Scholar 

  29. Gillison ML, Koch WM, Capone RB, et al. Evidence for a causal association between human papillomavirus and a subset of head and neck cancers. J Natl Cancer Inst. 2000;92(9):709–20.

    Article  CAS  PubMed  Google Scholar 

  30. Chaturvedi AK, Engels EA, Pfeiffer RM, et al. Human papillomavirus and rising oropharyngeal cancer incidence in the United States. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2011;29(32):4294–301.

    Article  Google Scholar 

  31. Mehanna H, Beech T, Nicholson T, et al. Prevalence of human papillomavirus in oropharyngeal and nonoropharyngeal head and neck cancer—systematic review and meta-analysis of trends by time and region. Head Neck. 2013;35(5):747–55.

    Article  PubMed  Google Scholar 

  32. O’Sullivan B, Huang SH, Siu LL, et al. Deintensification candidate subgroups in human papillomavirus-related oropharyngeal cancer according to minimal risk of distant metastasis. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2013;31(5):543–50.

    Article  Google Scholar 

  33. O’Sullivan B, Huang SH, Perez-Ordonez B, et al. Outcomes of HPV-related oropharyngeal cancer patients treated by radiotherapy alone using altered fractionation. Radiother Oncol. 2012;103(1):49–56.

    Article  PubMed  Google Scholar 

  34. Lassen P, Primdahl H, Johansen J, et al. Impact of HPV-associated p16-expression on radiotherapy outcome in advanced oropharynx and non-oropharynx cancer. Radiother Oncol. 2014;113(3):310–6.

    Article  PubMed  Google Scholar 

  35. • Spreafico A, Huang SH, Xu W, et al. Impact of cisplatin dose intensity on human papillomavirus-related and -unrelated locally advanced head and neck squamous cell carcinoma. Eur J Cancer. 2016;67:174–82. A retrospective analysis examining the impact of cisplatin dose intensity when administered concurrently with radiotherapy in the treatment of HPV-positive and HPV-negative LAHNC patients. Results suggest cumulative cisplatin dose of >200mg/m2 is associated with survival benefit in HPV-negative LAHNC patients but not in HPV-positive patients with the exception of T4 or N3 subset where higher cumulative cisplatin dose was associated with a trend in improved OS

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Anna Spreafico MD, PhD.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

This article is part of the Topical Collection on Head and Neck Cancer

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Carlsson, L., Bratman, S.V., Siu, L.L. et al. The Cisplatin Total Dose and Concomitant Radiation in Locoregionally Advanced Head and Neck Cancer: Any Recent Evidence for Dose Efficacy?. Curr. Treat. Options in Oncol. 18, 39 (2017). https://doi.org/10.1007/s11864-017-0482-0

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11864-017-0482-0

Keywords

Navigation