Skip to main content
SpringerLink
Log in

Phase II study of docetaxel, cisplatin, and concurrent radiation followed by platinum-based adjuvant chemotherapy for technically unresectable, locally advanced head and neck squamous cell carcinoma

  • Original Article
  • Published:
International Journal of Clinical Oncology Aims and scope Submit manuscript

Abstract

Background

Phase I study of weekly administration of low-dose docetaxel/cisplatin concurrent with conventionally fractionated radiotherapy for locally advanced head and neck squamous cell carcinoma suggested the recommended dose of docetaxel at 10 mg/m2 and cisplatin at 20 mg/m2. Phase II study of the concurrent chemoradiotherapy for technically resectable disease showed satisfactory results.

Methods

This phase II study was designed to address efficacy and safety when patients with technically unresectable disease were treated with concurrent chemoradiotherapy, followed by two cycles of moderate-dose platinum-based adjuvant chemotherapy: docetaxel, cisplatin, and fluorouracil (modified TPF). Modified TPF was replaced with docetaxel/carboplatin when renal impairment became evident. Surgical salvage was considered when residual or recurrent locoregional disease was technically resectable and free of distant metastasis.

Results

Of 33 enrolled patients, 31 were analyzable: 24 (78 %) and 18 (58 %) patients completed chemoradiotherapy and adjuvant chemotherapy, respectively; 15 (48 %) patients completed study treatment per protocol, and overall complete response rate was 45 %. Seven patients underwent surgical salvage, which was successful in 4 patients. At a median follow-up of 60.8 months for surviving patients, median progression-free survival and median overall survival were 16.2 and 39.9 months, respectively. Grade 3 or 4 toxicity included mucositis (77 %) and dysphagia (45 %) during the chemoradiotherapy period and neutropenia (100 %) and febrile neutropenia (35 %) during the adjuvant period. No patient died of toxicity.

Conclusion

The tested regimen seems effective, although there is room for improvement in adjuvant chemotherapy because of the high toxicity and low compliance of modified TPF.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Vermorken JB, Remenar E, van Herpen C et al (2007) Cisplatin, fluorouracil, and docetaxel in unresectable head and neck cancer. N Engl J Med 357:1695–1704

    Article  CAS  PubMed  Google Scholar 

  2. Adelstein DJ, Li Y, Adams GL et al (2003) 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 21:92–98

    Article  PubMed  Google Scholar 

  3. Hitt R, Grau JJ, López-Pousa A et al (2014) A randomized phase III trial comparing induction chemotherapy followed by chemoradiotherapy versus chemoradiotherapy alone as treatment of unresectable head and neck cancer. Ann Oncol 25:216–225

    Article  CAS  PubMed  Google Scholar 

  4. Machtay M, Moughan J, Trotti A et al (2008) Factors associated with severe late toxicity after concurrent chemoradiation for locally advanced head and neck cancer: an RTOG analysis. J Clin Oncol 26:3582–3589

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Inohara H, Inoue T, Akahani S et al (2004) Concurrent chemoradiotherapy with cisplatin and docetaxel for advanced head and neck cancer. A phase I study. Anticancer Res 24:4135–4140

    CAS  PubMed  Google Scholar 

  6. Inohara H, Takenaka Y, Yoshii T et al (2015) Phase II study of docetaxel, cisplatin, and concurrent radiation for technically resectable stage III–IV squamous cell carcinoma of the head and neck. Int J Radiat Oncol Biol Phys 91:934–941

    Article  CAS  PubMed  Google Scholar 

  7. Maruyama H, Yasui T, Ishikawa-Fujiwara T et al (2014) Human papillomavirus and p53 mutations in head and neck squamous cell carcinoma among Japanese population. Cancer Sci 105:409–417

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Therasse P, Arbuck SG, Eisenhauer EA et al (2000) New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 92:205–216

    Article  CAS  PubMed  Google Scholar 

  9. Johnson FM, Garden A, Palmer JL et al (2004) A phase II study of docetaxel and carboplatin as neoadjuvant therapy for nasopharyngeal carcinoma with early T status and advanced N status. Cancer (Phila) 100:991–998

    Article  CAS  Google Scholar 

  10. Benasso M, Bonelli L, Numico G et al (1997) Treatment with cisplatin and fluorouracil alternating with radiation favourably affects prognosis of inoperable squamous cell carcinoma of the head and neck: results of a multivariate analysis on 273 patients. Ann Oncol 8:773–779

    Article  CAS  PubMed  Google Scholar 

  11. Poeta ML, Manola J, Goldwasser MA et al (2007) TP53 mutations and survival in squamous-cell carcinoma of the head and neck. N Engl J Med 357:2552–2561

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Allen CT, Lewis JS, El-Mofty SK et al (2010) Human papillomavirus and oropharynx cancer: biology, detection and clinical implications. Laryngoscope 120:1756–1772

    Article  PubMed  Google Scholar 

  13. Chaturvedi AK, Engels EA, Pfeiffer RM et al (2011) Human papillomavirus and rising oropharyngeal cancer incidence in the United States. J Clin Oncol 29:4294–4301

    Article  PubMed  PubMed Central  Google Scholar 

  14. Näsman A, Attner P, Hammarstedt L et al (2009) Incidence of human papillomavirus (HPV) positive tonsillar carcinoma in Stockholm, Sweden: an epidemic of viral-induced carcinoma? Int J Cancer 125:362–366

    Article  PubMed  Google Scholar 

  15. Nakashima T, Sugasawa M, Sakihama N et al (2014) Prevalence of human papillomavirus in oropharyngeal cancer: a multicenter study in Japan. Oncology 87:173–182

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Otorhinolaryngology-Head and Neck Surgery, Osaka University School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan

    Susumu Nakahara, Yukinori Takenaka, Suetaka Nishiike, Yoshifumi Yamamoto, Tadashi Yoshii, Yoichiro Tomiyama & Hidenori Inohara

  2. Department of Radiation Oncology, Osaka University School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan

    Kazuhiko Ogawa, Yuji Seo, Fumiaki Isohashi, Osamu Suzuki, Yasuo Yoshioka & Iori Sumida

Authors
  1. Susumu Nakahara
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yukinori Takenaka
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kazuhiko Ogawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Suetaka Nishiike
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yoshifumi Yamamoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yuji Seo
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Fumiaki Isohashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Osamu Suzuki
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Yasuo Yoshioka
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Iori Sumida
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Tadashi Yoshii
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Yoichiro Tomiyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Hidenori Inohara
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hidenori Inohara.

Ethics declarations

Conflict of interest

Hidenori Inohara received a research grant from SANOFI.

Electronic supplementary material

Below is the link to the electronic supplementary material.

10147_2016_997_MOESM1_ESM.pdf

Online Resource 1. Computed tomography (CT) images of patient with cT3N3 HPV16-positive oropharynx cancer. Local disease showed complete response (CR) to study treatment; regional disease showed partial response (PR); residual disease was surgically excised by neck dissection. Local recurrence became evident 6 months after the completion of study treatment and was surgically excised. The defect was repaired with a free rectus abdominis musculocutaneous flap. The patient stayed free of disease after the late salvage surgery. a Baseline. Note the internal carotid artery (ICA) sandwiched between primary tumor and metastatic node. The metastatic node was firmly fixed to the neck. b After study treatment. c After early salvage surgery for residual neck disease. d After late salvage surgery for local recurrence (PDF 110 kb)

10147_2016_997_MOESM2_ESM.pdf

Online Resource 2. CT images of patient with cT2N2b HPV16-positive oropharynx cancer. Although local disease showed CR and preexisting regional disease shrank after study treatment, a new regional lesion appeared during study treatment. Regional response was assessed as progressive disease, and the regional disease was surgically excised by extended neck dissection. Nodal recurrence and skin metastasis became evident 8 months after the completion of study treatment, and the patient died of the disease. a Baseline. Note ICA sandwiched between primary tumor and metastatic node, and metastatic node invading into prevertebral lamina of cervical fascia. Metastatic node was firmly fixed to the neck. b After study treatment. c After early salvage surgery for neck disease. Note recurrent lesion (arrow) in the posterior region of the neck (PDF 115 kb)

10147_2016_997_MOESM3_ESM.pdf

Online Resource 3. CT images of patient with cT4aN2c hypopharynx cancer. Both local and regional disease showed PR to study treatment. The patient underwent total paryngolaryngectomy plus neck dissection, and the defect was repaired with a free jejunum graft. The patient stayed free of disease after the early salvage surgery. a Baseline. Note multiple nodal metastases as well as retropharyngeal node adherent to ICA. b After study treatment. Note local residual disease (PDF 110 kb)

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Nakahara, S., Takenaka, Y., Ogawa, K. et al. Phase II study of docetaxel, cisplatin, and concurrent radiation followed by platinum-based adjuvant chemotherapy for technically unresectable, locally advanced head and neck squamous cell carcinoma. Int J Clin Oncol 21, 1030–1037 (2016). https://doi.org/10.1007/s10147-016-0997-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10147-016-0997-6

Keywords

Search

Navigation