Abstract
Background
Standard treatment for recurrent/metastatic head and neck squamous cell carcinoma (RM-SCCHN) is based in on platinum and cetuximab combination therapy. Unfortunately, not all patients are candidates to receive platinum-based treatment, because of different conditions as comorbidity and poor performance status. Weekly paclitaxel and cetuximab (WPC) is an active therapeutic alternative, based on a phase II study, with less toxicity. Our main objective is to confirm its activity in unselected patients, mostly unfit for aggressive therapies, analysing also some clinically relevant prognostic factors (PFs).
Methods
Retrospective data was collected for RM-SCCHN patients, treated at our institution between January 2008 and July 2014 with weekly paclitaxel (80 mg/m2) and cetuximab (400/250 mg/m2).
Results
148 patients were treated. The objective response rate (OR) was as follows: 13 patients (8.78%) complete response (CR); 57 patients (38.51%) partial response (PR) and 30 patients (20.3%) stable disease (SD). Median overall survival (OS) was 10 months (95% CI 8.31–11.69) and median progression free survival (PFS) was 7 months (95% CI 5.88–8.12). Response to treatment showed independent prognosis relevance as PF in multivariate analysis for PFS and OS. Furthermore, decline in serum magnesium during the treatment was also an independent PF for OS.
Conclusions
WPC activity was confirmed as a useful therapy on real-life unselected RM-SCCHN patients, with similar benefit to that obtained in the phase II study, and comparable to platinum and cetuximab based treatment, confirming its value in unfit patients. In addition to treatment response, a change in serum magnesium values during treatment was proved as independent PF on OS.
Similar content being viewed by others
References
Argiris A, Karamouzis MV, Raben D, Ferris RL. Head and neck cancer. Lancet. 2008;371(9625):1695–709.
Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010;127(12):2893–917.
Brockstein B, Haraf DJ, Rademaker AW, Kies MS, Stenson KM, Rosen F, et al. Patterns of failure, prognostic factors and survival in locoregionally advanced head and neck cancer treated with concomitant chemoradiotherapy: a 9-year, 337-patient, multi institutional experience. Ann Oncol. 2004;15(8):1179–86.
Marur S, Forastiere AA. Head and neck cancer: changing epidemiology, diagnosis, and treatment. Mayo Clin Proc. 2008;83(4):489–501.
Winquist E, Al-Rasheedy I, Nichols AC, Palma DA, Stitt L. Temporal changes in the efficacy of chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck: a systematic review and meta-analysis. Cancer Treat Rev. 2014;40(9):1073–9.
Vermorken JB, Mesia R, Rivera F, Remenar E, Kawecki A, Rottey S, et al. Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med. 2008;359(11):1116–27.
Grau JJ, Caballero M, Verger E, Monzó M, Blanch JL. Weekly paclitaxel for platin-resistant stage IV head and neck cancer patients. Acta Otolaryngol. 2009;129(11):1294–9.
Fayette J, Montella A, Chabaud S, Bachelot T, Pommier P, Girodet D, et al. Paclitaxel is effective in relapsed head and neck squamous cell carcinoma: a retrospective study of 66 patients at a single institution. Anticancer Drugs. 2010;21(5):553–8.
Lynch TJ, Patel T, Dreisbach L, McCleod M, Heim WJ, Hermann RC, et al. Cetuximabandfirst-line taxane/carboplatin chemotherapy in advanced non-small-cell lung cancer: results of the randomized multicenter phase III trial BMS099. J Clin Oncol. 2010;28(6):911–7.
Modi S, D’Andrea G, Norton L, Yao TJ, Caravelli J, Rosen PP, et al. A phase I study of cetuximab/paclitaxel in patients with advanced-stage breast cancer. Clin Breast Cancer. 2006;7(3):270–7.
Hitt R, Irigoyen A, Cortes-Funes H, Grau JJ, García-Sáenz JA, Cruz Hernandez JJ, Spanish Head and Neck Cancer Cooperative Group (TTCC). Phase II study of the combination of cetuximab and weekly paclitaxel in the first-line treatment of patients with recurrent and/or metastatic squamous cell carcinoma of head and neck. Ann Oncol. 2012;23(4):1016–22.
Stell PM, Morton RP, Campbell IT, Wilson JA. Survival after “palliative” cytotoxic chemotherapy for head-and-neck cancer. Lancet. 1983;2(8360):1205.
Corrêa GT, Bandeira GA, Cavalcanti BG, Santos FB, Rodrigues Neto JF, Guimarães AL, et al. Analysis of ECOG performance status in head and neck squamous cell carcinoma patients: association with sociodemographical and clinical factors, and overall survival. Support Care Cancer. 2012;20(11):2679–85.
Wang JR, Habbous S, Espin-Garcia O, Chen D, Huang SH, Simpson C, et al. Comorbidity and performance status as independent prognostic factors in patients with head and neck squamous cell carcinoma. Head Neck. 2016;38(5):736–42.
Cojocariu OM, Huguet F, Lefevre M, Périé S. Prognosis and predictive factors in head-and-neck cancers. Bull Cancer. 2009;96(4):369–78.
Weinberger PM, Yu Z, Haffty BG, Kowalski D, Harigopal M, Brandsma J, et al. Molecular classification identifies a subset of human papillomavirus–associated oropharyngeal cancers with favorable prognosis. J Clin Oncol. 2006;24(5):736–47.
Piccirillo JF, Tierney RM, Costas I, Grove L, Spitznagel Jr EL. Prognostic importance of comorbidity in a hospital-based cancer registry. JAMA. 2004;291(20):2441–7.
Kallogjeri D, Piccirillo JF, Spitznagel Jr EL, Steyerberg EW. Comparison of scoring methods for ACE-27: simpler is better. J Geriatr Oncol. 2012;3(3):238–45.
Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40(5):373–83.
Bogaerts J, Ford R, Sargent D, Schwartz LH, Rubinstein L, Lacombe D, RECIST Working Party, et al. Individual patient data analysis to assess modifications to the RECIST criteria. Eur J Cancer. 2009;45(2):248–60.
Nin RM, Borgoñón MP, Cruz Hernández JJ, Casado DI, SEOM(Spanish Society for Medical Oncology). SEOM clinical guidelines for the treatment of head and neck cancer. Clin Transl Oncol. 2010;12(11):742–8.
Sacco AG, Cohen EE. Current treatment options for recurrent or metastatic head and neck squamous cell carcinoma. J Clin Oncol. 2015;33(29):3305–13.
Guigay J, Fayette J, Dillies AF, Sire C, Kerger JN, Tennevet I, et al. Cetuximab, docetaxel, and cisplatin as first-line treatment in patients with recurrent or metastatic head and neck squamous cell carcinoma: a multicenter, phase II GORTEC study. Ann Oncol. 2015;26(9):1941–7.
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 ClinOncol. 2005; 23(34): 8646-54. Erratum in: J ClinOncol. 2006 Feb 1; 24(4): 724.
Baselga J, Trigo JM, Bourhis J, Tortochaux J, Cortés-Funes H, Hitt R, et al. Phase II multicenter study of the antiepidermal growth factor receptor monoclonal antibody cetuximab in combination with platinum-based chemotherapy in patients with platinum-refractory metastatic and/or recurrent squamous cell carcinoma of the head and neck. J Clin Oncol. 2005;23(24):5568–77.
Vermorken JB, Trigo J, Hitt R, Koralewski P, Diaz-Rubio E, Rolland F, et al. Open-label, uncontrolled, multicenter phase II study to evaluate the efficacy and toxicity of cetuximab as a single agent inpatients with recurrent and/or metastatic squamous cell carcinoma of the head and neck who failed to respond to platinum-based therapy. J Clin Oncol. 2007;25(16):2171–7.
Péron J, Ceruse P, Lavergne E, Buiret G, Pham BN, Chabaud S, et al. Paclitaxel and cetuximab combination efficiency after the failure of a platinum-based chemotherapy in recurrent/metastatic head and neck squamous cell carcinoma. Anticancer Drugs. 2012;23(9):996–1001.
Jiménez B, Trigo JM, Pajares BI, Sáez MI, Quero C, Navarro V, et al. Efficacy and safety of weekly paclitaxel combined with cetuximab in the treatment of pretreated recurrent/metastatic head and neck cancer patients. Oral Oncol. 2013;49(2):182–5.
Sosa AE, Grau JJ, Feliz L, Pereira V, Alcaraz D, Muñoz-García C, et al. Outcome of patients treated with palliative weekly paclitaxel plus cetuximab in recurrent head and neck cancer after failure of platinum-based therapy. Eur Arch Otorhinolaryngol. 2014;271(2):373–8.
Wang Q, Qi Y, Zhang D, Gong C, Yao A, Xiao Y, et al. Electrolyte disorders assessment in solid tumor patients treated with anti-EGFR monoclonal antibodies: a pooled analysis of 25 randomized clinical trials. Tumour Biol. 2015;36(5):3471–82.
Shechter M. Magnesium and cardiovascular system. Magnes Res. 2010;23(2):60–72.
Vincenzi B, Galluzzo S, Santini D, Rocci L, Loupakis F, Correale P, et al. Early magnesium modifications as a surrogate marker of efficacy of cetuximab-based anticancer treatment in KRAS wild-type advanced colorectal cancer patients. Ann Oncol. 2011;22(5):1141–6.
Vickers MM, Karapetis CS, Tu D, O’Callaghan CJ, Price TJ, Tebbutt NC, et al. Association of hypomagnesemia with inferior survival in a phase III, randomized study of cetuximab plus best supportive care versus best supportive care alone: NCIC CTG/AGITG CO. 17. Ann Oncol. 2013;24(4):953–60.
Abdel-Rahman O, Fouad M. Correlation of cetuximab-induced skin rash and outcomes of solid tumor patients treated with cetuximab: A systematic review and meta-analysis. Crit Rev Oncol Hematol. 2015;93(2):127–35.
Bar-Ad V, Zhang QE, Harari PM, Axelrod R, Rosenthal DI, Trotti A, et al. Correlation between the severity of cetuximab-induced skin rash and clinical outcome for head and neck cancer patients: the RTOG experience. Int J Radiat Oncol Biol Phys. 2016;95(5):1346–54. doi:10.1016/j.ijrobp.2016.03.011.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
The study was assessed and approved by the Aragon clinical research ethics committee (CEICA) in Spain.
Conflict of interest
Isabel Pajares Bernad: no conflicts of interest. Javier Martínez Trufero: no conflicts of interest. Lourdes Calera Urquizu: no conflicts of interest. Roberto A. Pazo Cid: no conflicts of interest. Ana Cebollero de Miguel: no conflicts of interest. María J. Agustín: no conflicts of interest. Manuela Lanzuela: no conflicts of interest. Antonio Antón: no conflicts of interest.
Research involving human participants and/or animals
This article does not contain any studies with human participants or animals performed by any of the authors.
Informed consent
Not necessary.
Additional information
I. Pajares Bernad and J. Martínez Trufero active members of TTCC (Spanish Group of Research in Head and Neck Cancer).
Rights and permissions
About this article
Cite this article
Bernad, I.P., Trufero, J.M., Urquizu, L.C. et al. Activity of weekly paclitaxel−cetuximab chemotherapy in unselected patients with recurrent/metastatic head and neck squamous cell carcinoma: prognostic factors. Clin Transl Oncol 19, 769–776 (2017). https://doi.org/10.1007/s12094-016-1604-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12094-016-1604-z