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ORIGINAL ARTICLE
Year : 2017  |  Volume : 13  |  Issue : 3  |  Page : 510-513

Docetaxel plus cisplatin plus fluorouracil versus carboplatin plus fluorouracil-cetuximab in first-line setting in patients with recurrent or metastatic head and neck squamous cell cancer who did not previously receive neoadjuvant or adjuvant chemotherapy, which is standard?


1 Department of Medical Oncology, Akdeniz University School of Medicine, Antalya, Turkey
2 Department of Antalya Research and Training Hospital, Antalya, Turkey

Date of Web Publication31-Aug-2017

Correspondence Address:
Hasan Mutlu
Akdeniz University School of Medicine, Department of Medical Oncology, Konyaaltı, Antalya
Turkey
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-1482.161933

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 > Abstract 


Background: The prognosis of recurrent or metastatic head and neck squamous cell cancer (HNSCC) is very poor. In the present retrospective study, we compared the impact of docetaxel plus cisplatin plus fluorouracil (TCF), and cisplatin plus fluorouracil plus cetuximab (CF-Ctx) regimens on the prognosis of patients with recurrent or metastatic HNSCC in first-line.
Materials and Methods: A total of 70 patients were evaluated as two groups, according to treatment protocol: TCF (n: 47) and CF-Ctx (n: 23). The groups were compared regarding survival.
Results: The median progression-free survival was 7.3 and 8.3 months, TCF and CF-Ctx groups, respectively, (P = 0.280). The median overall survival (OS) was 15.6 and 9.3 months for TCF and CF-Ctx groups, respectively, (P = 0.029). The dose reduction and using of granulocyte colony stimulating factor were significantly higher in TCF group (P = 0.048 and P = 0.018, respectively).
Conclusion: In first-line setting, TCF regimen is superior to CF-Ctx regimen in terms of OS in patients with recurrent or metastatic HNSCC, who did not previously receive neoadjuvant or adjuvant chemotherapy.

Keywords: Cetuximab, chemotherapy, first-line, head, and neck cancer, survival


How to cite this article:
Mutlu H, Salim DK, Gündüz &, Eryılmaz MK, Musri FY, Coşkun H&. Docetaxel plus cisplatin plus fluorouracil versus carboplatin plus fluorouracil-cetuximab in first-line setting in patients with recurrent or metastatic head and neck squamous cell cancer who did not previously receive neoadjuvant or adjuvant chemotherapy, which is standard?. J Can Res Ther 2017;13:510-3

How to cite this URL:
Mutlu H, Salim DK, Gündüz &, Eryılmaz MK, Musri FY, Coşkun H&. Docetaxel plus cisplatin plus fluorouracil versus carboplatin plus fluorouracil-cetuximab in first-line setting in patients with recurrent or metastatic head and neck squamous cell cancer who did not previously receive neoadjuvant or adjuvant chemotherapy, which is standard?. J Can Res Ther [serial online] 2017 [cited 2020 Jul 10];13:510-3. Available from: http://www.cancerjournal.net/text.asp?2017/13/3/510/161933




 > Introduction Top


Head and neck cancers are a heterogeneous group and have varying primary sites. Head and neck cancers are the 6th most common cancer, and the incidence of head and neck cancer is estimated to be more than 550,000 cases annually worldwide.[1] Most of head and neck cancer originate from a squamous cell line that cover the surfaces inside head and neck. In the presentation, approximately, 10% of head and neck squamous cell cancer (HNSCC) are metastatic setting while 60% of them are a locally advanced disease.[2] Unfortunately, most of the locally advanced HNSCC is associated with high rates local recurrence or distant metastasis after curative treatment. The 5-year overall survival (OS) patients with local, locally advanced, and metastatic diseases are 83%, 59%, and 36%, respectively.[3] Due to higher recurrence or distant metastasis rates, the chemotherapy regimens are the most important treatment modality that impact on prognosis in patients with recurrent or metastatic HNSCC.

Currently, platin based regimens are offered to improve survival or for palliation in these patients. Because of higher epidermal growth factor receptor (EGFR) expression in HNSCC, cetuximab, a monoclonal antibody targeting the EGFR, is commonly added to cisplatin-based regimens in the treatment of patients with HNSCC. In the phase III EXTREME trial, it was reported that cisplatin or carboplatin plus fluorouracil (CF) CF plus cetuximab (CF-Ctx) significantly prolonged progression-free survival (PFS), and OS compared with cisplatin or CF in patients with recurrent or metastatic HNSCC.[4] In previous studies, for the combinations of cisplatin plus fluorouracil plus taxan (docetaxel or paclitaxel), the median PFS and OS were reported between 4–10 and 6–13 months, respectively.[5],[6],[7],[8] Especially, the PFS and OS reached to 10 and 13 months by the combination of docetaxel plus cisplatin plus fluorouracil (TCF) regimens in patients with recurrent or metastatic HNSCC.[7],[8]

In the present study, we aimed to compare the efficacy of TCF and CF-Ctx chemotherapy regimens on the survival of patients who did not previously receive neoadjuvant or adjuvant chemotherapy with recurrent or metastatic HNSCC in first-line setting.


 > Materials and Methods Top


A total of 70 patients with recurrent or metastatic HNSCC from were analyzed retrospectively using hospital records between 2003 and 2015. When the patients, who had locally advanced disease at the diagnosis, have received prior neoadjuvant or adjuvant chemotherapy, they were not entered to the study. The patients were evaluated as two groups, according to a chemotherapy regimen in first-line setting: TCF (n: 47) and CF-Ctx (n: 23).

The age, sex, eastern cooperative oncology group performance status (ECOG PS), curative treatment protocol, which received for local disease at diagnosis, metastatic area at recurrence, dose reduction (yes or no), granulocyte colony-stimulating factor using (GCSF), and the using second-line chemotherapy were imported into the Statistical Package for the Social Sciences version 16.0 (SPSS 16.0, SPSS Inc., Chicago, IL, USA) from the medical archives retrospectively. In addition, the date of diagnosis (for patients with metastatic HNSCC, date of recurrence [for patients with recurrent HNSCC], time of progression, and date of death of patients with recurrent and metastatic HNSCC were imported into the SPSS 16.0 statistical program. PFS was defined as the time from the beginning of treatment to first progression. OS was defined as the time from the beginning of treatment to death.

Statistical analyses were performed using SPSS software version 16.0. To determine the properties of patients, frequency and mean analyses were performed. Comparisons of patient and tumor characteristics were performed using the Chi-square test and two independent samples t-test. The effect of combined treatment modality on PFS and OS of patients with metastatic or recurrent HNSCC was investigated using the log-rank test. Kaplan–Meier survival estimates were calculated. A P< 0.05 was considered significant.


 > Results Top


The properties of groups are shown in [Table 1]. The mean age was 61.6 ± 11.8 and 61 ± 9, 6 years for TCF and CF-Ctx groups, respectively (P = 0.842). There was not a significant difference between groups regarding sex and ECOG PS (P = 0.273 and P = 0.062, respectively). When evaluating groups, regarding primary tumor localization, a significant difference was not found between groups (P = 0.533). In both of groups, larynx cancer was the most common tumor area. The primary cancer of base of the tongue was higher in CF-Ctx group. The stage at diagnosis was similar (P = 0.554). The metastatic area at recurrence was not significantly differ between groups in patients with recurrent HNSCC (P = 0.593). Local or only lung recurrence was more in TCF group. Dose reduction was significantly more done in TCF group (29.8% vs 8.7% for TCF and CF-Ctx groups, respectively (P = 0.048). GCSF using was significantly higher in TCF group than CF-Ctx group (P = 0.018). The rates of second-line chemotherapy were 37% and 21.7% for TCF and CF-Ctx groups (P = 0.201).
Table 1: Properties or groups

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When we evaluated the groups in terms of PFS, median PFS was not significantly different between the groups (P = 0.280). The median PFS was 7.3 (95% confidence interval [CI] 4–10.5]) and 8.3 (95% CI 4.8–11.8) for TCF and CF-Ctx groups, respectively. PFS curves were shown in [Figure 1]. The median OS was significantly higher in the TCF group (P = 0.029). The median OS was 15.6 (95% CI 10.8–20.4) and 9.3 (95% CI 3.7–14.8) for TCF and CF-Ctx groups, respectively. OS curves were shown in [Figure 2].
Figure 1: Progression-free survival curves for the groups (P = 0.280)

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Figure 2: Overall survival curves for the groups (P = 0.029)

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 > Discussion Top


In the present study, we compared TCF and CF-Ctx regimens retrospectively in patients who did not previously receive neoadjuvant or adjuvant chemotherapy with recurrent or metastatic HNSCC. Our results revealed that the patients with recurrent or metastatic HNSCC, who did not previously receive neoadjuvant or adjuvant chemotherapy and were treated with TCF chemotherapy regimen, had significantly higher OS than the patients who treated with CF-Ctx regimen in first-line setting.

Randomized trials of taxan plus CF in HNSCC were generally designed in neoadjuvant setting.[9],[10],[11],[12] In studies included docetaxel, it was found that TPF was superior to CF regimen in terms of response rate and PFS or OS.[11],[12]

In previously, the incidence of EGFR expression was found as ≥95% in HNSCC.[13] Cetuximab has an inhibitory effect against EGFR, and it is used with radiotherapy in curative intent local or locally advanced HNSCC or in combination with chemotherapy in recurrent or metastatic HNSCC.[4],[14] In locally advanced HNSCC, cetuximab plus radiotherapy had significantly higher 5-year OS rates than radiotherapy.[14] Furthermore, in EXTREME trial, it was reported significantly higher OS results for CF-Ctx arm.[4]

When evaluated literature, it seems that there is not enough information regarding whether TCF or CF-CTx are not superior to each other. Any randomized trial aimed head to head comparison of TCF and CF-Ctx regimens in HNSCC cannot find. Especially, after EXTREME phase III trial, CF-Ctx regimen became the new standard regimen in the first-line treatment of patients with recurrent and/or metastatic HNSCC. However, according to our study results, TCF regimens were superior to CF-Ctx regimen in terms of survival. In previously conducted trials, they reported that docetaxel plus, cisplatin plus, cetuximab (TPEx) regimen had more promising data for OS in metastatic, or recurrent HNSCC and speculated that TPEx regimen is effective and might be a relevant substitute for PFEx as first-line treatment in fit patients with metastatic or recurrent HNSCC.[15],[16] In TREMPLIN study used TCF (induction) and cetuximab (concomitant with radiotherapy) as sequential in patients with locally advanced HNSCC who response to induction TCF more than 50%, the OS results were similar for radiotherapy plus cetuximab and radiotherapy plus cisplatin after induction TCF.[17]

In our study while PFS rates of groups were similar, there was a significant difference between OS rates of groups. Taxanes had significant antitumor activity, and taxane combinations had higher overall response rates compared nontaxane combinations in patients with locally advanced HNSCC.[18] The proportion of patients with multiorgan metastasis was nonsignificantly more in CF-Ctx group, and the rate of receiving second-line chemotherapy was nonsignificantly less in this group. The higher response rates may correct performance status of patients, and this may provide more receiving second-line chemotherapy. These factors may explain the difference between OS rates when PFS rates were similar in our study with a small population. HPV is positive in a significant proportion of HNSCC,[19] and it has known that HPV (+) HNSCC show significantly lower EGFR expression.[20] The response to the regimen with cetuximab may be poor in HNSCC with lower EGFR expression. In the first line, to use TPF regimen may eradicate HPV (+) tumor cells, and this may be disposed to the more responsive tumor to cetuximab based regimens in second-line. To determine HPV positivity may be important to explain survival difference in the presented study.

According to our results, TCF regimen is superior to CF-Ctx regimen in terms of OS in patients with recurrent or metastatic HNSCC. However, GCSF using and dose reduction were more in patients with HNSCC, who treated with TCF as similar literature information. The combined using of modified TCF and cetuximab as concurrent or sequential may be promising. The further studies are needed to determine the optimum treatment regimen in patients with recurrent or metastatic HNSCC.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 > References Top

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Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin 2011;61:69-90.  Back to cited text no. 1
    
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da Costa AA, D'Almeida Costa F, Ribeiro AR, Guimarães AP, Chinen LT, Lopes CA, et al. Low PTEN expression is associated with worse overall survival in head and neck squamous cell carcinoma patients treated with chemotherapy and cetuximab. Int J Clin Oncol 2015;20:282-9.  Back to cited text no. 2
    
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Janinis J, Papadakou M, Xidakis E, Boukis H, Poulis A, Panagos G, et al. Combination chemotherapy with docetaxel, cisplatin, and 5-fluorouracil in previously treated patients with advanced/recurrent head and neck cancer: A phase II feasibility study. Am J Clin Oncol 2000;23:128-31.  Back to cited text no. 7
    
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Pointreau Y, Garaud P, Chapet S, Sire C, Tuchais C, Tortochaux J, et al. Randomized trial of induction chemotherapy with cisplatin and 5-fluorouracil with or without docetaxel for larynx preservation. J Natl Cancer Inst 2009;101:498-506.  Back to cited text no. 10
    
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Vermorken JB, Remenar E, van Herpen C, Gorlia T, Mesia R, Degardin M, et al. Cisplatin, fluorouracil, and docetaxel in unresectable head and neck cancer. N Engl J Med 2007;357:1695-704.  Back to cited text no. 11
    
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Posner MR, Hershock DM, Blajman CR, Mickiewicz E, Winquist E, Gorbounova V, et al. Cisplatin and fluorouracil alone or with docetaxel in head and neck cancer. N Engl J Med 2007;357:1705-15.  Back to cited text no. 12
    
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Arteaga C. Targeting HER1/EGFR: A molecular approach to cancer therapy. Semin Oncol 2003;30 3 Suppl 7:3-14.  Back to cited text no. 13
    
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Bonner JA, Harari PM, Giralt J, Azarnia N, Shin DM, Cohen RB, et al. Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med 2006;354:567-78.  Back to cited text no. 14
    
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Even C, Bobillot B, Mayache-Badis L, Ferrand FR, Lezghed N, Bidault F, et al. Results of TPEx (docetaxel, cisplatin, cetuximab) regımen use ın fırst lıne patıents wıth recurrent/metastatıc squamous cell carcınoma of the head and neck ın a sıngle ınstıtutıon. Annals of Oncology 2014; 25 (suppl_4): iv340-iv356. 10.1093/annonc/mdu340.  Back to cited text no. 15
    
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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 multicentre, phase II GORTEC study. Ann Oncol. 2015 Jun 24. [Epub ahead of print].  Back to cited text no. 16
    
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Lefebvre JL, Pointreau Y, Rolland F, Alfonsi M, Baudoux A, Sire C, et al. Induction chemotherapy followed by either chemoradiotherapy or bioradiotherapy for larynx preservation: The TREMPLIN randomized phase II study. J Clin Oncol 2013;31:853-9.  Back to cited text no. 17
    
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Behera M, Owonikoko TK, Kim S, Chen Z, Higgins K, Ramalingam SS, et al. Concurrent therapy with taxane versus non-taxane containing regimens in locally advanced squamous cell carcinomas of the head and neck (SCCHN): A systematic review. Oral Oncol 2014;50:888-94.  Back to cited text no. 18
    
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Chung CH, Gillison ML. Human papillomavirus in head and neck cancer: Its role in pathogenesis and clinical implications. Clin Cancer Res 2009;15:6758-62.  Back to cited text no. 19
    
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