Head and neck cancers are the commonest cancer in Southeast Asia. Despite being a surface cancer, it is associated with significant morbidity as despite early detection by the patients they often report for treatment late and hence are associated with poor prognosis. The role of neoadjuvant chemotherapy in head and neck cancer is still under evaluation; there is a large subgroup of population that does not respond to chemotherapy, and hence, most studies have failed to show any survival benefit. This study evaluated the role of neoadjuvant therapy with docetaxel and carboplatin in patients with oral cancer and correlated the response to human papilloma virus, EGFR1, EGFR2, and GADD45 expression.
A total of 24 locally advanced, non-metastatic oral cancer patients were included in the study. Tumor biopsies were taken prior to the start of neoadjuvant therapy for expression of EGFR, Her-2-Neu, and GADD45 by immunohistochemistry and for HPV by PCR. The response was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) criteria after three cycles of chemotherapy. Statistical analysis was performed using correlation and Kaplan–Meier analysis; the difference in survival was calculated with log rank test.
A total of 21 male and 3 female with a mean age of 53.12 years were enrolled. Sixty-five percent of these received three cycles of chemotherapy. Five patients were positive for HPV 16 and none for HPV 18. Twenty-two of 24 patients showed GADD45 expression, 3 showed expression of Her-2-Neu while all 24 showed expression for EGFR1 protein. Two-year overall survival was 81%; GADD45 expressions were found to significantly affect the overall and disease-free survival, while any of the other protein expression studied and HPV status was not significant.
The result of the present study shows significant downgrading of the oral cancers with neoadjuvant chemotherapy suggesting its utility in borderline operable cases. However, the response of chemotherapy does not appear to be related to the expression of EGFR, Her-2-Neu, and GADD45 protein or presence of HPV. Bone involvement, perineural invasion, and GADD45 expression significantly predict OS and DFS. All patients who did not express Gadd45 died before 2 years. Study with more subjects and longer follow-up should be carried out to elucidate this relation further.
Pignon JP, Bourhis J, Domenge C, Designé L. 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(9208):949-955.
Kumar A, Kumar M, Dixit R, Jaiswal R, Srivastava V, Pandey M. Presence of human papilloma virus and EGFR expression does not predict response to Neoadjuvant chemotherapy in oral cancer. World J Surg Med Radiat Oncol. 2012;1:103–10.
Li Y, Hong X, Hussain M, Sarkar SH, Li R, Sarkar FH. Gene expression profiling revealed novel molecular targets of docetaxel and estramustine combination treatment in prostate cancer cells. Mol Cancer Ther. 2005;4(3):389–98. PubMed
Xia W, Lau YK, Zhang HZ, Xiao FY, Johnston DA, Liu AR, Li L, Katz RL, Hung MC. Combination of EGFR, HER-2/neu, and HER-3 is a stronger predictor for the outcome of oral squamous cell carcinoma than any individual family members. Clin Cancer Res. 1999;5(12):4164–74. PubMed
Colevas AD, Norris CM, Tishler RB, Fried MP, Gomolin HI, Amrein P, Nixon A, Lamb C, Costello R, Barton J, Read R, Adak S, Posner MR. 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(11):3503–11. CrossRefPubMed
Posner MR, Glisson B, Frenette G, Al-Sarraf M, Colevas AD, Norris CM, Seroskie JD, Shin DM, Olivares R, Garay CA. 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(4):1096–104. CrossRefPubMed
Remenar E, Van Herpen C, Germa Lluch J, et al. A randomized phase III multicenter trial of neoadjuvant docetaxel plus cisplatin and 5-fluorouracil (TPF) versus neoadjuvant PF in patients with locally advanced unresectable squamous cell carcinoma of the head and neck (SCCHN). Final analysis of EORTC 24971. J Clin Oncol. 2006;24(Suppl 18):5516.
Vermorken JB, Remenar E, van Herpen C, Gorlia T, Mesia R, Degardin M, Stewart JS, Jelic S, Betka J, Preiss JH, van den Weyngaert D, Awada A, Cupissol D, Kienzer HR, Rey A, Desaunois I, Bernier J, Lefebvre JL; EORTC 24971/TAX 323 study group. Cisplatin, fluorouracil, and docetaxel in unresectable head and neck cancer. N Engl J Med 2007;357(17):1695-1704.
Albers AE, Grabow R, Qian X, Jumah MD, Hofmann VM, Krannich A, Pecher G. Efficacy and toxicity of docetaxel combination chemotherapy for advanced squamous cell cancer of the head and neck. Mol Clin Oncol. 2017;7(1):151–7. https://doi.org/10.3892/mco.2017.1281. Epub 2017 Jun 1 CrossRefPubMedPubMedCentral
Inhestern J, Schmalenberg H, Dietz A, Rotter N, Maschmeyer G, Jungehülsing M, Grosse-Thie C, Kuhnt T, Görner M, Sudhoff H, Wittekindt C, Guntinas-Lichius O. A two-arm multicenter phase II trial of one cycle chemoselection split-dose docetaxel, cisplatin and 5-fluorouracil (TPF) induction chemotherapy before two cycles of split TPF followed by curative surgery combined with postoperative radiotherapy in patients with locally advanced oral and oropharyngeal squamous cell cancer (TISOC-1). Ann Oncol. 2017;28(8):1917–22. https://doi.org/10.1093/annonc/mdx202. CrossRefPubMed
Hirakawa H, Hanai N, Suzuki H, Nishikawa D, Matayoshi S, Hasegawa Y, Suzuki M. Prognostic importance of pathological response to neoadjuvant chemotherapy followed by definitive surgery in advanced oral squamous cell carcinoma. Jpn J Clin Oncol. 2017;47(11):1038–46. https://doi.org/10.1093/jjco/hyx097. CrossRefPubMed
Kumar T, Kothari K, Patel MH, Ravi K, Yadav V. Surgical outcomes post neoadjuvant chemotherapy in stage IV cancers of oral cavity. Gulf J Oncolog. 2017;1(23):57–62.
Patil VM, Muttath G, Babu S, Kumar ST, Jones J, Sen S, Chakraborty S. Does the use of induction chemotherapy in oral cavity cancer compromise subsequent loco-regional treatment delivery: results from a matched pair analysis. Indian J Cancer. 2015;52(4):632–6. https://doi.org/10.4103/0019-509X.178442. CrossRefPubMed
Sadighi S, Keyhani A, Harirchi I, Garajei A, Aghili M, Kazemian A, Motiee Langroudi M, Zendehdel K, Nikparto N. Neoadjuvant chemotherapy for locally advanced squamous carcinoma of oral cavity: a pilot study. Acta Med Iran. 2015;53(6):380–6. PubMed
Colevas AD, Busse PM, Norris CM, Fried M, Tishler RB, Poulin M, Fabian RL, Fitzgerald TJ, Dreyfuss A, Peters ES, Adak S, Costello R, Barton JJ, Posner MR. 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(4):1331–9. CrossRefPubMed
Schrijvers D, Van Herpen C, Kerger J, Joosens E, Van Laer C, Awada A, Van den Weyngaert D, Nguyen H, Le Bouder C, Castelijns JA, Kaanders J, De Mulder P, Vermorken JB. 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(4):638–45. CrossRefPubMed
Tsukuda M, Mikami Y, Tanigaki Y, Katori H, Horiuchi C, Ikeda Y, Taguchi T, Ono M, Yoshida T, Sakuma Y, Aikoh K. Phase I trial of combined chemotherapy with docetaxel, cisplatin, and 5-fluorouracil for patients with locally advanced squamous cell carcinoma of the head and neck. Int J Clin Oncol. 2004;9(3):161–6. CrossRefPubMed
Umeda M, Komatsubara H, Ojima Y, Minamikawa T, Shigeta T, Shibuya Y, Yokoo S, Komori T. Lack of survival advantage in patients with advanced, resectable squamous cell carcinoma of the oral cavity receiving induction chemotherapy with cisplatin (CDDP), docetaxel (TXT) and 5-fluorouracil (5FU). Kobe J Med Sci. 2004;50(5–6):189–96. PubMed
- Effect of neoadjuvant chemotherapy and its correlation with HPV status, EGFR, Her-2-neu, and GADD45 expression in oral squamous cell carcinoma
Krishna Kiran Kannepali
- BioMed Central
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