Concurrent use of vinorelbine and gefitinib induces supra-additive effect in head and neck squamous cell carcinoma cell lines
- 110 Downloads
Squamous cell carcinoma of the head and neck (HNSCC) remains a clinical challenge because of the high rate of locoregional disease recurrence. Standard treatment includes surgery, radiation, chemoradiation or a combination of these approaches. New therapies are needed to achieve improved survival, quality of life and organ function in these patients. A novel molecular targeted therapy incorporated into our current treatment strategies may have a significant role in the treatment of HNSCC. The aim of this study was to evaluate the sensitivity of HNSCC cell lines to vinorelbine combined with gefitinib in vitro.
Six recently established cell lines were used: UT-SCC-9, -11, -19A, -29 and -34 (laryngeal SCC) and UT-SCC-33 (oral cavity SCC). Chemosensitivity was tested using the 96-well plate clonogenic assay. The vinorelbine concentrations used varied between 0.4 and 1.0 nM and the gefitinib concentrations varied between 0.05 and 1.6 μM. Survival data were fitted to the LQ model, and the area under the curve (AUC) value was obtained with numerical integration. The type of interaction was determined by comparing the AUC ratio of the two drugs to the survival fraction (SF) of gefitinib alone.
In the current study the combination of vinorelbine and gefitinib had a clear supra-additive or additive cytotoxic effect on the HNSCC cell lines.
This finding is encouraging as a proof of the possible benefit of combing an EGFR targeting compound with a cell cycle specific drug and warrants further studies of available combinations in vitro.
KeywordsVinorelbine Gefitinib Iressa Head and neck squamous cell carcinoma
- Cohen MH, Williams GA, Sridhara R, Chen G, McGuinn WD, Morse D Jr, Abraham S, Rahman A, Liang C, Lostritto R, Baird A, Pazdur R (2004) Report from the FDA. United States food and drug administration drug approval summary: gefitinib (ZD1839; Iressa) tablets. Clin Cancer Res 10:1212–1218PubMedCrossRefGoogle Scholar
- Cooper JS, Pajak TF, Forastiere AA, Jacobs J, Campbell BH, Saxman SB, Kish JA, Kim HE, Cmelak AJ, Rotman M, Machtay M, Ensley JF, Chao KS, Schultz CJ, Lee N, Fu KK (2004) Radiation Therapy Oncology Group 9501/Intergroup. Postoperative concurrent radiotherapy and chemotherapy for high-risk squamous-cell carcinoma of the head and neck. N Engl J Med 6 350(19):1937–1944CrossRefGoogle Scholar
- Degardin M, Oliveira J, Geoffrois L, Rolland F, Armand JP, Bastit P, Chauvergne J, Fargeot P, van Glabbeke M, Lentz MA, Tresca P, Boudillet J, Fumoleau P, Cappelaere P (1998) An EORTC-ECSG phase II study of vinorelbine in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck. Ann Oncol 9(10):1103–1107PubMedCrossRefGoogle Scholar
- Erjala K, Sundvall M, Junttila TT, Zhang N, Savisalo M, Mali P, Kulmala J, Pulkkinen J, Grénman R, Elenius K (2006) Signaling via ErbB2 and ErbB3 associates with resistance and EGFR amplification with sensitivity to EGFR-inhibitor gefitinib in head and neck squamous cell carcinoma cells. Clin Cancer Res 12(13):4103–4111PubMedCrossRefGoogle Scholar
- Fukuoka M, Yano S, Giaccone G, Tamura T, Nakagawa K, Douillard J-Y,Nishiwaki Y, Vansteenkiste J, Kudoh S, Rischin D, Eek R, Horai T, Noda K, Takata I, Smit E, Averbuch S, Macleod A, Wolf M, Feyereislova A, Dong R-P, Baselga J (2003) A multi-institutional randomised phase II trial of ZD1839 for previously treated patients with advanced non-small-cell lung cancer (The IDEAL 1 Trial). J Clin Oncol 21(12):2237–2246PubMedCrossRefGoogle Scholar
- Garden AS, Harris J, Vokes EE, Forastiere AA, Ridge JA, Jones C, Horwitz EM, Glisson BS, Nabell L, Cooper JS, Demas W, Gore E (2004) Preliminary results of radiation therapy oncology group 97–03: a randomized phase II trial of concurrent radiation and chemotherapy for advanced squamous cell carcinomas of the head and neck. J Clin Oncol 15:22(14):2856–2864Google Scholar
- Gridelli C, Perrone F, Gallo C, De Marinis F, Ianniello G, Gigolari S, Cariello S, Di Costanzo F, D’Aprile M, Rossi A, Migliorino R, Bartolucci R, Bianco AR, Pergola M, Monfardini S (1997) Vinorelbine is well tolerated and active in the treatment of elderly patients with advanced non-small cell lung cancer. A two-stage phase II study. Eur J Cancer 33:392–397PubMedCrossRefGoogle Scholar
- Kies MS, Haraf DJ, Athanasiadis I, Kozloff M, Mittal B, Pelzer H, Rademaker AW, Wenig B, Weichselbaum RR, Vokes EE (1998) Induction chemotherapy followed by concurrent chemoradiation for advanced head and neck cancer: Improved disease control and survival. J Clin Oncol 16(8):2715–2721PubMedGoogle Scholar
- Kris MG, Natale RB, Herbst RS, Lynch TJ, Prager D, Belani CP, Schiller JH, Kelly K, Spiridonidis H, Sandler A, Albain KS, Cella D, Wolf MK, Averbuch SD, Ochs JJ, Kay AC (2003) Efficacy of gefitinib, an inhibitor of the epidermal growth factor receptor tyrosine kinase, in symptomatic patients with non-small cell lung cancer: a randomized trial. JAMA 290(16):2149–2158PubMedCrossRefGoogle Scholar
- Lansford CD, Grénman R, Bier H, Somers KD, Kim SY, Whiteside TL, Clayman GL, Welkoborsky H-J, Carey TE (1999) In: Masters JRW, Palsson B (eds) Human cell culture, vol. II, Chap. 28. Kluwer, Great Britain, pp 185–255Google Scholar
- LoRusso PM, Herbst RS, Rischin D, Ranson M, Calvert H, Raymond E, Kieback D, Kaye S, Gianni L, Harris A, Bjork T, Maddox AM, Rothenberg ML, Small EJ, Rubin EH, Feyereislova A, Heyes A, Averbuch SD, Ochs J, Baselga J (2003) Improvements in quality of life and disease-related symptoms in phase I trials of the selective oral epidermal growth factor receptor tyrosine kinase inhibitor ZD1839 in non-small cell lung cancer and other solid tumors. Clin Cancer Res 9(6):2040–2048PubMedGoogle Scholar
- Orecchia R, Jereczek-Fossa BA, Catalano G, Chiesa F, De Pas T, Masci G, Krengli M, Vavassori A, De Paoli F, Robertson G, Marrocco E, De Braud F (2002) Phase II trial of vinorelbine, cisplatin and continuous infusion of 5-fluorouracil followed by hyperfractionated radiotherapy in locally advanced head and neck cancer. Oncology 63:115–123PubMedCrossRefGoogle Scholar
- Pignon JP, Bourhis J, Domenge C, Designe L (2000) 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 18: 355(9208):949–955Google Scholar
- Ranson M, Hammond LA, Ferry D, Kris M, Tullo A, Murray PI, Miller V, Averbuch S, Ochs J, Morris C, Feyereislova A, Swaisland H, Rowinsky EK (2002) ZD1839, a selective oral epidermal growth factor receptor-tyrosine kinase inhibitor, is well tolerated and active in patients with solid, malignant tumors: results of a phase I trial. J Clin Oncol 20(9):2217–2219CrossRefGoogle Scholar
- Shintani S, Li C, Mihara M, Terakado N, Yano J, Nakashiro K, Hamakawa H (2003) Enhancement of tumor radioresponse by combined treatment with gefitinib (Iressa, ZD1839), an epidermal growth factor receptor tyrosine kinase inhibitor, is accompanied by inhibition of DNA damage repair and cell growth in oral cancer. Int J Cancer 107:1030–1037PubMedCrossRefGoogle Scholar
- Sunwoo JB, Herscher LL, Kroog GS, Thomas GR, Ondrey FG, Duffey DC, Solomon BI, Boss C, Albert PS, McCullugh L, Rudy S, Muir C, Zhai S, Figg WD, Cook JA, Mitchell JB, Van Waes C (2001) Concurrent paclitaxel and radiation in the treatment of locally advanced head and neck cancer. J Clin Oncol 19(3):800–811PubMedGoogle Scholar