In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 15_suppl ( 2019-05-20), p. 6040-6040
Kurzfassung:
6040 Background: A randomized phase 3 trial failed to demonstrate a survival advantage for TPF (docetaxel, cisplatin, and 5-fluorouracil) induction chemotherapy in the overall study population of patients with locally advanced and resectable oral squamous cell carcinoma (OSCC). It is possible that personalized TPF-based induction chemotherapy might improve outcomes in biomarker-defined subsets of patients. Methods: Immunohistochemical staining against stathmin was performed in pre-treatment biopsy specimens in 170 OSCC patients from our randomized trial. Chemoresistance to TPF chemotherapy drugs regulated by stathmin expression was investigated. The anti-cancer activity of TPF chemotherapy drugs alone, a combination of TPF drugs and PI3K-AKT-mTOR pathway inhibitors, and vincristine were investigated using in vitro and in vivo OSCC models. Results: OSCC patients with low stathmin expression benefited from TPF induction chemotherapy in terms of overall survival (HR = 0.102, 95% CI:0.013-0.781, P = 0.028), disease-free survival (HR = 0.070, 95% CI:0.009-0.525, P = 0.010), locoregional recurrence-free survival (HR = 0.070, 95% CI:0.009-0.524, P = 0.010), and distant metastasis-free survival (HR = 0.101, 95% CI:0.013-0.767, P = 0.027). Stathmin overexpression promoted cellular proliferation and chemoresistance to TPF drugs in OSCC (P 〈 0.05). PI3K pathway inhibitors decreased stathmin expression and phosphorylation, and improved the chemosensitivity to TPF drugs in vitro and in vivo (P 〈 0.05). Vincristine decreased stathmin expression and phosphorylation, and OSCC lines were significantly sensitive to vincristine in vitro and in vivo (P 〈 0.01). Conclusions: Our results suggest a potential personalized TPF induction chemotherapy on the basis of stathmin expression in OSCC patients: patients with low stathmin expression in the biopsy samples are suggested to receive TPF induction chemotherapy followed by surgical resection and post-operative radiotherapy. For patients with stathmin overexpression PI3K inhibitor is a good choice to improve the inductive effect of TPF chemotherapy drugs; vincristine is a potential alternative for a chemotherapy drug when a patient is chemoresistant to or unsuitable to receive TPF chemotherapy drugs; however, more clinical trials are warranted to verify this optimization protocol.
Materialart:
Online-Ressource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/JCO.2019.37.15_suppl.6040
Sprache:
Englisch
Verlag:
American Society of Clinical Oncology (ASCO)
Publikationsdatum:
2019
ZDB Id:
2005181-5
