Elevated Cyclin D1 Expression Is Predictive for a Benefit from TPF Induction Chemotherapy in Oral Squamous Cell Carcinoma Patients with Advanced Nodal Disease

Abstract

Induction chemotherapy is likely to be effective for biologically distinct subgroups of cancer patients with biomarker detection. In order to investigate the prognostic and predictive values of cyclin D1 expression in patients with oral squamous cell carcinoma(OSCC) who were treated in a prospective, randomized, phase 3 trial evaluating standard treatment with surgery and post-operative radiotherapy preceded or not by induction docetaxel, cisplatin and 5-fluorouracil(TPF). Immunohistochemical staining for cyclin D1 was performed in pretreatment biopsy specimens of 232 out of 256 clinical stage III/IVA OSCC patients randomized to the clinical trial. Cyclin D1 index was estimated as the proportion of tumor cells with cyclin D1 nuclear staining. A low cyclin D1 expression predicted significantly better overall survival(P=0.001), disease-free survival(P=0.005), locoregional recurrence-free survival(P=0.003) and distant metastasis-free survival(P=0.002) compared to high cyclin D1 expression. Cyclin D1 expression levels were not predictive of benefit from induction TPF in the population overall. However, patients with nodal stage cN2 whose tumors had high cyclin D1 expression treated with TPF had significantly greater overall survival(P=0.025) and distant metastasis-free survival(P=0.025) when compared to high cyclin D1 cN2 patients treated with surgery upfront. Patients with low cyclin D1 level or patients with cN0 or cN1 disease did not benefit from induction chemotherapy. This study indicates that cN2 OSCC patients with high cyclin D1 expression can benefit from the addition of TPF induction chemotherapy to standard treatment. Cyclin D1 expression could be used as a biomarker in further validation studies to select cN2 patients that could benefit from induction therapy.

The role of NLRP3 inflammasome in 5-fluorouracil resistance of oral squamous cell carcinoma

“…Docetaxel, cisplatin and 5-FU (TPF) induction chemotherapy was administered prior to surgery, and details of the therapeutic regimens had been previously described by Zhong et al [15]. Briefly, TPF induction chemotherapy consisted of docetaxel 75 mg/m 2 intravenously on day 1, followed by cisplatin 75 mg/m 2 intravenously on day 1, followed by 5-FU 750 mg/m 2 /day as a 120-h continuous intravenous infusion on days 1 through 5, every 3 weeks for 2 cycles.…”

The Significant Role of Cyclin D1 in the Synergistic Growth-inhibitory Effect of Combined Therapy of Vandetanib with 5-Fluorouracil for Gastric Cancer

“…It is possible in colorectal cancer that the expression of cyclin D1 is not an indicator of the chemosensitivity to 5-FU (55), but the synergistic effect of cyclin D1 with molecular-targeting drugs has not yet been demonstrated. However, chemosensitivity to 5-FU was predicted to be significantly better for patients with low expression of cyclin D1 in squamous cell carcinoma (56).…”

[18F]-FDG PET-CT prediction of response to induction chemotherapy in head and neck squamous cell carcinoma: Preliminary findings

“…In France, however, HPV infection is found in only 11.5-26% of cases of HNSCC [14]. ERCC1 gene expression and DPD (dihydropyrimidin dehydrogenase) cyclin D1 mutations [15,16] also offer interesting possibilities. There are, however, no validated biomolecular or genetic tests in current use.…”