Expression Levels of Thymidylate Synthase, Thymidylate Phosphorylase and Dihydropyrimidine Dehydrogenase in Head and Neck Squamous Cell Carcinoma: Preliminary Study

Introduction Pharyngo-laryngeal tumors classified as T3-4, N0-3, M0, are conventionally treated by mutilating surgery (total (pharyngo)-laryngectomy). Neo-adjuvant chemotherapy with 5-FU/platinum salt can be proposed in an attempt to preserve the larynx. The level of the response to chemotherapy ranges from 36 to 54% of cases. Thus, a large number of patients receive chemotherapy that is ineffective and not free from adverse effects. Three main enzymes are involved in the metabolism of 5-FU: thymidylate synthase (TS), thymidylate phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD). Several studies suggest that a high level of expression of these three genes correlates with a poor clinical response to 5-FU. The main purpose of our study was to look for a correlation between the levels of expression of the genes for sensitivity to 5-FU (TS, TP, DPD) within the tumor and the clinical response observed after three courses of chemotherapy combining 5-FU/platinum salt in patients presenting with advanced cancer of the pharyngolarynx. Methods This was a prospective genetic study that had required approval from the Ethics Committee. The main assessment criterion was based on the assessment of the clinical response by an ENT panendoscopy and a cervical CT scan, after three courses of chemotherapy. The expression of the genes was determined by quantitative RT-PCR, using total RNA extracted from tumor biopsies taken during the initial panendoscopy. Results The means calculated, in our study, for the three genes of interest (TS, TP, DPD) were lower in the responder group than those in the non-responder group. Discussion Our preliminary findings reveal trends that confirm the hypothesis that the lower the level of expression of the sensitivity genes, the better the clinical response to chemotherapy. They now form part of a larger study that is currently in progress

Very Long-Term Complete Remission Can Be Achieved in Men With High-Risk Localized Prostate Cancer and a Very High PSA Value: An Analysis of the GETUG 12 Phase 3 Trial.

Serum prostate specific antigen (PSA) is a well-known prognostic parameter in men with prostate cancer. The treatment of men with very high PSA values and apparently no detectable metastases is not fully established. Ancillary analysis from the GETUG 12 phase 3 trial. Patients with non-metastatic high-risk prostate cancer by bone and computerized tomography (CT) scan were randomly assigned to receive androgen deprivation therapy (ADT) and docetaxel plus estramustine or ADT alone. Relapse-free survival (RFS), clinical RFS, metastases-free survival (MFS), overall survival (OS), and prostate cancer-specific survival (PCSS) were estimated using the Kaplan-Meier method for different levels of PSA (50 ng/mL, 75 ng/mL, and 100 ng/mL). The relationship between PSA and outcomes was studied using residual-based approaches and spline functions. The median follow-up was 12 years (range: 0-15.3). Baseline PSA (<50 ng/mL, n = 328; ≥50ng/mL, n = 85) was associated with improved RFS (P = .0005), cRFS (P = .0024), and MFS (P = .0068). The 12-year RFS rate was 46.33% (CI 40.59-51.86), 33.59% (CI 22.55-44.97), and 11.76% (1.96-31.20) in men with PSA values <50 ng/mL (n = 328), 50-100 ng/mL (n = 68), and ≥100 ng/mL (n = 17), respectively. Exploratory analyses revealed no deviation from the linear relationship assumption between PSA and the log hazard of events. Men with apparently localized prostate cancer and a high baseline PSA value have a reasonable chance of being long-term disease-free when treated with curative intent combining systemic and local therapy