Serum Vascular Endothelial Growth Factor-A (VEGF-A) as a Biomarker in Squamous Cell Carcinoma of Head and Neck Patients Undergoing Chemoradiotherapy

Background: To evaluate serum VEGF-A levels in squamous cell carcinoma of head and neck (SCCHN)patients and relationships with response to therapy. Materials and Methods: Serum VEGF-A levels in patients(n=72) treated with radiotherapy (RT) or radio-chemotherapy (RCT) and controls (n=40) were measured byELISA. Results: Serum VEGF-A levels of the SCCHN cases were significantly higher (p=0.001) than in healthycontrols, and in patients with positive as compared to negative lymph node status (p=0.004). Similarly, patientswith advanced stage (Stage III-IV) disease had more greatly elevated levels of serum VEGF-A level than theirearly stage (Stage I-II) counterparts (p=0.001). In contrast, there was no significant difference (p=0.57) inserum level of VEGF-A in patients with advanced T-stage (T3-4) as compared to early stage (T1-2). Similarly,patients with distant metastasis had no significant (p=0.067) elevation in serum VEGF-A level as compared tonon-metastatic disease. However, the non-responder patients had significantly higher serum VEGF-A level ascompared to responders (p=0.001). Conclusions: Our results suggest that the serum VEGF-A level may be auseful biomarker for the prediction of response to therapy in SCCHN.     

Use of the folinic acid/5-fluorouracil/irinotecan (FOLFIRI 1) regimen in elderly patients as a first-line treatment for metastatic colorectal cancer: a Phase II study

Background  The aim of this study was to evaluate the effects of a combination of folinic acid, 5-fluorouracil (5FU) and irinotecan (FOLFIRI 1) administered every 2 weeks in a population of elderly subjects with advanced colorectal cancer. Patients and methods  Patients with metastatic colorectal cancer included in this study were aged at least 70 years, with a performance status of 0/1, without geriatric syndrome and without previous palliative chemotherapy. They received irinotecan [180 mg/m² intravenous (iv) infusion over 90 min] followed by folinic acid (400 mg/m² iv over 2 h), then 5FU (400 mg/m² iv bolus) and 5FU (2,400 mg/m² continuous iv infusion for 46 h) every 2 weeks. Results  Forty eligible patients were included. The median age was 77.3 years (range 70–84.7). The objective response rate was 40% and the stabilisation rate was 45%. Median progression-free survival was 8 months, overall survival was 17.2 months and cancer-related specific survival was 20.2 months. In total, 300 cycles of chemotherapy were administered with a median number of eight cycles per patient (range 1–18). Tolerance was good; grade 3/4 toxicities included diarrhoea (15%), asthenia (15%), nausea/vomiting (7.5%) and neutropenia (7.5%). One toxic death was observed due to grade 4 diarrhoea. Conclusion  The FOLFIRI 1 regimen is a valid therapeutic option for elderly patients in good clinical condition. This study was partly sponsored by Pfizer, Paris, France.     

Phase I clinical and pharmacokinetic study of E7070, a novel sulfonamide given as a 5-day continuous infusion repeated every 3 weeks in patients with solid tumours. A study by the EORTC Early Clinical Study Group (ECSG)

A single-agent dose-escalating phase I study on the novel sulfonamide E7070 was performed to determine the toxicity profile and the recommended dose for phase II studies. The pharmacokinetic profile of E7070 was also determined. E7070 was administered as a continuous infusion over 5 days repeated every 3 weeks. 27 patients were treated at doses ranging from 6 to 200 mg/m(2)/day. As with other administration schedules, the dose-limiting toxicities were dose-dependent, reversible neutropenia and thrombocytopenia. Although no objective responses were observed, seven patients had stable disease. E7070 displayed a non-linear pharmacokinetic profile, especially at dose-levels greater than 24 mg/m(2)/day, with a reduction in clearance and an increase in the half-life at the higher dose levels. The risk of myelosuppression became significant with an AUC greater than 4000 microg h/ml. The recommended dose of E7070 for further studies is 96 mg/m(2)/day when administered on a 5-day continuous infusion schedule every 3 weeks.