Multifactorial pharmacogenetic analysis in colorectal cancer patients receiving 5-fluorouracil-based therapy together with cetuximab-irinotecan.

Aim: To examine the predictive value of gene polymorphisms potentially linked to toxicity, clinical response, time to progression and overall survival, following cetuximab-tegafur-uracil (UFT)-irinotecan therapy.

Methods: Fifty-two patients with advanced colorectal cancer were enrolled in an ancillary pharmacogenetic study of the phase II CETUFTIRI trial. Treatment consisted of 21 day cycles of cetuximab (day 1-day 8-day 15, 250 mg m(-2) week(-1) following a 400 mg m(-2) initial dose) together with irinotecan (day 1, 250 mg m(-2)) and UFT-folinic acid (days 1-14, 250 mg m(-2) day(-1) UFT, 90 mg day(-1) folinic acid).

Epidermal growth factor receptor protein detection in head and neck cancer patients: a many-faceted picture.

Purpose: Epidermal growth factor receptor (EGFR) overexpression is associated with poor prognosis in head and neck squamous cell carcinoma (HNSCC). Despite intensive biomarker studies, a consensual method for assessing EGFR protein expression is still lacking. Here we set out to compare three EGFR detection methods in tumor specimens from HNSCC patients.

Prospective analysis of the impact of VEGF-A gene polymorphisms on the pharmacodynamics of bevacizumab-based therapy in metastatic breast cancer patients.

What Is Already Known About This Subject: • Functional polymorphisms on the VEGF-A gene, known to be linked to cancer risk or to VEGF-A plasma concentrations, have been identified. So far, limited knowledge has been published on the relationships between toxicity/efficacy of bevacizumab-based therapy and VEGF-A polymorphisms (tumoral DNA). We therefore prospectively tested the impact of these five gene polymorphisms (blood DNA) on the pharmacodynamics of bevacizumab-based treatment administered in metastatic breast cancer patients.

Erlotinib in combination with capecitabine (5'dFUR) in resistant pancreatic cancer cell lines.

The combination of capecitabine and the tyrosine kinase inhibitor erlotinib has recently been tested in patients with gemcitabine-refractory pancreatic tumors, with limited success. To understand this lack of efficacy, we studied the molecular effects of these agents in Capan-1 and Capan-2 human pancreatic resistant cancer cells. Erlotinib up-regulated thymidine phosphorylase (+50%) and downregulated dihydropyrimidine dehydrogenase (+55%) in a cell-dependent manner, thus suggesting that the combination should result in synergism.

Methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and FOLFOX response in colorectal cancer patients.

What Is Already Known About This Subject: * Numerous clinical studies, including a few prospective ones, have reported conflicting results on the impact of gene polymorphisms related to fluorouracil (FU) and oxaliplatin pharmacodynamics.

What This Study Adds: * This prospective study is the first to report that clinical response to FOLFOX is significantly related to methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms (677C-->T and 1298A-->C), with a response rate of 37, 53, 63 and 80% in patients harbouring no, one, two or three favourable MTHFR alleles, respectively. * Only polymorphisms of genes related to oxaliplatin pharmacodynamics (GSTpi 105Ile-->Val and XPD 751Ly-->Gln) influenced progression-free survival.