6 research outputs found
Outcomes of conjunctival compression sutures for hypotony after glaucoma filtering surgery
3openopenQuaranta L.; Riva I.; Floriani I.C:Quaranta, Luciano; Riva, Ivano; Floriani I., C
Outcomes of using a sutureless bovine pericardial patch graft for Ahmed glaucoma valve implantation
Twenty-four hour efficacy with preservative free tafluprost compared with latanoprost in patients with primary open angle glaucoma or ocular hypertension
10openopenKonstas A.G.; Quaranta L.; Katsanos A.; Riva I.; Tsai J.C.; Giannopoulos T.; Voudouragkaki I.C.; Paschalinou E.; Floriani I.; Haidich A.B.Konstas, A. G.; Quaranta, Luciano; Katsanos, A.; Riva, Ivano; Tsai, J. C.; Giannopoulos, T.; Voudouragkaki, I. C.; Paschalinou, E.; Floriani, I.; Haidich, A. B
Pharmacogenetic profiling for toxicity of oxaliplatin and fluoropyrimidines. Final report from an ancillary protocol to the TOSCA (Three Or Six Colon Adjuvant) trial
Aim
A number of germline polymorphisms have shown promising predictive role for chemotherapy related toxicity in colorectal cancer patients. However, large-scale validation trials are necessary before pharmacogenetic findings are incorporated into clinical practice. We investigated 17 polymorphisms in 11 genes for their association with toxicity of fluoropyrimidines and oxaliplatin (TS, MTHFR, ERCC1, XRCC1, XRCC3, XPD, GSTT, GSTP, GSTM, ABCC1, ABCC2) in colorectal cancer patients enrolled in a prospective randomized trial of adjuvant chemotherapy.
Methods
TOSCA is a non-profit, Italian, multicentre, randomized, non-inferiority phase III study conducted in high-risk stage II and stage III colorectal cancer patients treated with 6 or 3 months of either FOLFOX-4 or XELOX adjuvant chemoterapy. A planned sample of patients was accrued in the ancillary pharmacogenetic study. The primary endpoint was the evaluation of the relationship of genetic polymorphisms with occurrence of grade 3-4 CTCAE toxicity event (grade 2-4 for neurotoxicity).
Results
From July 2007 to October 2011, 531 patients were enrolled from 26 experimental centres (194 patients in 6-month FOLFOX-4 arm, 194 patients in 3-month FOLFOX-4 arm, 74 patients in 6-month XELOX arm, 69 patients in 3-month XELOX arm). Grade ≥3 neutropenia and grade >2 neurotoxicity events occurred in 150 (29%) and in 132 patients (24.8%), respectively. Diarrhea grade > 3 events occurred in 34 (6.5%) patients. None of the studied polymorphisms showed clinically relevant association with toxicity.
Conclusions
In the studied population, we ruled out a strong predictive role of known genetic variants for toxicity. Future investigations should address novel polymorphisms emerging from genome-wide association studies.
Disclosure
All authors have declared no conflicts of interest