Pre-emptive Cycline Treatment on Cetuximab-induced Skin Toxicity in Patients With Metastatic Colorectal Cancer Treated With an Intensified FOLFIRI.
Cetuximab, an Epidermal Growth Factor Receptor (EGFR) inhibitor, has shown to improve
FOLFIRI efficacy up to 59.3% OR, in wild KRAS patients with advanced colorectal cancer.
Skin toxicity occurs in 81.6% of patients as an acne-like skin rash developed on the face
and the trunk inducing pain, decreasing quality of life and drug compliance. Over 104
patients enrolled in a phase II clinical trial sponsored by Center Paul Papin (NCT 00
559741), a grade > or = 2 cetuximab-acneiform rash occured in 51 patients (49%). In this
trial Cetuximab was combined with a FOLFIRI intensified (5-FU intensification based on
pharmacokinetics and pharmacogenetic studies of UGT1A1 status and DPD). Until now, no
pre-emptive skin toxicity treatment with cycline has been demonstrated. Because of cycline's
anti inflammatory properties and their use in inflammatory acne, cycline could prevent
cetuximab-induced skin rash. In a randomized double-blind placebo-controlled phase III
trial, Jatoi et al., failed to highlight any cycline effect on 61 patients. On the other
hand, the STEPP study (95 pts) showed the impact of cycline to prevent panitumumab related
skin toxicities. Our primary objective is to reduce the incidence of grade > or = 2
acne-like skin rash by 30% with a 6 weeks pre-emptive cycline treatment in patients with
metastatic colorectal cancer undergoing cetuximab therapy.
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
reduction of Grade > or = 2 acne-like skin rash by 30%
Skin tolerance will be assessed by a dermatologist at each cycle and NCI CTCAE v4.0 will be use for grading. Skin standardized photographs will be done at every cycle and a central double blind review wil be planned. Time to first occurence of grade > or =2 skin toxicity will be assessed, and specificity.
6 weeks of pre-emptive cycline treatment
Olivier Capitain, MD, PhD
ICO Paul Papin
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)