IRCC DOSING STUDIES

This document summarizes procedures for generating dosing studies at IRCC. More information can be found in Bertotti et al., 2011  .

Dosing and measuring drug response

For the assessment of tumor response to therapy, we used volume measurements and adopted a classification methodology loosely inspired by clinical criteria:

• Established tumors (average volume 400 mm3) from PDX mice (passages P3+) were treated with the following regimens: cetuximab (Merck) 20 mg/kg, twice-weekly or appropriate control.
• Tumor size was evaluated once-weekly by caliper measurements and the approximate volume of the mass was calculated using the formula 4/3π·(d/2)2·D/2, where d is the minor tumor axis and D is the major tumor axis.
• For the assessment of tumor response to therapy, we used volume measurements and adopted a classification methodology loosely inspired by clinical criteria:
  • Tumor regression (or shrinkage) was defined as a decrease of at least 50% in the volume of target lesions, taking as reference the baseline tumor volume;
  • At least a 35% increase in tumor volume identified disease progression
  • Responses that were neither sufficient reduction to qualify for shrinkage nor sufficient increase to qualify for progression were considered as disease stabilization.
• All animal procedures were approved by the Ethical Commission of the Institute for Cancer Research and Treatment and by the Italian Ministry of Health.