In this study, researchers from France investigated the efficacy and safety of single-agent, high-dose irinotecan 500 mg/m2 as first-line treatment for advanced colorectal cancer (CRC).
The team examined a first cycle of therapy with irinotecan at a dose of 350 mg/m2 every 3 weeks; this could be escalated to 500 mg/m2 for second and subsequent cycles depending on toxicity.
They determined efficacy, safety, and pharmacokinetics in the intent to treat (ITT) population and high-dose population.
The high-dose population consisted of patients who had received at least three cycles of irinotecan, the second and third at 500 mg/m2.
|Response rates for intent to treat and the high-dose populations were 25% and 36%, respectively.|
|Cancer Chemotherapy and Pharmacology|
The research team found that off 49 patients enrolled into the study (ITT population), 63% received at least 2 cycles of treatment with cycles 2 and 3 at an irinotecan dose of 500 mg/m2.
The team found response rates for the ITT and the high-dose populations were 25% and 36%, respectively.
The team identified the main grade 3/4 toxicities per cycle in the ITT and high-dose populations were neutropenia 22% and 17%, febrile neutropenia 5% and 3%, and diarrhoea 12% and 7%, respectively.
In addition, the pharmacokinetics of irinotecan and its metabolite SN-38 were investigated in 31 patients in cycle 1 and 22 patients in cycle 2.
The researchers determined that irinotecan clearance and SN-38 exposure were not sufficiently correlated with toxicity in cycle 1, to identify patients for dose increase in subsequent cycles.
Furthermore, the exposure to irinotecan and SN-38 increased in proportion to dose from 350 to 500 mg/m2.
Dr Ychou's team concluded, "These results suggest that high-dose irinotecan can be safely administered as first-line monotherapy to approximately two-thirds of patients who present with advanced CRC following a selective first cycle".