Metronomic therapy irinotecan (IRI) capecitabine (CAP) plus bevacizumab (BEV) in treatment of advanced colorectal cancer (ACRC) in very elderly people.

Background: ACRC is one of most common neoplastic disease in very old pts. The administration of oral fluoropyrimidine (capecitabine-CAP) in a standard schedule of 1,200 mg/sqm twice a day for 14 d shows similar effects to 5-FU continuous infusion (C.I.). Furthermore, CAP- IRI showed super -additive antitumor activity. Recently many study show the safety and efficacy of a "flat dose" administration of CAP particularly in the treatment of elderly people with cancer. Also, the efficacy of BEV is well demonstrated in CRC pts. Aim of the study is to evaluate impact of bevacizumab (BEV) in combination with IRI and XEL in ACRC very old patients. Methods: 42 (20 f-22 m) elderly patients with advanced colorectal cancer (median age: 77; range: 73-91) were enrolled. Comprehensive Geriatric Assessment (CGA) was performed to assess eligibility for chemotherapy. All Patients were included into groups I, according to Balducci's classification of frailty. Primary endpoint: clinical response rates (RR) according to RECIST criteria and toxicity profile using NCI-CTC v2.0. Secondary endpoints: PFS, OS and QoL score measured through EORTC QLQ-C30 questionnaires. All patients were evaluated for common treatment-related adverse events with regard to haematological and liver toxicity, nausea and vomiting, stomatitis, diarrhea, hand/foot syndrome and sensory neuropathy, according to the ECOG Common Toxicity Criteria. Results: Patients were treated with IRI (180 mg/mq) + BEV (7.5 mg/Kg) on day 1q21, and XEL (fixed dose of 1,000 mg bid) assumed orally continuously for a maximum of 12 cycles. Medium value of cycles delivered was 9.7. Tumor response rates observed were 37.1% (CR+PR). Clinical benefit, including stable disease, was 77.8%. No grade 4 toxicity was experienced. QoL score improvement was noted in all pts after treatment. Median PFS was 12.3 months with a 6 months PFS rate of 82%. Median OS was 22 months with a 12 months survival probability of 77.8%. Conclusions: In elderly ACRC BEV plus IRI every 3 weeks with CAP continuously show a good toxicity and effectiveness profile and seem to be a valid terapeutical opportunity also for ACRC very old patients.