Capecitabine and irinotecan with and without bevacizumab for advanced colorectal cancer patients

Abstract

Both regimens were well tolerated and offered effective tumor growth control in this outpatient setting. Severe gastrointestinal toxicities and thromboembolic events were rare and if observed were never fatal.

Irinotecan and Capecitabine (CAPIRI) Plus Bevacizumab in First-Line Treatment of Metastatic Colorectal Cancer

“…The efficacy results support the adequacy of the CAPIRI low dose regimen (irinotecan dose intensity of 80 mg/m 2 per week) in combination with bevacizumab with an ORR (63.3%), TTP (median 15 months) and OS (median 22.5 months) which are consistent with those reported in other studies with CAPIRI at low doses plus bevacizumab (Ardavanis et al, 2008;Moehler et al, 2009). Moreover, median OS observed in our study was among the range of OS rates (22.5-25.1 months) reported with FOLFIRI (irinotecan dose intensity of 90 mg/m 2 per week) regimen plus bevacizumab (Sobrero et al, 2009) or with bevacizumab plus other routine first-line chemotherapy regimens (Grothey et al, 2008;Van Cutsem et al, 2009).…”

“…Two international studies (BICC C and EORTC 40015) using high doses of irinotecan (250 mg/m 2 ) plus capecitabine (2000 mg/m 2 daily for 14 days) given 3-weekly (XELIRI) resulted in an unacceptable level of toxicity (Fuchs et al, 2008;Kohne et al, 2008). Later studies with CAPIRI at lower doses (capecitabine 800-1000 mg/m 2 twice a day for 14 days and irinotecan 200-240 mg/m 2 IV on day 1 every 3 weeks) (Cartwright et al, 2005;Kim et al, 2005;Park et al, 2004), obtained a therapeutic activity similar to that observed with FOLFIRI as well as an acceptable safety profile, particularly when bevacizumab was added to the regimen (Ardavanis et al, 2008;Moehler et al, 2009). In fact, doses as low as 800 mg/m 2 twice a day for capecitabine and 200 mg/m 2 for irinotecan have been proposed as a starting point for future trials based on the regional differences observed in a review of previous studies with capecitabine-irinotecan regimens (Cartwright et al, 2010).…”

Comparison of in vitro metabolic conversion of capecitabine to 5-FU in rats, mice, monkeys and humans - toxicological implications

“…Capecitabine alone or a regimen of capecitabine plus oxaliplatin (XELOX) is used for advanced or metastatic colorectal cancers (Van Cutsem et al, 2001;Cassidy et al, 2008) and the drug is also used as an adjuvant therapy for colorectal cancers. Recently the combination of bevacizumab, a recombinant humanized monoclonal antibody to the vascular endothelial growth factor VEGF, with capecitabine or XELOX is now considered to be a standard treatment for colorectal cancers (Fuchs et al, 2007;ReinacherSchick et al, 2008;Moehler et al, 2009).…”

Discovery of fruquintinib, a potent and highly selective small molecule inhibitor of VEGFR 1, 2, 3 tyrosine kinases for cancer therapy

“…Bevacizumab in combination with 5-fluorouracilbased chemotherapy has been approved as first/second line therapy for advanced colorectal cancer (CRC) and in combination with carboplatin and/or paclitaxel has been approved as first line therapy for advanced non-small cell lung cancer (NSCLC). [18][19][20][21] The success of bevacizumab can be attributed to its sustained target inhibition resulted from its long half-life and good safety profile due to its high specificity allowing it to combine with a variety of chemotherapies. However, bevacizumab has its limitations in the clinic, such as its intravenous dosing, immunogenicity and potential to induce autoimmune diseases after long term treatment.…”