Capecitabine Plus 3-Weekly Irinotecan (XELIRI Regimen) as First-Line Chemotherapy for Metastatic Colorectal Cancer

Patt, Yehuda Z.; Lee, Fa Chyi; Liebmann, James; Diamandidis, D.; Eckhardt, S. Gail; Javle, Milind; Justice, Glen; Keiser, W.; Salvatore, Joseph R.; Bexon, Alice; Lin, Edward H.

doi:10.1097/coc.0b013e31804b40bb

Cited by 50 publications

(61 citation statements)

References 39 publications

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“…Although a comparison of results from different phase II studies can be only speculative, the efficacy of our schedule is in line with that obtained by the other groups who have also published response data in phase II trials testing capecitabine -irinotecan combination regimens (Bajetta et al, 2004;Park et al, 2004;Borner et al, 2005;Cartwright et al, 2005;Kim et al, 2005;Rea et al, 2005;Patt et al, 2007;Choi et al, 2008) (Table 3). Indeed, our median TTP and OS are among the highest of those published to date with this combination.…”

Section: Discussionsupporting

confidence: 75%

“…In Table 3, which summarises the main grade 3 -4 toxicities per patient reported in previous phase II studies testing the combination of capecitabine and irinotecan, the improved tolerability of the 2-weekly regimen is notable: grade 3 -4 neutropenia and diarrhoea ranged between 5 -28 and 8 -34% in other phase II studies, respectively, compared with respective rates of 6 and 15% in this study. Unlike the current study, grade 3 -4 hand -foot syndrome was reported in most of those studies (Cartwright et al, 2005;Patt et al, 2007;Choi et al, 2008). Our regimen also appears to be associated with a lower rate of grade 3 -4 neutropenia (6 vs 24 -23%) and a similar rate of grade 3 -4 diarrhoea (15 vs 14 -11%) compared with FOLFIRI (Tournigand et al, 2004;Van Cutsem et al, 2007).…”

Section: Discussioncontrasting

confidence: 48%

“…This approach has also been used successfully with the XELIRI regimen in patients with other known risk factors, for example, renal impairment, previous pelvic irradiation, and older age (Patt et al, 2007;Van Cutsem et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

“…Following these results, several investigators tested the combination of irinotecan with capecitabine in an attempt to improve on the available 5-FU/LV-based regimens. Encouraging efficacy results from phase II studies were reported with combination regimens of capecitabine and irinotecan given weekly, on days 1 and 8 (CAPIRI) or 3-weekly (XELIRI) as first-line treatment for MCRC (Bajetta et al, 2004;Park et al, 2004;Borner et al, 2005;Cartwright et al, 2005;Kim et al, 2005;Rea et al, 2005;Patt et al, 2007). However, dose reductions of both drugs were necessary in most studies to improve the safety profile of these regimens.…”

mentioning

confidence: 99%

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Capecitabine in combination with irinotecan (XELIRI), administered as a 2-weekly schedule, as first-line chemotherapy for patients with metastatic colorectal cancer: a phase II study of the Spanish GOTI group

et al. 2009

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BACKGROUND: Combination chemotherapy is standard treatment for metastatic colorectal cancer (MCRC). The aim of this study was to determine the efficacy and safety of capecitabine þ irinotecan (2-weekly schedule), as first-line therapy of MCRC. METHODS: Patients received irinotecan 175 mg m À2 on day 1 and oral capecitabine 1000 mg m À2 twice daily on days 2 -8 every 2 weeks. For patients aged X65 years, the starting doses of irinotecan and capecitabine were reduced to 140 and 750 mg m À2 , respectively. RESULTS: A total of 53 patients were enrolled: 29 (55%) were X65 years old. In an intention-to-treat analysis, complete response was achieved in three patients for an overall response rate (ORR) of 32%. The disease control rate (ORR þ stable disease) was 66% and the median duration of response was 7.3 months. Median time to progression and overall survival were 9.0 and 19.2 months, respectively. Grade 4 neutropenia was reported in one patient: no other grade 4 toxicities were recorded. Grade 3 diarrhoea occurred in 8 (15%) patients and grade 1 -2 hand -foot syndrome in 7 (13%) patients. CONCLUSION: Capecitabine and irinotecan, given every 2 weeks, as first-line treatment of MCRC is an active regimen with a manageable toxicity profile, even in older patients.

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Section: Discussionsupporting

confidence: 75%

Section: Discussioncontrasting

confidence: 48%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Capecitabine in combination with irinotecan (XELIRI), administered as a 2-weekly schedule, as first-line chemotherapy for patients with metastatic colorectal cancer: a phase II study of the Spanish GOTI group

et al. 2009

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“…Following these reports, this combination therapy was recognized as the standard chemotherapy for colorectal cancer. Nonetheless, several studies have attempted to use oral fluoropyrimidine derivatives such as capecitabine and S-1, instead of 5-FU plus leucovorin, in combination with CPT-11 (11)(12)(13)(14). These studies have also shown favorable results in terms of their efficacy and safety.…”

Section: Introductionmentioning

confidence: 99%

Phase I/II study of combination therapy with S-1 and CPT-11 for metastatic colorectal cancer

Nakafusa

Tanaka

Ohtsuka³

et al. 2008

Mol Med Rep

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Abstract. We conducted a Phase I/II study of combination therapy using CPT-11 and S-1 as a first-line treatment for metastatic colorectal cancer. The 28-day treatment cycle consisted of S-1 administered orally from day 1 to 21 and CPT-11 administered intravenously on days 1 and 15. In the Phase I portion, the dose of S-1 was fixed at 80 mg/m 2 /day, while CPT-11 was administered at a starting dose of 60 mg/m 2 then stepped up in 20 mg/m 2 increments. The maximumtolerated dose was achieved at 80 mg/m 2 of CPT-11, and the recommended dose was determined to be 60 mg/m 2 of CPT-11. In the Phase II portion, this therapy exhibited a response rate of 58%, a median progression-free survival of 8.4 months, and a median overall survival of 18.7 months. Toxicity was generally mild and manageable. No patient showed grade 4 toxicity, and grade 3 toxicity was observed in only 18% of patients. The most frequently observed grade 3 toxicity was diarrhea, at a rate of 6%. The mean relative dose intensity of CPT-11 and S-1 was as high as 98 and 97%, respectively. In conclusion, combination therapy with CPT-11 and S-1 according to our treatment schedule is effective, safe and highly feasible for metastatic colorectal cancer patients. These data suggest that assessing this combination therapy in a Phase III study would be worthwhile.

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Phase 1 Study of ABT‐751 in Combination With CAPIRI (Capecitabine and Irinotecan) and Bevacizumab in Patients With Advanced Colorectal Cancer

Rudek

Dasari

Laheru

et al. 2016

The Journal of Clinical Pharma

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ABT‐751 is an orally bioavailable sulfonamide with antimitotic properties. A nonrandomized phase 1 dose‐escalation study of ABT‐751 in combination with CAPIRI (capecitabine and irinotecan) and bevacizumab was conducted to define the maximum tolerated dose, dose‐limiting toxicity (DLT), and pharmacokinetics in patients with advanced colorectal cancer. Patients were treated with ABT‐751 daily for 7 days (alone) and then began 21‐day cycles of treatment with ABT‐751 daily and capecitabine twice daily for 14 days plus irinotecan on day 1 intravenously. Bevacizumab was added as standard of care at 7.5 mg/kg on day 1 after the first 2 dose levels. Because of intolerance to the regimen, a reduced dose of ABT‐751 was also explored with reduced‐dose and full‐dose CAPIRI with bevacizumab. ABT‐751 and irinotecan pharmacokinetics, ABT‐751 glucuronidation, and protein binding were explored. Twenty‐four patients were treated over 5 dose levels. The maximum tolerated dose was ABT‐751 125 mg combined with full‐dose CAPIRI and bevacizumab 7.5 mg/kg on day 1. DLTs were hypokalemia, elevated liver tests, and febrile neutropenia. ABT‐751 is metabolized by UGT1A8 and to a lesser extent UGT1A4 and UGT1A1. Irinotecan and APC exposure were increased, SN‐38 exposure was similar, and SN‐38 glucuronide exposure was decreased. Clinically relevant alterations in ABT‐751 and irinotecan pharmacokinetics were not observed. Despite modest efficacy, the combination of ABT‐751, CAPIRI, and bevacizumab will not be studied further in colorectal cancer.

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Capecitabine Plus 3-Weekly Irinotecan (XELIRI Regimen) as First-Line Chemotherapy for Metastatic Colorectal Cancer

Abstract: XELIRI is an active first-line treatment of MCRC. Implementation of upfront dose reductions for both agents in patients with risk factors for toxicity appears to have produced a safer regimen compared with previous studies of XELIRI without such dose reductions.

Cited by 50 publications

References 39 publications

Capecitabine in combination with irinotecan (XELIRI), administered as a 2-weekly schedule, as first-line chemotherapy for patients with metastatic colorectal cancer: a phase II study of the Spanish GOTI group

Capecitabine in combination with irinotecan (XELIRI), administered as a 2-weekly schedule, as first-line chemotherapy for patients with metastatic colorectal cancer: a phase II study of the Spanish GOTI group

Phase I/II study of combination therapy with S-1 and CPT-11 for metastatic colorectal cancer

Phase 1 Study of ABT‐751 in Combination With CAPIRI (Capecitabine and Irinotecan) and Bevacizumab in Patients With Advanced Colorectal Cancer

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