Predictors of the efficacy of FOLFIRI plus bevacizumab as second-line treatment in metastatic colorectal cancer patients

Suenaga, Mitsukuni; Matsusaka, Satoshi; Ueno, Masashi; Yamamoto, Norio; Shinozaki, Eiji; Mizunuma, Nobuyuki; Yamaguchi, Toshiharu; Hatake, Kiyohiko

doi:10.1007/s00595-010-4432-8

Cited by 16 publications

(7 citation statements)

References 20 publications

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“…However, findings from the vatalanib study suggested that there was a trend towards better clinical outcomes in the subgroup of patients with high LDH (Van Cutsem et al , 2011b) and, together with our findings, indicate that high baseline LDH levels may be associated with improved patient outcomes. However, such findings have not been demonstrated in previous studies with bevacizumab (Suenaga et al , 2011; Scartozzi et al , 2012; Cetin et al , 2012). These inconsistencies may indicate that, rather than overall LDH expression, levels of specific isoforms of LDH may have a predictive influence on clinical outcomes.…”

Section: Discussioncontrasting

confidence: 69%

Cediranib with mFOLFOX6 vs bevacizumab with mFOLFOX6 in previously treated metastatic colorectal cancer

et al. 2013

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Background:Cediranib is a highly potent inhibitor of vascular endothelial growth factor (VEGF) signalling with activity against all three VEGF receptors. Bevacizumab is an anti-VEGF-A monoclonal antibody with clinical benefit in previously treated metastatic colorectal cancer (mCRC).Methods:Patients with mCRC who had progressed following first-line therapy were randomised 1 : 1 : 1 to modified (m)FOLFOX6 plus cediranib (20 or 30 mg day−1) or bevacizumab (10 mg kg−1 every 2 weeks). The primary objective was to compare progression-free survival (PFS) between treatment arms.Results:A total of 210 patients were included in the intent-to-treat (ITT) analysis (cediranib 20 mg, n=71; cediranib 30 mg, n=73; bevacizumab, n=66). Median PFS in the cediranib 20 mg, cediranib 30 mg and bevacizumab groups was 5.8, 7.2 and 7.8 months, respectively. There were no statistically significant differences between treatment arms for PFS (cediranib 20 mg vs bevacizumab: HR=1.28 (95% CI, 0.85–1.95; P=0.29); cediranib 30 mg vs bevacizumab: HR=1.17 (95% CI, 0.77–1.76; P=0.79)) or overall survival (OS). Grade ⩾3 adverse events were more common with cediranib 30 mg (91.8%) vs cediranib 20 mg (81.4%) or bevacizumab (84.8%).Conclusion:There were no statistically significant differences between treatment arms for PFS or OS. When combined with mFOLFOX6, the 20 mg day−1 dose of cediranib was better tolerated than the 30 mg day−1 dose.

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Section: Discussioncontrasting

confidence: 69%

Cediranib with mFOLFOX6 vs bevacizumab with mFOLFOX6 in previously treated metastatic colorectal cancer

et al. 2013

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“…Increased toxicity is not unexpected when biologics are added to combination therapy [4,10,13,18,[20][21][22][23]. Indeed, the addition of cetuximab to irinotecan in second line enhanced chemotherapy-related toxicities in terms of diarrhoea (28.4% versus 15.7%), fatigue (7.7% versus 3.3%) or neutropenia (31.8% versus 25.4%) [12].…”

Section: Discussionmentioning

confidence: 95%

Time course of safety and efficacy of aflibercept in combination with FOLFIRI in patients with metastatic colorectal cancer who progressed on previous oxaliplatin-based therapy

Ruff

Ferry

Lakomý

et al. 2015

European Journal of Cancer

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Background: Patients with metastatic colorectal cancer (mCRC) previously-treated with oxaliplatin benefit significantly from the addition of aflibercept to FOLFIRI in relation to overall survival, progression-free survival and response rate. Patients and methods: The results for efficacy and safety over the time course of the VEGF Trap (aflibercept) with irinotecan in colorectal cancer after failure of oxaliplatin regimen trial were analysed based on data from 1226 patients randomised to receive FOLFIRI plus either aflibercept (n = 612) or placebo (n = 614). Hazard ratios (HR) by 6-month time period were estimated using a piecewise Cox proportional hazard model. Severity of adverse events (AEs) was graded using National Cancer Institute Common Terminology Criteria, version 3.0. Results: The estimated probabilities of survival were 38.5% versus 30.9% at 18 months, 28.0% versus 18.7% at 24 months and 22.3% versus 12.0% at 30 months, for the afliberceptand placebo-treated arms, respectively. The proportional improvement in the HR over time was consistent with the survival probability results; survival at 24 months was improved by 50% and almost doubled at 30 months. The majority of worst-grade AEs occurred within the first four cycles of treatment and in a small percent of treatment cycles and were mostly reversible. Common chemotherapy-and anti-vascular epithelial growth factor (VEGF)-associated AEs occurred rarely and in a small proportion of cycles with the majority being of single occurrence.Conclusions: The addition of aflibercept to FOLFIRI showed a continued and persistent improvement in overall survival over time in patients with mCRC. Although grade 3-4 AEs were more frequent in the aflibercept arm, they occurred in early treatment cycles and decreased sharply following initial presentation.

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“…In many, if not all the clinical trials combining BV into 2nd-line chemotherapy for patients with mCRC, the standard dosage was either 5 mg/kg on day 1 per 2-week cycle or 7.5 mg/kg on day 1 per 3-week cycle. [ 5 , 6 , 8 , 9 ] In ECOG E3200 trial, the investigator used even higher dosage of BV, 10 mg/kg on day 1 every 2 weeks, to achieve improved OS of 12.9 months, and PFS of 7.3 months. [ 9 ] Unlike previous studies, in the current study, the dosage of BV used was 2.5 mg/kg on day 1 per 2-week cycle, only the half of regularly used dosage in other studies, or even the quarter of the dosage of BV in ECOG 3200 trial.…”

Section: Discussionmentioning

confidence: 99%

A phase II clinical study of combining FOLFIRI and bevacizumab plus erlotinib in 2nd-line chemotherapy for patients with metastatic colorectal cancer

Zhao

Rui

et al. 2017

Medicine

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We conducted an open-label single-arm phase II study by combining irinotecan (FOLFIRI) and bevacizumab (BV) plus erlotinib (ER) in 2nd-line chemotherapy for patients with metastatic colorectal cancer (mCRC).Eligible mCRC patients received 1st-line standard chemotherapy but still had progressive disease. They were given FOLFIRI plus BV at 2.5 mg/kg on day 1 per 2-week cycle, and daily 150 mg ER. The primary endpoint is progression-free survival (PFS).A total of 122 patients enrolled in the study. Among them, 55.7% were male patients and median age was 58.4 years (29–72 years). Median PFS was 7.1 months (95% CI 4.3–10.2). Median overall survival (OS) was 13.5 months (95% CI 9.7–16.4). No patients had complete responses, 24 patients had partial response (19.6%) and 59 had stable disease (48.4%). The most frequent adverse event (AE) was rash, with 66 patients (54.1%) had grade 3/4 rash. Other frequent grade 3/4 AEs were fatigue (n = 36, 29.5%), bleeding (n = 31, 25.4%), neutropenia (n = 23, 18.9%), and platelets (n = 14, 11.5%).Combining FOLFIRI and BV plus ER in 2nd-line chemotherapy is efficient to treat mCRC patients with acceptable safety.

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Predictors of the efficacy of FOLFIRI plus bevacizumab as second-line treatment in metastatic colorectal cancer patients

Abstract: The results of this study suggest that FOLFIRI plus BV is a viable option in second-line treatment for mCRC refractory to first-line FOLFOX (5-fluorouracil, leucovorin, oxaliplatin) alone, and indicate that CA125 might be a predictive biomarker for the outcome.

Cited by 16 publications

References 20 publications

Cediranib with mFOLFOX6 vs bevacizumab with mFOLFOX6 in previously treated metastatic colorectal cancer

Cediranib with mFOLFOX6 vs bevacizumab with mFOLFOX6 in previously treated metastatic colorectal cancer

Time course of safety and efficacy of aflibercept in combination with FOLFIRI in patients with metastatic colorectal cancer who progressed on previous oxaliplatin-based therapy

A phase II clinical study of combining FOLFIRI and bevacizumab plus erlotinib in 2nd-line chemotherapy for patients with metastatic colorectal cancer

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