Characterization of the long-term pharmacokinetics of bevacizumab following last dose in patients with resected stage II and III carcinoma of the colon

Li, Jing; Gupta, Manish; Jin, Denise; Yan, Xin; Visich, Jennifer; Allison, David E.

doi:10.1007/s00280-012-2031-7

Cited by 24 publications

(23 citation statements)

References 18 publications

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“…Bevacizumab pharmacokinetics is well established in phase-I, -II, and -III studies as a single agent or in combination with chemotherapy for both single- and multiple-dose administration with both rich and sparse bevacizumab serum concentration data (14–17). Bevacizumab pharmacokinetics showed dose linearity within the dose range of 1–20 mg/kg, a slow clearance, a volume of distribution consistent with limited extravascular distribution, and a terminal half life of approximately 20 days.…”

Section: Introductionmentioning

confidence: 99%

“…Bevacizumab pharmacokinetics showed dose linearity within the dose range of 1–20 mg/kg, a slow clearance, a volume of distribution consistent with limited extravascular distribution, and a terminal half life of approximately 20 days. Short-term ( e.g ., up to 30 days after dose) and long-term (up to 6 months after dose) pharmacokinetics of bevacizumab is comparable (17). A population pharmacokinetic model has been previously established in metastatic colorectal, breast, non-small cell lung, and prostate cancer, and showed that bevacizumab pharmacokinetics is consistent across these cancers (15).…”

Section: Introductionmentioning

confidence: 99%

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Lower Exposure and Faster Clearance of Bevacizumab in Gastric Cancer and the Impact of Patient Variables: Analysis of Individual Data from AVAGAST Phase III Trial

Han¹,

Jin²,

Maia³

et al. 2014

AAPS J

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Altered pharmacokinetics of antibody drugs has been reported in advanced gastric cancer (AGC). We aim to evaluate bevacizumab pharmacokinetics in AGC from the Phase III trial (AVAGAST), and explore the influence of patient variables. Bevacizumab concentrations (Cp) were measured in plasma samples taken following disease progression from 162 patients (7.5 mg/kg every 3 weeks). Predicted Cp [median and 90% prediction interval] was simulated using the population pharmacokinetic model established for other cancers (PPK model) and compared to observed Cp. Bevacizumab clearance was estimated using NONMEM and compared between subgroups. Patient characteristics of AGC are similar to other cancers except for lower body weight despite higher percentage of males. Eighty-five percent of observed Cp was below the median predicted Cp and 38% below the lower boundary of the 90% prediction interval. Median bevacizumab clearance in AGC was 4.5 versus 3 mL/day/kg in other cancers. Bevacizumab clearance was significantly faster (p < 0.05) in patients without gastrectomy (n = 42) or lower albumin. Clearance appeared to be faster in patients with lower total protein, higher ECOG scores, more metastatic sites, and poorer response. No significant difference in bevacizumab concentrations and clearance was observed between Asian and Non-Asian patients. AGC patients exhibited significantly lower bevacizumab exposure due to an approximate 50% increase in clearance versus other cancers. Bevacizumab is cleared faster in patients without prior gastrectomy. No significant difference in bevacizumab pharmacokinetics was observed between Asian and Non-Asian patients. The underlying mechanism for faster bevacizumab clearance in AGC is unknown and warrants further research.Electronic supplementary materialThe online version of this article (doi:10.1208/s12248-014-9631-6) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Lower Exposure and Faster Clearance of Bevacizumab in Gastric Cancer and the Impact of Patient Variables: Analysis of Individual Data from AVAGAST Phase III Trial

Han¹,

Jin²,

Maia³

et al. 2014

AAPS J

Self Cite

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“…A long-term pharmacokinetics study demonstrated extended serum persistence of bevacizumab following termination of bevacizumab 3 and 6 months after the last administration, which may affect clinical outcomes of post-bevacizumab treatment (12). This prompted us to investigate the impact of shorter intervals between bevacizumab and anti-EGFR therapy on the efficacy of subsequent anti-EGFR therapy.…”

Section: Introductionmentioning

confidence: 99%

A short interval between bevacizumab and anti-epithelial growth factor receptor therapy interferes with efficacy of subsequent anti-EGFR therapy for refractory colorectal cancer

Taniguchi

Komori

Kadowaki

et al. 2016

Jpn. J. Clin. Oncol.

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Background: Both bevacizumab and anti-epithelial growth factor receptor (EGFR) agents (e.g. cetuximab and panitumumab) are sequentially used for metastatic colorectal cancer (mCRC). Their coadministration as a first-line treatment does not improve outcome, indicating that there are negative interactions between these agents. A long-term pharmacokinetics study demonstrated serum persistence of bevacizumab following termination of bevacizumab 6 months after the last administration. This prompted us to investigate the impact of short intervals between bevacizumab and anti-EGFR antibody on the efficacy of subsequent anti-EGFR therapy. Methods: We retrospectively reviewed consecutive patients with KRAS exon 2 wild-type mCRC who underwent anti-EGFR therapy after the failure of fluoropyrimidines, oxaliplatin and irinotecan. We divided patients into two groups (Group A: the interval between bevacizumab and anti-EGFR agent< 6 months; Group B: the interval >6 months). Results: Of the 114 included patients (median age, 63 years), 78 (68%) were male. Most patients (88%) were treated with cetuximab plus irinotecan. Groups A and B consisted of 74 and 40 patients, respectively. There were no significant differences in patient characteristics. Group B patients had significantly longer progression-free survival (4.2 vs. 6.6 months; HR, 0.65; 95% CI, 0.43-0.98; P = 0.038) and longer overall survival (11.6 vs. 14.3 months; HR, 0.63; 95% CI, 0.41-0.98, P = 0.039). The response rate was 24.3% in Group A and 47.5% in Group B (P = 0.012). Conclusion: A short interval between bevacizumab and anti-EGFR antibody treatment may interfere with the efficacy of subsequent anti-EGFR therapy.

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“…The results of previous reports also support our findings. We speculated that a BFI cutoff of 6 months is an efficient scale for evaluating the interaction between bevacizumab and anti-EGFR antibodies, because previous reports demonstrated that bevacizumab was detected in plasma at 6 months after the last administration [27]. CAIRO2 and PACCE, two previous prospective studies that evaluated the efficacy of bevacizumab and anti-EGFR antibodies combination therapy, failed to show a survival benefit [28,29].…”

Section: Discussionmentioning

confidence: 99%

Panitumumab Provides Better Survival Outcomes Compared to Cetuximab for Metastatic Colorectal Cancer Patients Treated with Prior Bevacizumab within 6 Months

Hayashi¹,

Mitani

Taniguchi

et al. 2018

Oncology

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Objective: Anti-epithelial growth factor receptor (EGFR) antibodies cetuximab (Cmab) and panitumumab (Pmab) have shown survival benefit for metastatic colorectal cancer (mCRC) patients. This study aimed to compare Pmab and Cmab according to the interval between bevacizumab discontinuation and anti-EGFR antibody initiation (bevacizumab-free interval; BFI). Methods: We retrospectively evaluated mCRC patients who received Cmab or Pmab in combination with irinotecan at two institutions. Inclusion criteria were histologically confirmed mCRC, with KRAS exon 2 wild-type tumor, refractory or intolerant to fluoropyrimidines, oxali platin, and irinotecan. Results: One-hundred-seventy-eight patients fulfilled the eligibility criteria. Among them, there was no significant difference in overall survival (OS) and progression-free survival (PFS) between the Pmab (n = 44) and Cmab groups (n = 134). Of 132 patients with BFI < 6 months, the median OS was 13.3 and 11.5 months in the Pmab (n = 39) and Cmab (n = 93) groups, respectively (p = 0.043). The median PFS was 5.8 and 4.9 months in the Pmab and Cmab groups, respectively (p = 0.055). Multivariate analysis for OS confirmed the superiority of Pmab. Conclusion: Pmab showed more favorable outcomes in patients treated with bevacizumab within the last 6 months. The interval between prior bevacizumab and subsequent anti-EGFR therapy may be useful for determining the optimal anti-EGFR therapy.

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Characterization of the long-term pharmacokinetics of bevacizumab following last dose in patients with resected stage II and III carcinoma of the colon

Cited by 24 publications

References 18 publications

Lower Exposure and Faster Clearance of Bevacizumab in Gastric Cancer and the Impact of Patient Variables: Analysis of Individual Data from AVAGAST Phase III Trial

Lower Exposure and Faster Clearance of Bevacizumab in Gastric Cancer and the Impact of Patient Variables: Analysis of Individual Data from AVAGAST Phase III Trial

A short interval between bevacizumab and anti-epithelial growth factor receptor therapy interferes with efficacy of subsequent anti-EGFR therapy for refractory colorectal cancer

Panitumumab Provides Better Survival Outcomes Compared to Cetuximab for Metastatic Colorectal Cancer Patients Treated with Prior Bevacizumab within 6 Months

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