5-Fluorouracil, Leucovorin and Oxaliplatin plus Bevacizumab in the First-Line Treatment of Metastatic Colorectal Cancer: A Single-Institute Study

Bir, Arvinder; Tan, Wei; Wilding, Gregory E.; Lombardo, Jeffrey; Fakih, Marwan

doi:10.1159/000110546

Cited by 15 publications

(22 citation statements)

References 28 publications

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confidence: 99%

“…The safety and efficacy of bevacizumab, the monoclonal antibody that targets vascular endothelial growth factor (VEGF; ref. 7), in combination with FOLFIRI or FOLFOX, was also evaluated recently (8,9). Although both studies were carried out with small patient numbers, Kang et al concluded that the combination treatment had modest activity and was relatively tolerable in metastatic colorectal cancer that had failed FOLFIRI or FOLFOX.…”

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confidence: 99%

“…Although both studies were carried out with small patient numbers, Kang et al concluded that the combination treatment had modest activity and was relatively tolerable in metastatic colorectal cancer that had failed FOLFIRI or FOLFOX. A retrospective study where bevacizumab and FOLFOX were used in first-line treatment of metastatic colorectal cancer (8) further indicated that the treatment improved time to disease progression and overall survival. The authors concluded that this combination should be explored further.…”

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confidence: 99%

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Irinophore C, a Novel Nanoformulation of Irinotecan, Alters Tumor Vascular Function and Enhances the Distribution of 5-Fluorouracil and Doxorubicin

Baker

Lam

Kyle

et al. 2008

Clinical Cancer Research

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Purpose: To examine the antitumor effects of Irinophore C, a nanopharmaceutical formulation of irinotecan, on the tissue morphology and function of tumor vasculature in HT-29 human colorectal tumors. Experimental Design: Fluorescence microscopy was used to map and quantify changes in tissue density, tumor vasculature, hypoxia, and the distribution of Hoechst 33342, a perfusion marker, and the anticancer drug, doxorubicin. Noninvasive magnetic resonance imaging was used to quantify K trans , the volume transfer constant of a solute between the blood vessels and extracellular tissue compartment of the tumor, as a measure of vascular function. Following treatment with Irinophore C, 19F magnetic resonance spectroscopy was used to monitor the delivery of 5-fluorouracil (5-FU) to the tumor tissue, whereas scintigraphy was used to quantify the presence of bound [ ), and 5-FU (P = 0.0002) in the tumor. Vascular endothelial growth factor and interleukin-8, two proangiogenic factors, were down-regulated, whereas the antiangiogenic factorTIMP-1was up-regulated in Irinophore C-treated tumors. Conclusions: Irinophore C treatment improves the vascular function of the tumor, thereby reducing tumor hypoxia and increasing the delivery and accumulation of a second drug. Reducing hypoxia would enhance radiotherapy, whereas improving delivery of a second drug to the tumor should result in higher cell kill.The clinical management of metastatic disease originating from colon/colorectal cancer remains challenging. The liver is the most common site of distant metastases for colorectal cancer, with 70% of patients presenting with liver metastases followed by the lungs, bone, and brain (1, 2). At present, the only cure is complete surgical removal of the primary tumor if diagnosed early; however, up to 45% of these patients still relapse with metastatic disease. Standard of care for first-line therapy in patients is a combination of 5-fluorouracil (5-FU; plus leucovorin) with either irinotecan (FOLFIRI) or oxaliplatin (FOLFOX; ref.3). The treatments are associated with prolonged median survivals of 18 to 21 months. Capecitabine, an oral fluoropyrimidine carbamate, has also been used in combination with 5-FU, and clinical data suggest that this combination is comparable with the FOLFIRI and FOLFOX regimens (4, 5). In practice, however, combination therapy with capecitabine is limited because of severe toxicities such as hand-foot syndrome, diarrhea, nausea, vomiting, and bone marrow suppression (4, 5). More recently, monoclonal antibodies targeting the epidermal growth factor receptor, such as cetuximab and panitumumab, have been used in combination with standard chemotherapy with promising results (6). The safety and efficacy of bevacizumab, the monoclonal antibody that targets vascular endothelial growth factor (VEGF; ref. 7), in combination with FOLFIRI or FOLFOX, was also evaluated recently (8,9). Although both studies were carried out with small Cancer Therapy: Preclinical

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Irinophore C, a Novel Nanoformulation of Irinotecan, Alters Tumor Vascular Function and Enhances the Distribution of 5-Fluorouracil and Doxorubicin

Baker

Lam

Kyle

et al. 2008

Clinical Cancer Research

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“…More recent studies combining FOLFOX or XELOX with bevacizumab report a grade 3 neuropathy rate of 7–10%, likely reflecting earlier discontinuation of oxaliplatin [13,14]. In this journal, we have also previously reported on our experience with first-line FOLFOX plus bevacizumab chemotherapy [16]. Sixteen percent of patients treated with this combination experienced grade 3 neuropathy and 49% discontinued oxaliplatin prior to progression due to neuropathy [16].…”

Section: Introductionmentioning

confidence: 94%

“…In this journal, we have also previously reported on our experience with first-line FOLFOX plus bevacizumab chemotherapy [16]. Sixteen percent of patients treated with this combination experienced grade 3 neuropathy and 49% discontinued oxaliplatin prior to progression due to neuropathy [16]. The high rate of limiting neuropathy associated with FOLFOX (or XELOX) chemotherapy has triggered the investigation of stop and go FOLFOX regimens where oxaliplatin is electively withdrawn after 3 months from initiation of treatment.…”

Section: Introductionmentioning

confidence: 99%

Stop and Go FOLFOX plus Bevacizumab Chemotherapy in the First-Line Treatment of Metastatic Colorectal Cancer

Vaidyanathan¹,

Groman²,

Wilding³

et al. 2010

Oncology

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Background: Infusional 5-fluorouracil, leucovorin and oxaliplatin (FOLFOX) plus bevacizumab chemotherapy is commonly implemented in the first-line treatment of metastatic colorectal cancer. A stop and go oxaliplatin strategy has been recommended to reduce oxaliplatin-associated neuropathy. Despite the acceptance of this strategy by community and academic practices, efficacy data with this approach are limited. Methods: We analyzed the efficacy of a stop and go FOLFOX regimen combined with bevacizumab in a single institute between January 2007 and December 2009. Oxaliplatin was withdrawn electively after 8 cycles of treatment and patients were maintained on 5-fluorouracil/leucovorin and bevacizumab until progression. When feasible, patients were rechallenged with oxaliplatin upon progression. Results: Sixty-seven patients were treated and analyzed for outcome. The response rate of this group was 58%. The median progression-free and overall survival was 10.6 and 26.7 months, respectively. The median duration of disease control in the 18-patient subgroup that was rechallenged with oxaliplatin was 21.2 months. Conclusions: Elective withdrawal of oxaliplatin after 8 cycles in the setting of FOLFOX and bevacizumab does not appear to compromise the activity of this regimen. A stop and go approach of FOLFOX plus bevacizumab is effective and may reduce treatment costs and toxicity in comparison with a continuous FOLFOX treatment strategy.

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Anti-proliferative activity of aguerin B and a new rare nor-guaianolide lactone isolated from the aerial parts of Centaurea deflexa

Chicca¹,

Tebano²,

Adinolfi³

et al. 2011

European Journal of Medicinal Chemistry

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5-Fluorouracil, Leucovorin and Oxaliplatin plus Bevacizumab in the First-Line Treatment of Metastatic Colorectal Cancer: A Single-Institute Study

Cited by 15 publications

References 28 publications

Irinophore C, a Novel Nanoformulation of Irinotecan, Alters Tumor Vascular Function and Enhances the Distribution of 5-Fluorouracil and Doxorubicin

Irinophore C, a Novel Nanoformulation of Irinotecan, Alters Tumor Vascular Function and Enhances the Distribution of 5-Fluorouracil and Doxorubicin

Stop and Go FOLFOX plus Bevacizumab Chemotherapy in the First-Line Treatment of Metastatic Colorectal Cancer

Anti-proliferative activity of aguerin B and a new rare nor-guaianolide lactone isolated from the aerial parts of Centaurea deflexa

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