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Phase I/II study of neoadjuvant bevacizumab with radiation therapy and 5-fluorouracil in patients with rectal cancer: initial results
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| Zeitschriftentitel: | Journal of Clinical Oncology |
|---|---|
| Personen und Körperschaften: | , , , , , , , , |
| In: | Journal of Clinical Oncology, 25, 2007, 18_suppl, S. 4041-4041 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
American Society of Clinical Oncology (ASCO)
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| Schlagwörter: |
| author_facet |
Willett, C. Duda, D. Boucher, Y. di Tomaso, E. Clark, J. Blaszkowsky, L. Czito, B. Bendell, J. Jain, R. Willett, C. Duda, D. Boucher, Y. di Tomaso, E. Clark, J. Blaszkowsky, L. Czito, B. Bendell, J. Jain, R. |
|---|---|
| author |
Willett, C. Duda, D. Boucher, Y. di Tomaso, E. Clark, J. Blaszkowsky, L. Czito, B. Bendell, J. Jain, R. |
| spellingShingle |
Willett, C. Duda, D. Boucher, Y. di Tomaso, E. Clark, J. Blaszkowsky, L. Czito, B. Bendell, J. Jain, R. Journal of Clinical Oncology Phase I/II study of neoadjuvant bevacizumab with radiation therapy and 5-fluorouracil in patients with rectal cancer: initial results Cancer Research Oncology |
| author_sort |
willett, c. |
| spelling |
Willett, C. Duda, D. Boucher, Y. di Tomaso, E. Clark, J. Blaszkowsky, L. Czito, B. Bendell, J. Jain, R. 0732-183X 1527-7755 American Society of Clinical Oncology (ASCO) Cancer Research Oncology http://dx.doi.org/10.1200/jco.2007.25.18_suppl.4041 <jats:p> 4041 </jats:p><jats:p> Background: A phase I/II study of neoadjuvant bevacizumab with 5-fluorouracil and radiation therapy in patients with locally advanced rectal cancer was undertaken to determine whether inhibition of VEGF is safe and has clinical benefits by enhancing chemo- radiation therapy. Methods: 22 patients with endoscopic ultrasound or surface coil MRI staged T3/T4 non-metastatic rectal cancer were enrolled from 2001–2006. All patients completed 4 cycles of neoadjuvant therapy including: 1) bevacizumab infusion (5 or 10 mg/kg) on day 1 of each cycle; 2) peripheral venous infusion 5-FU (225 mg/m<jats:sup>2</jats:sup>/24 hours) administration each treatment week of cycles 2 - 4; 3) external beam irradiation delivery (50.4 Gy in 28 fractions over 5.5 weeks); and 4) surgery 7 to 9 weeks after completion of all neoadjuvant therapy. Correlative studies were undertaken before and during the trial. We collected serial tumor biopsies, PET-FDG scans, and analyzed blood and urine for potential biomarkers. Results: Mean pre-therapy tumor size was 4.7 cm (2–9 cm). Post-treatment surgical specimens usually had well-demarcated shallow ulcerations with a mean diameter of 2.4 cm (0.7–6 cm). In response to the neoadjuvant regimen, all patients had significantly (p<0.01) decreased FDG-uptake by PET. Histologic examination showed no residual primary cancer in 5 patients (ypT0). Of 17 patients with residual disease, microscopic disease usually occurred as malignant glands embedded in fibrosis (ypT1 in 3 patients, ypT2 in 4 patients, ypT3 in 10 patients). Downstaging was seen in 12/22 tumors. 8 patients had microscopic nodal metastases. Bevacizumab alone and combined treatment were both associated with increased plasma VEGF and PlGF levels in 18/18 patients (P<0.01 at all 4 timepoints compared to baseline). Viable CECs were decreased by VEGF blockade at day 3 (P<0.01 compared to baseline), and peak CEC levels during treatment was correlated with histologic tumor response (2.77 [1.18–3.18] for T3 patients, n=9 versus 1.14 [0.82–1.53] for T0-T2 patients, n=12; p=0.05). Conclusions: Addition of bevacizumab at a dose of 5 mg/kg to standard chemo-radiation is safe in patients with locally advanced rectal cancer. Bevacizumab is active and the combined regimen yields promising results. </jats:p><jats:p> [Table: see text] </jats:p> Phase I/II study of neoadjuvant bevacizumab with radiation therapy and 5-fluorouracil in patients with rectal cancer: initial results Journal of Clinical Oncology |
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| title |
Phase I/II study of neoadjuvant bevacizumab with radiation therapy and 5-fluorouracil in patients with rectal cancer: initial results |
| title_unstemmed |
Phase I/II study of neoadjuvant bevacizumab with radiation therapy and 5-fluorouracil in patients with rectal cancer: initial results |
| title_full |
Phase I/II study of neoadjuvant bevacizumab with radiation therapy and 5-fluorouracil in patients with rectal cancer: initial results |
| title_fullStr |
Phase I/II study of neoadjuvant bevacizumab with radiation therapy and 5-fluorouracil in patients with rectal cancer: initial results |
| title_full_unstemmed |
Phase I/II study of neoadjuvant bevacizumab with radiation therapy and 5-fluorouracil in patients with rectal cancer: initial results |
| title_short |
Phase I/II study of neoadjuvant bevacizumab with radiation therapy and 5-fluorouracil in patients with rectal cancer: initial results |
| title_sort |
phase i/ii study of neoadjuvant bevacizumab with radiation therapy and 5-fluorouracil in patients with rectal cancer: initial results |
| topic |
Cancer Research Oncology |
| url |
http://dx.doi.org/10.1200/jco.2007.25.18_suppl.4041 |
| publishDate |
2007 |
| physical |
4041-4041 |
| description |
<jats:p> 4041 </jats:p><jats:p> Background: A phase I/II study of neoadjuvant bevacizumab with 5-fluorouracil and radiation therapy in patients with locally advanced rectal cancer was undertaken to determine whether inhibition of VEGF is safe and has clinical benefits by enhancing chemo- radiation therapy. Methods: 22 patients with endoscopic ultrasound or surface coil MRI staged T3/T4 non-metastatic rectal cancer were enrolled from 2001–2006. All patients completed 4 cycles of neoadjuvant therapy including: 1) bevacizumab infusion (5 or 10 mg/kg) on day 1 of each cycle; 2) peripheral venous infusion 5-FU (225 mg/m<jats:sup>2</jats:sup>/24 hours) administration each treatment week of cycles 2 - 4; 3) external beam irradiation delivery (50.4 Gy in 28 fractions over 5.5 weeks); and 4) surgery 7 to 9 weeks after completion of all neoadjuvant therapy. Correlative studies were undertaken before and during the trial. We collected serial tumor biopsies, PET-FDG scans, and analyzed blood and urine for potential biomarkers. Results: Mean pre-therapy tumor size was 4.7 cm (2–9 cm). Post-treatment surgical specimens usually had well-demarcated shallow ulcerations with a mean diameter of 2.4 cm (0.7–6 cm). In response to the neoadjuvant regimen, all patients had significantly (p<0.01) decreased FDG-uptake by PET. Histologic examination showed no residual primary cancer in 5 patients (ypT0). Of 17 patients with residual disease, microscopic disease usually occurred as malignant glands embedded in fibrosis (ypT1 in 3 patients, ypT2 in 4 patients, ypT3 in 10 patients). Downstaging was seen in 12/22 tumors. 8 patients had microscopic nodal metastases. Bevacizumab alone and combined treatment were both associated with increased plasma VEGF and PlGF levels in 18/18 patients (P<0.01 at all 4 timepoints compared to baseline). Viable CECs were decreased by VEGF blockade at day 3 (P<0.01 compared to baseline), and peak CEC levels during treatment was correlated with histologic tumor response (2.77 [1.18–3.18] for T3 patients, n=9 versus 1.14 [0.82–1.53] for T0-T2 patients, n=12; p=0.05). Conclusions: Addition of bevacizumab at a dose of 5 mg/kg to standard chemo-radiation is safe in patients with locally advanced rectal cancer. Bevacizumab is active and the combined regimen yields promising results. </jats:p><jats:p> [Table: see text] </jats:p> |
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| author | Willett, C., Duda, D., Boucher, Y., di Tomaso, E., Clark, J., Blaszkowsky, L., Czito, B., Bendell, J., Jain, R. |
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| description | <jats:p> 4041 </jats:p><jats:p> Background: A phase I/II study of neoadjuvant bevacizumab with 5-fluorouracil and radiation therapy in patients with locally advanced rectal cancer was undertaken to determine whether inhibition of VEGF is safe and has clinical benefits by enhancing chemo- radiation therapy. Methods: 22 patients with endoscopic ultrasound or surface coil MRI staged T3/T4 non-metastatic rectal cancer were enrolled from 2001–2006. All patients completed 4 cycles of neoadjuvant therapy including: 1) bevacizumab infusion (5 or 10 mg/kg) on day 1 of each cycle; 2) peripheral venous infusion 5-FU (225 mg/m<jats:sup>2</jats:sup>/24 hours) administration each treatment week of cycles 2 - 4; 3) external beam irradiation delivery (50.4 Gy in 28 fractions over 5.5 weeks); and 4) surgery 7 to 9 weeks after completion of all neoadjuvant therapy. Correlative studies were undertaken before and during the trial. We collected serial tumor biopsies, PET-FDG scans, and analyzed blood and urine for potential biomarkers. Results: Mean pre-therapy tumor size was 4.7 cm (2–9 cm). Post-treatment surgical specimens usually had well-demarcated shallow ulcerations with a mean diameter of 2.4 cm (0.7–6 cm). In response to the neoadjuvant regimen, all patients had significantly (p<0.01) decreased FDG-uptake by PET. Histologic examination showed no residual primary cancer in 5 patients (ypT0). Of 17 patients with residual disease, microscopic disease usually occurred as malignant glands embedded in fibrosis (ypT1 in 3 patients, ypT2 in 4 patients, ypT3 in 10 patients). Downstaging was seen in 12/22 tumors. 8 patients had microscopic nodal metastases. Bevacizumab alone and combined treatment were both associated with increased plasma VEGF and PlGF levels in 18/18 patients (P<0.01 at all 4 timepoints compared to baseline). Viable CECs were decreased by VEGF blockade at day 3 (P<0.01 compared to baseline), and peak CEC levels during treatment was correlated with histologic tumor response (2.77 [1.18–3.18] for T3 patients, n=9 versus 1.14 [0.82–1.53] for T0-T2 patients, n=12; p=0.05). Conclusions: Addition of bevacizumab at a dose of 5 mg/kg to standard chemo-radiation is safe in patients with locally advanced rectal cancer. Bevacizumab is active and the combined regimen yields promising results. </jats:p><jats:p> [Table: see text] </jats:p> |
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| spelling | Willett, C. Duda, D. Boucher, Y. di Tomaso, E. Clark, J. Blaszkowsky, L. Czito, B. Bendell, J. Jain, R. 0732-183X 1527-7755 American Society of Clinical Oncology (ASCO) Cancer Research Oncology http://dx.doi.org/10.1200/jco.2007.25.18_suppl.4041 <jats:p> 4041 </jats:p><jats:p> Background: A phase I/II study of neoadjuvant bevacizumab with 5-fluorouracil and radiation therapy in patients with locally advanced rectal cancer was undertaken to determine whether inhibition of VEGF is safe and has clinical benefits by enhancing chemo- radiation therapy. Methods: 22 patients with endoscopic ultrasound or surface coil MRI staged T3/T4 non-metastatic rectal cancer were enrolled from 2001–2006. All patients completed 4 cycles of neoadjuvant therapy including: 1) bevacizumab infusion (5 or 10 mg/kg) on day 1 of each cycle; 2) peripheral venous infusion 5-FU (225 mg/m<jats:sup>2</jats:sup>/24 hours) administration each treatment week of cycles 2 - 4; 3) external beam irradiation delivery (50.4 Gy in 28 fractions over 5.5 weeks); and 4) surgery 7 to 9 weeks after completion of all neoadjuvant therapy. Correlative studies were undertaken before and during the trial. We collected serial tumor biopsies, PET-FDG scans, and analyzed blood and urine for potential biomarkers. Results: Mean pre-therapy tumor size was 4.7 cm (2–9 cm). Post-treatment surgical specimens usually had well-demarcated shallow ulcerations with a mean diameter of 2.4 cm (0.7–6 cm). In response to the neoadjuvant regimen, all patients had significantly (p<0.01) decreased FDG-uptake by PET. Histologic examination showed no residual primary cancer in 5 patients (ypT0). Of 17 patients with residual disease, microscopic disease usually occurred as malignant glands embedded in fibrosis (ypT1 in 3 patients, ypT2 in 4 patients, ypT3 in 10 patients). Downstaging was seen in 12/22 tumors. 8 patients had microscopic nodal metastases. Bevacizumab alone and combined treatment were both associated with increased plasma VEGF and PlGF levels in 18/18 patients (P<0.01 at all 4 timepoints compared to baseline). Viable CECs were decreased by VEGF blockade at day 3 (P<0.01 compared to baseline), and peak CEC levels during treatment was correlated with histologic tumor response (2.77 [1.18–3.18] for T3 patients, n=9 versus 1.14 [0.82–1.53] for T0-T2 patients, n=12; p=0.05). Conclusions: Addition of bevacizumab at a dose of 5 mg/kg to standard chemo-radiation is safe in patients with locally advanced rectal cancer. Bevacizumab is active and the combined regimen yields promising results. </jats:p><jats:p> [Table: see text] </jats:p> Phase I/II study of neoadjuvant bevacizumab with radiation therapy and 5-fluorouracil in patients with rectal cancer: initial results Journal of Clinical Oncology |
| spellingShingle | Willett, C., Duda, D., Boucher, Y., di Tomaso, E., Clark, J., Blaszkowsky, L., Czito, B., Bendell, J., Jain, R., Journal of Clinical Oncology, Phase I/II study of neoadjuvant bevacizumab with radiation therapy and 5-fluorouracil in patients with rectal cancer: initial results, Cancer Research, Oncology |
| title | Phase I/II study of neoadjuvant bevacizumab with radiation therapy and 5-fluorouracil in patients with rectal cancer: initial results |
| title_full | Phase I/II study of neoadjuvant bevacizumab with radiation therapy and 5-fluorouracil in patients with rectal cancer: initial results |
| title_fullStr | Phase I/II study of neoadjuvant bevacizumab with radiation therapy and 5-fluorouracil in patients with rectal cancer: initial results |
| title_full_unstemmed | Phase I/II study of neoadjuvant bevacizumab with radiation therapy and 5-fluorouracil in patients with rectal cancer: initial results |
| title_short | Phase I/II study of neoadjuvant bevacizumab with radiation therapy and 5-fluorouracil in patients with rectal cancer: initial results |
| title_sort | phase i/ii study of neoadjuvant bevacizumab with radiation therapy and 5-fluorouracil in patients with rectal cancer: initial results |
| title_unstemmed | Phase I/II study of neoadjuvant bevacizumab with radiation therapy and 5-fluorouracil in patients with rectal cancer: initial results |
| topic | Cancer Research, Oncology |
| url | http://dx.doi.org/10.1200/jco.2007.25.18_suppl.4041 |