Phase I/Pilot Study of SU5416 (Semaxinib) in Combination With Irinotecan/Bolus 5-FU/LV (IFL) in Patients With Metastatic Colorectal Cancer
@article{Lockhart2006PhaseIS, title={Phase I/Pilot Study of SU5416 (Semaxinib) in Combination With Irinotecan/Bolus 5-FU/LV (IFL) in Patients With Metastatic Colorectal Cancer}, author={A Craig Lockhart and Gillian F. Cropp and Jordan D. Berlin and Edwin F. Donnelly and Robert D Schumaker and Larry J. Schaaf and Kenneth R. Hande and Arthur C. Fleischer and Alison L. Hannah and Mace L. Rothenberg}, journal={American Journal of Clinical Oncology}, year={2006}, volume={29}, pages={109-115} }
Objectives:Determine the toxicity, tolerability, and pharmacokinetics of SU5416, a vascular endothelial growth factor receptor-2 (VEGFR-2) tyrosine kinase inhibitor, coadministered with bolus 5-fluorouracil (5-FU), leucovorin, and irinotecan (IFL) in untreated patients with metastatic colorectal cancer. Methods:SU5416 (85 or 145 mg/m2) was administered twice weekly throughout a 6-week period along with standard IFL (4 weeks on/2 weeks off). Plasma samples were assayed for SU5416, irinotecan…
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References
SHOWING 1-10 OF 41 REFERENCES
Irinotecan combined with bolus fluorouracil, continuous infusion fluorouracil, and high-dose leucovorin every two weeks (LV5FU2 regimen): a clinical dose-finding and pharmacokinetic study in patients with pretreated metastatic colorectal cancer.
- MedicineJournal of clinical oncology : official journal of the American Society of Clinical Oncology
- 1999
The biweekly CPT-11/LV5FU2 combination is feasible and safe, without overlapping toxicity.
Results of a Phase I dose-escalating study of the antiangiogenic agent, SU5416, in patients with advanced malignancies.
- Medicine, BiologyClinical cancer research : an official journal of the American Association for Cancer Research
- 2002
Higher baseline levels of urine VEGF were observed in the 4 patients who gained clinical benefit, suggesting this may be a useful marker for predicting response to anti-VEGF therapies, suggesting that a weekly schedule of SU5416 shows signs of biological activity and is well tolerated at doses up to 145 mg/m(2).
Phase I study of a weekly schedule of irinotecan, high-dose leucovorin, and infusional fluorouracil as first-line chemotherapy in patients with advanced colorectal cancer.
- MedicineJournal of clinical oncology : official journal of the American Society of Clinical Oncology
- 1999
The addition of CPT-11 to 5-FU24h/LV seems to improve the therapeutic efficacy in terms of tumor response with manageable toxicity, and the recommended doses for further studies are C PT-11 80 mg/m2, LV 500 mg/ m2, and 5-fu24h 2.6 g/m3 given on a weekly-times-six schedule followed by a 1-week rest period.
CPT-11 (irinotecan) addition to bimonthly, high-dose leucovorin and bolus and continuous-infusion 5-fluorouracil (FOLFIRI) for pretreated metastatic colorectal cancer. GERCOR.
- MedicineEuropean journal of cancer
- 1999
Dose-finding and pharmacokinetic study of cisplatin, gemcitabine, and SU5416 in patients with solid tumors.
- Medicine, BiologyJournal of clinical oncology : official journal of the American Society of Clinical Oncology
- 2002
Analysis of variables of the coagulation cascade and of vessel wall activation was performed in three patients and showed significant increases in thrombin generation and endothelial cell perturbation in a treatment cycle-dependent manner.
A randomized controlled trial of fluorouracil plus leucovorin, irinotecan, and oxaliplatin combinations in patients with previously untreated metastatic colorectal cancer.
- Medicine, BiologyJournal of clinical oncology : official journal of the American Society of Clinical Oncology
- 2004
The FOLFOX regimen of oxaliplatin and infused fluorouracil plus leucovorin was active and comparatively safe and should be considered as a standard therapy for patients with advanced colorectal cancer.
Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer.
- MedicineThe New England journal of medicine
- 2004
The addition of bevacizumab to fluorouracil-based combination chemotherapy results in statistically significant and clinically meaningful improvement in survival among patients with metastatic colorectal cancer.
Phase II Study of the Antiangiogenic Agent SU5416 in Patients with Advanced Soft Tissue Sarcomas
- Medicine, BiologyClinical Cancer Research
- 2004
Correlative studies suggest that VEGF receptor or KIT inhibition was incomplete in at least some cases, providing a possible explanation for the observed lack of activity against advanced soft tissue sarcoma.
Mortality associated with irinotecan plus bolus fluorouracil/leucovorin: summary findings of an independent panel.
- MedicineJournal of clinical oncology : official journal of the American Society of Clinical Oncology
- 2001
Close clinical monitoring, early recognition of toxicities and toxicity syndromes, aggressive therapeutic intervention, and withholding therapy in the presence of unresolved drug-related toxicities is recommended for patients receiving IFL or other intensive chemotherapy regimens.
Irinotecan (CPT-11) metabolism and disposition in cancer patients.
- Medicine, ChemistryClinical cancer research : an official journal of the American Association for Cancer Research
- 1998
Data indicate that half of the dose in urine and feces may constitute some further unknown nonextractable or nonfluorescent metabolites of the antitumor camptothecine derivative irinotecan, and should be of importance as a guide to further therapeutic evaluation of this drug.