Abstract | PURPOSE: EXPERIMENTAL DESIGN:
Cediranib was administered daily orally at a starting dose of 30 mg and escalated to 45 mg daily, and mFOLFOX-6 was repeated every 14 days. Pharmacokinetic studies were done for oxaliplatin, 5-fluorouracil, and cediranib. Response was assessed by Response Evaluation Criteria in Solid Tumors every four cycles. RESULTS: Sixteen patients received 150 cycles of treatment (median, 6; range, 1-20 cycles). Of 9 patients enrolled at the 30-mg dose level, 1 patient experienced grade 3 diarrhea during cycle 1. No dose-limiting toxicity was observed in 7 patients at the 45-mg dose level. Common grade 3 toxicities related to cediranib included hypertension, diarrhea, fatigue, and anorexia. Of 14 patients evaluable for response, there were 6 partial responses (42.9%; 95% confidence interval, 17.7-71.1%) and 6 stable disease. The median progression-free survival was 9.3 months. There were no pharmacokinetic interactions between cediranib and 5-fluorouracil or free plasma intact oxaliplatin. CONCLUSIONS: Toxicities of this combination were manageable and consistent with previous studies. The recommended phase II dose is cediranib at 30 mg daily continuously in combination with standard doses of mFOLFOX-6. Cediranib and mFOLFOX-6 has promising antitumor activity and this combination warrants further investigation.
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Authors | Eric Chen, Derek Jonker, Isabelle Gauthier, Martha MacLean, Julie Wells, Jean Powers, Lesley Seymour |
Journal | Clinical cancer research : an official journal of the American Association for Cancer Research
(Clin Cancer Res)
Vol. 15
Issue 4
Pg. 1481-6
(Feb 15 2009)
ISSN: 1078-0432 [Print] United States |
PMID | 19228749
(Publication Type: Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Organoplatinum Compounds
- Quinazolines
- cediranib
- Leucovorin
- Fluorouracil
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Topics |
- Adult
- Aged
- Antineoplastic Combined Chemotherapy Protocols
(administration & dosage, adverse effects, pharmacokinetics)
- Colorectal Neoplasms
(drug therapy)
- Female
- Fluorouracil
(administration & dosage, adverse effects, pharmacokinetics)
- Humans
- Leucovorin
(administration & dosage, adverse effects, pharmacokinetics)
- Male
- Middle Aged
- Organoplatinum Compounds
(administration & dosage, adverse effects, pharmacokinetics)
- Quinazolines
(administration & dosage, adverse effects, pharmacokinetics)
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