Abstract | PURPOSE: PATIENTS AND METHODS: Twelve adult patients were enrolled four on each combination. rhuMAbVEGF, 3 mg/kg IV, was administered weekly for 8 weeks with (1) doxorubicin 50 mg/m(2) every 4 weeks; (2) carboplatin at area under the curve of 6 plus paclitaxel 175 mg/m(2) every 4 weeks; and (3) fluorouracil (5-FU) 500 mg/m(2) with leucovorin 20 mg/m(2) weekly, weeks 1 to 6 every 8 weeks. RESULTS: The median number of rhuMAbVEGF doses delivered was eight (range, four to eight doses). Grade 3 toxicities were diarrhea (one 5-FU patient), thrombocytopenia (two patients on carboplatin plus paclitaxel), and leukopenia (one patient on carboplatin plus paclitaxel). These toxicities were likely attributable to the chemotherapy component of the regimen. The mean (+/- SD) peak serum level of rhuMAbVEGF was 167 +/- 46 microg/mL, and the mean terminal half-life was 13 days. Total (free plus bound) serum VEGF levels increased from 51 +/- 39 pg/mL (day 0) to 211 +/- 112 (day 49) pg/mL. Three responding patients continued treatment with rhuMAbVEGF and chemotherapy, receiving the equivalent of 36, 20, and 40 total rhuMAbVEGF doses with no cumulative or late toxicities. CONCLUSION: rhuMAbVEGF can be safely combined with chemotherapy at doses associated with VEGF blockade and without apparent synergistic toxicity. Its contribution to the treatment of advanced solid tumors should be evaluated in randomized treatment trials.
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Authors | K Margolin, M S Gordon, E Holmgren, J Gaudreault, W Novotny, G Fyfe, D Adelman, S Stalter, J Breed |
Journal | Journal of clinical oncology : official journal of the American Society of Clinical Oncology
(J Clin Oncol)
Vol. 19
Issue 3
Pg. 851-6
(Feb 01 2001)
ISSN: 0732-183X [Print] United States |
PMID | 11157039
(Publication Type: Clinical Trial, Clinical Trial, Phase I, Journal Article)
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Chemical References |
- Antibodies, Monoclonal
- Endothelial Growth Factors
- Lymphokines
- Vascular Endothelial Growth Factor A
- Vascular Endothelial Growth Factors
- Doxorubicin
- Carboplatin
- Paclitaxel
- Leucovorin
- Fluorouracil
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Topics |
- Adult
- Aged
- Antibodies, Monoclonal
(adverse effects, pharmacology)
- Antineoplastic Combined Chemotherapy Protocols
(adverse effects, pharmacology)
- Carboplatin
(administration & dosage, adverse effects)
- Combined Modality Therapy
- Doxorubicin
(administration & dosage, adverse effects)
- Drug Administration Schedule
- Drug Interactions
- Endothelial Growth Factors
(antagonists & inhibitors, blood, immunology)
- Female
- Fluorouracil
(administration & dosage, adverse effects)
- Humans
- Infusions, Intravenous
- Leucovorin
(administration & dosage, adverse effects)
- Lymphokines
(antagonists & inhibitors, blood, immunology)
- Male
- Middle Aged
- Neoplasms
(blood supply, drug therapy, therapy)
- Paclitaxel
(administration & dosage, adverse effects)
- Vascular Endothelial Growth Factor A
- Vascular Endothelial Growth Factors
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