Abstract | PURPOSE: METHODS:
Bevacizumab was administered at escalating dosages of 2.5-11 mg/kg on days 1 and 15, and oral valproic acid at dosages of 5.3-10 mg/kg on days 1-28 every 28 days to determine the maximum tolerated dose. Pharmacodynamic parameters were assessed in peripheral blood mononuclear cells ( histone H3 acetylation) and serum ( valproic acid levels). RESULTS: Fifty-seven patients were enrolled. Dose-limiting toxicities were grade 3 altered mental status (n = 2), related to valproic acid. Bevacizumab 11 mg/kg given on days 1 and 15 and valproic acid 5.3 mg/kg daily were the recommended phase II dosages. Stable disease (SD) ≥6 months was reported in 4/57 (7 %) of patients, including two patients with colorectal cancer who had progressed previously on bevacizumab. Of the 39 patients evaluated for histone acetylation, 2 of 3 (67 %) patients with SD ≥6 months showed histone acetylation, while 8 of 36 (22 %) without SD ≥6 months demonstrated histone acetylation (p = 0.16). Patients with any grade of hypertension, compared to others, had a prolonged median survival (11.1 vs. 5.8 months; p = 0.012). CONCLUSIONS:
|
Authors | Jennifer J Wheler, Filip Janku, Gerald S Falchook, Tiffiny L Jackson, Siqing Fu, Aung Naing, Apostalia M Tsimberidou, Stacy L Moulder, David S Hong, Hui Yang, Sarina A Piha-Paul, Johnique T Atkins, Guillermo Garcia-Manero, Razelle Kurzrock |
Journal | Cancer chemotherapy and pharmacology
(Cancer Chemother Pharmacol)
Vol. 73
Issue 3
Pg. 495-501
(Mar 2014)
ISSN: 1432-0843 [Electronic] Germany |
PMID | 24435060
(Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, N.I.H., Extramural)
|
Chemical References |
- Angiogenesis Inhibitors
- Antibodies, Monoclonal, Humanized
- Histone Deacetylase Inhibitors
- Bevacizumab
- Valproic Acid
|
Topics |
- Adult
- Aged
- Aged, 80 and over
- Angiogenesis Inhibitors
(administration & dosage, adverse effects)
- Antibodies, Monoclonal, Humanized
(administration & dosage, adverse effects)
- Antineoplastic Combined Chemotherapy Protocols
(adverse effects, therapeutic use)
- Bevacizumab
- Dose-Response Relationship, Drug
- Female
- Histone Deacetylase Inhibitors
(administration & dosage, adverse effects)
- Humans
- Male
- Middle Aged
- Neoplasms
(blood supply, drug therapy)
- Valproic Acid
(administration & dosage, adverse effects)
|