A phase I, pharmacokinetic and pharmacodynamic dose escalation trial of weekly paclitaxel with interferon-α2b in patients with solid tumors

被引:7
作者
Schneider, Bryan
Fukunaga, Anna
Murry, Daryl
Yoder, Christy
Fife, Karen
Foster, Anne
Rosenberg, Leslie
Kelich, Stephanie
Li, Lang
Sweeney, Christopher
机构
[1] Indiana Univ, Dept Med, Div Hematol Oncol, Indianapolis, IN 46202 USA
[2] Purdue Univ, Dept Pharm Practice, W Lafayette, IN 47907 USA
[3] Univ Iowa, Coll Pharm, Iowa City, IA 52242 USA
[4] Walther Canc Inst, Indianapolis, IN USA
[5] Indiana Univ, Dept Med, Div Biostat, Indianapolis, IN USA
关键词
D O I
10.1007/s00280-006-0264-z
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Purpose: Paclitaxel and interferon have demonstrated anti-angiogenic activity in vitro and in vivo. The toxicity, pharmacokinetics, and pharmacodynamics of paclitaxel with interferon-alpha 2b (IFN-alpha 2b) were assessed in patients with solid tumors to assess the feasibility of this novel anti-angiogenic regimen. Methods: IFN-alpha 2b (1 million units) was administered twice daily by subcutaneous injection. Paclitaxel was given weekly over 1h starting at 30 mg/m(2) and increased to 50 mg/m(2). Cycles were repeated every 4 weeks. Results: Nineteen patients with a variety of solid tumors were enrolled. Dose-limiting toxicity in cycle 1 was observed at 50 mg/m(2).Eleven patients were treated at 40 mg/m(2) with no undue toxicity. Pharmacokinetic parameter comparison studies were completed in 11 patients who received days 1 and 29 paclitaxel. Mean paclitaxel clearance and area under the curve (0-infinity) were not statistically different from days 1 to 29. There was a 50% increase in the average C-max from days 1 to 29. There was also a 73% decrease of matrix metalloproteinase-9 (MMP-9) levels in these 11 patients from days 1 to 29 (p < 0.0005). All three patients with cutaneous angiosarcomas experienced clinically meaningful remissions. In addition, minor responses were observed in one patient with heavily pretreated ovarian cancer and another with adrenocortical carcinoma. Conclusion: This trial details the inability to dose escalate to the maximum tolerated dose of weekly paclitaxel when combined with low-dose interferon. However, this low-dose regimen caused a significant decrease in MMP-9 and demonstrated anti-cancer activity in cutaneous angiosarcomas.
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页码:261 / 268
页数:8
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