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

Bryan Schneider, Anna Fukunaga, Daryl Murry, Christy Yoder, Karen Fife, Anne Foster, Leslie Rosenberg, Stephanie Kelich, Lang Li, Christopher Sweeney

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Purpose: Paclitaxel and interferon have demonstrated anti-angiogenic activity in vitro and in vivo. The toxicity, pharmacokinetics, and pharmacodynamics of paclitaxel with interferon-α2b (IFN-α2b) were assessed in patients with solid tumors to assess the feasibility of this novel anti-angiogenic regimen. Methods: IFN-α2b (1 million units) was administered twice daily by subcutaneous injection. Paclitaxel was given weekly over 1 h starting at 30 mg/m2 and increased to 50 mg/m2. 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/m2. Eleven patients were treated at 40 mg/m2 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-∞) were not statistically different from days 1 to 29. There was a 50% increase in the average Cmax 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.

Original languageEnglish
Pages (from-to)261-268
Number of pages8
JournalCancer Chemotherapy and Pharmacology
Volume59
Issue number2
DOIs
StatePublished - Feb 2007

Fingerprint

Pharmacodynamics
Pharmacokinetics
Paclitaxel
Interferons
Tumors
Toxicity
Neoplasms
Matrix Metalloproteinase 9
Hemangiosarcoma
Adrenocortical Carcinoma
Skin
Maximum Tolerated Dose
Subcutaneous Injections
Ovarian Neoplasms
Area Under Curve

ASJC Scopus subject areas

  • Cancer Research
  • Pharmacology
  • Oncology

Cite this

A phase I, pharmacokinetic and pharmacodynamic dose escalation trial of weekly paclitaxel with interferon-α2b in patients with solid tumors. / Schneider, Bryan; Fukunaga, Anna; Murry, Daryl; Yoder, Christy; Fife, Karen; Foster, Anne; Rosenberg, Leslie; Kelich, Stephanie; Li, Lang; Sweeney, Christopher.

In: Cancer Chemotherapy and Pharmacology, Vol. 59, No. 2, 02.2007, p. 261-268.

Research output: Contribution to journalArticle

Schneider, Bryan ; Fukunaga, Anna ; Murry, Daryl ; Yoder, Christy ; Fife, Karen ; Foster, Anne ; Rosenberg, Leslie ; Kelich, Stephanie ; Li, Lang ; Sweeney, Christopher. / A phase I, pharmacokinetic and pharmacodynamic dose escalation trial of weekly paclitaxel with interferon-α2b in patients with solid tumors. In: Cancer Chemotherapy and Pharmacology. 2007 ; Vol. 59, No. 2. pp. 261-268.
@article{883d217248d94501a424a8bd221f7e00,
title = "A phase I, pharmacokinetic and pharmacodynamic dose escalation trial of weekly paclitaxel with interferon-α2b in patients with solid tumors",
abstract = "Purpose: Paclitaxel and interferon have demonstrated anti-angiogenic activity in vitro and in vivo. The toxicity, pharmacokinetics, and pharmacodynamics of paclitaxel with interferon-α2b (IFN-α2b) were assessed in patients with solid tumors to assess the feasibility of this novel anti-angiogenic regimen. Methods: IFN-α2b (1 million units) was administered twice daily by subcutaneous injection. Paclitaxel was given weekly over 1 h starting at 30 mg/m2 and increased to 50 mg/m2. 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/m2. Eleven patients were treated at 40 mg/m2 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-∞) were not statistically different from days 1 to 29. There was a 50{\%} increase in the average Cmax 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.",
author = "Bryan Schneider and Anna Fukunaga and Daryl Murry and Christy Yoder and Karen Fife and Anne Foster and Leslie Rosenberg and Stephanie Kelich and Lang Li and Christopher Sweeney",
year = "2007",
month = "2",
doi = "10.1007/s00280-006-0264-z",
language = "English",
volume = "59",
pages = "261--268",
journal = "Cancer Chemotherapy and Pharmacology",
issn = "0344-5704",
publisher = "Springer Verlag",
number = "2",

}

TY - JOUR

T1 - A phase I, pharmacokinetic and pharmacodynamic dose escalation trial of weekly paclitaxel with interferon-α2b in patients with solid tumors

AU - Schneider, Bryan

AU - Fukunaga, Anna

AU - Murry, Daryl

AU - Yoder, Christy

AU - Fife, Karen

AU - Foster, Anne

AU - Rosenberg, Leslie

AU - Kelich, Stephanie

AU - Li, Lang

AU - Sweeney, Christopher

PY - 2007/2

Y1 - 2007/2

N2 - Purpose: Paclitaxel and interferon have demonstrated anti-angiogenic activity in vitro and in vivo. The toxicity, pharmacokinetics, and pharmacodynamics of paclitaxel with interferon-α2b (IFN-α2b) were assessed in patients with solid tumors to assess the feasibility of this novel anti-angiogenic regimen. Methods: IFN-α2b (1 million units) was administered twice daily by subcutaneous injection. Paclitaxel was given weekly over 1 h starting at 30 mg/m2 and increased to 50 mg/m2. 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/m2. Eleven patients were treated at 40 mg/m2 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-∞) were not statistically different from days 1 to 29. There was a 50% increase in the average Cmax 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.

AB - Purpose: Paclitaxel and interferon have demonstrated anti-angiogenic activity in vitro and in vivo. The toxicity, pharmacokinetics, and pharmacodynamics of paclitaxel with interferon-α2b (IFN-α2b) were assessed in patients with solid tumors to assess the feasibility of this novel anti-angiogenic regimen. Methods: IFN-α2b (1 million units) was administered twice daily by subcutaneous injection. Paclitaxel was given weekly over 1 h starting at 30 mg/m2 and increased to 50 mg/m2. 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/m2. Eleven patients were treated at 40 mg/m2 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-∞) were not statistically different from days 1 to 29. There was a 50% increase in the average Cmax 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.

UR - http://www.scopus.com/inward/record.url?scp=33845359789&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33845359789&partnerID=8YFLogxK

U2 - 10.1007/s00280-006-0264-z

DO - 10.1007/s00280-006-0264-z

M3 - Article

C2 - 16733646

AN - SCOPUS:33845359789

VL - 59

SP - 261

EP - 268

JO - Cancer Chemotherapy and Pharmacology

JF - Cancer Chemotherapy and Pharmacology

SN - 0344-5704

IS - 2

ER -