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Ref Type Journal Article
PMID (9815717)
Authors Schwartz GK, Ward D, Saltz L, Casper ES, Spiess T, Mullen E, Woodworth J, Venuti R, Zervos P, Storniolo AM, Kelsen DP
Title A pilot clinical/pharmacological study of the protein kinase C-specific inhibitor safingol alone and in combination with doxorubicin.
Journal Vol Issue Date Pages Journal Short Title
Clinical cancer research : an official journal of the American Association for Cancer Research 3 4 1997 Apr 537-43 Clin Cancer Res
URL
Abstract Text We performed a pilot clinical trial with safingol (L-threo-dihydrosphingosine), a protein kinase C-specific inhibitor that potentiates the effect of doxorubicin (DOX) in tumor-bearing animals. Safingol was initially administered as a 1-h infusion at escalating doses. Fourteen days later, patients received the same dose of safingol in combination with a fixed dose of DOX. The combination was repeated at 3-week intervals. Safingol dose levels ranged from 15 to 120 mg/m2. The plasma levels achieved at the final dose level were comparable to those associated with potentiation of DOX in animals. The mean Cmax and area under the curve for safingol at the 120 mg/m2 dose level were 1040 +/- 196 ng/ml and 1251 +/- 317 mg x h/ml, respectively. The mean plasma half-life for safingol was 3.97 +/- 2.51 h, the mean estimated clearance was 3140 +/- 765 ml/min, and the mean volume of distribution was of 995 +/- 421 liters. Coadministration of a fixed dose of DOX did not significantly change the pharmacokinetics of safingol, nor did increasing doses of safingol significantly affect the pharmacokinetics of DOX. Minor responses were observed in three patients with pancreatic cancer and one patient with angiosarcoma of the scalp. This pilot Phase I study indicates that the protein kinase C inhibitor safingol can be given safely with 45 mg/m2 of DOX at a dose that is potentially pharmacologically active without dose-limiting toxicity.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Safingol Safingol 0 1
Drug Name Trade Name Synonyms Drug Classes Drug Description
Safingol Kynacyte|Sphinganine PKC Inhibitor (Pan) 11 Kynacyte (safingol) inhibits protein kinase C (PKC), potentially resulting in increased tumor cell death and increased sensitivity to other anti-cancer agents (PMID: 15929099, PMID: 9815717).
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References