Phase I Study and Pharmacokinetics of Weekly High-Dose 13-c/s-Retinoic Acid

Gerald Clamon, Guy G. Chabot, Frederick Valeriote, Enrique Davilla, Charles Vogel, Elizabeth Gorowski, Robert Birch

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

In an attempt to increase the peak plasma levels of 13-c/s-retinoic acid (13-c/s-RA) and its efficacy in vivo, a Phase I study and pharmacokinetics of weekly high-dose, oral 13-c/s-RA was conducted in 23 cancer patients who were refractory to conventional treatments. At 200 mg/sq m, the mean peak plasma level of 13-c/s-RA was 1.5 ± 0.1 (SE) u.g/m\\ at 400 mg/sq m, the mean peak plasma level increased to 3.8 ± 0.7 ng/m\. Further increases of the 13-c/s-RA dose up to 1800 mg/sq m did not lead to proportional increases in either the mean peak plasma levels or area under the curve, indicating a saturable absorption phenomenon. The terminal half-life was highly variable (range, 2.8 to 101.3 h) and was not related to the dose given. A secondary peak plasma concentration was seen in five patients, suggesting enterohepatic circulation. The toxicities such as headache, cheilitis, dry skin, and dry eyes were frequent on the weekly schedule but were not dose-limiting. One patient had an elevation of the triglycerides of 2 to 5 times the upper limit of normal; five patients had an elevation of 1.1 to 2 times normal. No objective responses were observed to treatment with 13-c/s-RA. Of 20 patients receiving an adequate trial of the drug, 18 showed progression of their cancer, and two had stable disease.

Original languageEnglish (US)
Pages (from-to)1874-1878
Number of pages5
JournalCancer Research
Volume45
Issue number4
StatePublished - Apr 1 1985
Externally publishedYes

Fingerprint

Tretinoin
Pharmacokinetics
Cheilitis
Enterohepatic Circulation
Area Under Curve
Headache
Half-Life
Neoplasms
Appointments and Schedules
Triglycerides
Skin
Therapeutics
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Clamon, G., Chabot, G. G., Valeriote, F., Davilla, E., Vogel, C., Gorowski, E., & Birch, R. (1985). Phase I Study and Pharmacokinetics of Weekly High-Dose 13-c/s-Retinoic Acid. Cancer Research, 45(4), 1874-1878.

Phase I Study and Pharmacokinetics of Weekly High-Dose 13-c/s-Retinoic Acid. / Clamon, Gerald; Chabot, Guy G.; Valeriote, Frederick; Davilla, Enrique; Vogel, Charles; Gorowski, Elizabeth; Birch, Robert.

In: Cancer Research, Vol. 45, No. 4, 01.04.1985, p. 1874-1878.

Research output: Contribution to journalArticle

Clamon, G, Chabot, GG, Valeriote, F, Davilla, E, Vogel, C, Gorowski, E & Birch, R 1985, 'Phase I Study and Pharmacokinetics of Weekly High-Dose 13-c/s-Retinoic Acid', Cancer Research, vol. 45, no. 4, pp. 1874-1878.
Clamon G, Chabot GG, Valeriote F, Davilla E, Vogel C, Gorowski E et al. Phase I Study and Pharmacokinetics of Weekly High-Dose 13-c/s-Retinoic Acid. Cancer Research. 1985 Apr 1;45(4):1874-1878.
Clamon, Gerald ; Chabot, Guy G. ; Valeriote, Frederick ; Davilla, Enrique ; Vogel, Charles ; Gorowski, Elizabeth ; Birch, Robert. / Phase I Study and Pharmacokinetics of Weekly High-Dose 13-c/s-Retinoic Acid. In: Cancer Research. 1985 ; Vol. 45, No. 4. pp. 1874-1878.
@article{4d74c742be15482b831e098c8e0923d6,
title = "Phase I Study and Pharmacokinetics of Weekly High-Dose 13-c/s-Retinoic Acid",
abstract = "In an attempt to increase the peak plasma levels of 13-c/s-retinoic acid (13-c/s-RA) and its efficacy in vivo, a Phase I study and pharmacokinetics of weekly high-dose, oral 13-c/s-RA was conducted in 23 cancer patients who were refractory to conventional treatments. At 200 mg/sq m, the mean peak plasma level of 13-c/s-RA was 1.5 ± 0.1 (SE) u.g/m\\ at 400 mg/sq m, the mean peak plasma level increased to 3.8 ± 0.7 ng/m\. Further increases of the 13-c/s-RA dose up to 1800 mg/sq m did not lead to proportional increases in either the mean peak plasma levels or area under the curve, indicating a saturable absorption phenomenon. The terminal half-life was highly variable (range, 2.8 to 101.3 h) and was not related to the dose given. A secondary peak plasma concentration was seen in five patients, suggesting enterohepatic circulation. The toxicities such as headache, cheilitis, dry skin, and dry eyes were frequent on the weekly schedule but were not dose-limiting. One patient had an elevation of the triglycerides of 2 to 5 times the upper limit of normal; five patients had an elevation of 1.1 to 2 times normal. No objective responses were observed to treatment with 13-c/s-RA. Of 20 patients receiving an adequate trial of the drug, 18 showed progression of their cancer, and two had stable disease.",
author = "Gerald Clamon and Chabot, {Guy G.} and Frederick Valeriote and Enrique Davilla and Charles Vogel and Elizabeth Gorowski and Robert Birch",
year = "1985",
month = "4",
day = "1",
language = "English (US)",
volume = "45",
pages = "1874--1878",
journal = "Journal of Cancer Research",
issn = "0099-7013",
publisher = "American Association for Cancer Research Inc.",
number = "4",

}

TY - JOUR

T1 - Phase I Study and Pharmacokinetics of Weekly High-Dose 13-c/s-Retinoic Acid

AU - Clamon, Gerald

AU - Chabot, Guy G.

AU - Valeriote, Frederick

AU - Davilla, Enrique

AU - Vogel, Charles

AU - Gorowski, Elizabeth

AU - Birch, Robert

PY - 1985/4/1

Y1 - 1985/4/1

N2 - In an attempt to increase the peak plasma levels of 13-c/s-retinoic acid (13-c/s-RA) and its efficacy in vivo, a Phase I study and pharmacokinetics of weekly high-dose, oral 13-c/s-RA was conducted in 23 cancer patients who were refractory to conventional treatments. At 200 mg/sq m, the mean peak plasma level of 13-c/s-RA was 1.5 ± 0.1 (SE) u.g/m\\ at 400 mg/sq m, the mean peak plasma level increased to 3.8 ± 0.7 ng/m\. Further increases of the 13-c/s-RA dose up to 1800 mg/sq m did not lead to proportional increases in either the mean peak plasma levels or area under the curve, indicating a saturable absorption phenomenon. The terminal half-life was highly variable (range, 2.8 to 101.3 h) and was not related to the dose given. A secondary peak plasma concentration was seen in five patients, suggesting enterohepatic circulation. The toxicities such as headache, cheilitis, dry skin, and dry eyes were frequent on the weekly schedule but were not dose-limiting. One patient had an elevation of the triglycerides of 2 to 5 times the upper limit of normal; five patients had an elevation of 1.1 to 2 times normal. No objective responses were observed to treatment with 13-c/s-RA. Of 20 patients receiving an adequate trial of the drug, 18 showed progression of their cancer, and two had stable disease.

AB - In an attempt to increase the peak plasma levels of 13-c/s-retinoic acid (13-c/s-RA) and its efficacy in vivo, a Phase I study and pharmacokinetics of weekly high-dose, oral 13-c/s-RA was conducted in 23 cancer patients who were refractory to conventional treatments. At 200 mg/sq m, the mean peak plasma level of 13-c/s-RA was 1.5 ± 0.1 (SE) u.g/m\\ at 400 mg/sq m, the mean peak plasma level increased to 3.8 ± 0.7 ng/m\. Further increases of the 13-c/s-RA dose up to 1800 mg/sq m did not lead to proportional increases in either the mean peak plasma levels or area under the curve, indicating a saturable absorption phenomenon. The terminal half-life was highly variable (range, 2.8 to 101.3 h) and was not related to the dose given. A secondary peak plasma concentration was seen in five patients, suggesting enterohepatic circulation. The toxicities such as headache, cheilitis, dry skin, and dry eyes were frequent on the weekly schedule but were not dose-limiting. One patient had an elevation of the triglycerides of 2 to 5 times the upper limit of normal; five patients had an elevation of 1.1 to 2 times normal. No objective responses were observed to treatment with 13-c/s-RA. Of 20 patients receiving an adequate trial of the drug, 18 showed progression of their cancer, and two had stable disease.

UR - http://www.scopus.com/inward/record.url?scp=0021794412&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0021794412&partnerID=8YFLogxK

M3 - Article

C2 - 3978647

AN - SCOPUS:0021794412

VL - 45

SP - 1874

EP - 1878

JO - Journal of Cancer Research

JF - Journal of Cancer Research

SN - 0099-7013

IS - 4

ER -