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Phase I trial of 9-cis retinoic acid in adults with solid tumors.
Kurie, J M; Lee, J S; Griffin, T; Lippman, S M; Drum, P; Thomas, M P; Weber, C; Bader, M; Massimini, G; Hong, W K.
Affiliation
  • Kurie JM; Department of Thoracic/Head and Neck Medical Oncology, Division of Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA.
Clin Cancer Res ; 2(2): 287-93, 1996 Feb.
Article in En | MEDLINE | ID: mdl-9816171
ABSTRACT
Retinoids have been shown to be potent inhibitors of epithelial carcinogenesis. Recent evidence has demonstrated that retinoid actions are mediated through nuclear receptors, which are proteins encoded by the retinoic acid receptor and retinoid X receptor gene families. These receptors are activated by binding to specific retinoids; of the known naturally occurring retinoids, 9-cis retinoic acid is unique in its ability to bind to both receptor families. Because of its unique receptor-binding characteristics, 9-cis retinoic acid may have biological activity not possible with other retinoids. For this reason, we conducted a Phase I trial of 9-cis retinoic acid in adult patients with solid tumors. Twenty-two patients were treated twice daily with p.o. 9-cis retinoic acid at doses ranging from 20 mg/m2/day to 150 mg/m2/day. The patients had non-small cell lung cancer (n = 8), breast cancer (n = 5), colorectal cancer (n = 3), head and neck cancer (n = 2), nonmelanoma skin cancer (n = 2), or ovarian cancer (n = 2). The dose-limiting (WHO grade III) toxic effects, which occurred at the 150-mg/m2/day dose level, were headaches and diarrhea. Less severe (grades I and II) toxic effects included cheilitis, dry skin, conjunctivitis, fatigue, hypertriglyceridemia, alkaline phosphatase elevation, myalgia/arthralgia, and hypercalcemia. Of the 15 patients evaluable for tumor response, no objective responses were observed. Pharmacokinetic analysis revealed a reduction in peak 9-cis retinoic acid plasma levels with chronic administration. Based on this study, the recommended Phase II dose of 9-cis retinoic acid in adult patients with solid tumors is 100 mg/m2/day administered in a divided dose twice daily.
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Collection: 01-internacional Database: MEDLINE Main subject: Tretinoin / Neoplasms / Antineoplastic Agents Limits: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Language: En Journal: Clin Cancer Res Journal subject: NEOPLASIAS Year: 1996 Document type: Article Affiliation country:
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Collection: 01-internacional Database: MEDLINE Main subject: Tretinoin / Neoplasms / Antineoplastic Agents Limits: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Language: En Journal: Clin Cancer Res Journal subject: NEOPLASIAS Year: 1996 Document type: Article Affiliation country: