ArticleInvestigational new drugs2007
A phase I study of oral LY293111 given daily in combination with irinotecan in patients with solid tumours.
Article in Investigational new drugs, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 30 citations in OpenAlex.
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- Involvement of eicosanoids in the pathogenesis of pancreatic cancer: the roles of cyclooxygenase-2 and 5-lipoxygenase.World journal of gastroenterology · 2014Review
- The role of peroxisome proliferator-activated receptors in carcinogenesis and chemoprevention.Nature reviews. Cancer · 2012Review
- The Key to Unlocking the Chemotherapeutic Potential of PPARγ Ligands: Having the Right Combination.PPAR research · 2012Article
- Peroxisome Proliferator-Activated Receptor-γ Ligands Alter Breast Cancer Cell Motility through Modulation of the Plasminogen Activator System.Journal of oncology · 2011Article
- Development and validation of a model that predicts early death among cancer patients participating in phase I clinical trials investigating cytotoxics.Investigational new drugs · 2010Article
- Current understanding of the role of PPARγ in gastrointestinal cancers.PPAR research · 2009Article
- Prognostic and therapeutic potential of nuclear receptors in head and neck squamous cell carcinomas.Journal of oncology · 2009Article
- PPAR Ligands for Cancer Chemoprevention.PPAR research · 2008Article
- Combination Therapy of PPARgamma Ligands and Inhibitors of Arachidonic Acid in Lung Cancer.PPAR research · 2008Article
- The Role of PPARgamma Receptors and Leukotriene B(4) Receptors in Mediating the Effects of LY293111 in Pancreatic Cancer.PPAR research · 2008Article
- Clinical Use of PPARgamma Ligands in Cancer.PPAR research · 2008Article
- PPARgamma and MEK Interactions in Cancer.PPAR research · 2008Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundLY293111 is an oral agent known to be a leukotriene B4 (LTB4) receptor antagonist and a 5-lipoxygenase inhibitor resulting in selective inhibition of the lipoxygenase pathway. Lipoxygenases metabolize arachidonic acid and have been involved in cancer cell proliferation and survival. In addition, LY293111 has been found to be a peroxisome proliferator activated receptor-gamma (PPAR-gamma) agonist. Antineoplastic activity of LY293111 has been identified in preclinical models both alone and in combination with chemotherapy agents including irinotecan. The NCIC Clinical Trials Group studied LY293111 in combination with irinotecan to determine the recommended dose of the combination and to describe its tolerability and pharmacokinetic interaction. In addition the anti-tumour activity of LY293111 in combination with irinotecan was documented. PATIENTS AND
methodsTwenty-eight patients with advanced solid tumours were treated on seven dose levels with the combination of irinotecan and LY293111. Irinotecan was administered intravenously every 21-days as a single dose. LY293111 was administered twice daily continuously by mouth.
resultsDose limiting toxicity (DLT) of grade 3 diarrhea was seen in two patients with doses of irinotecan 300 mg/m(2) IV every 21-days in combination with LY293111 300 mg BID. Subsequently the dose of irinotecan was decreased to 250 mg/m(2) IV every 21-days with escalating doses of LY293111. A DLT of grade 3 abdominal pain was seen at dose 600 mg BID of LY293111 with irinotecan 250 mg/m(2). The pharmacokinetics (PK) indicated that the administration of LY293111 did not have an effect on the PK of irinotecan or its metabolite SN-38. No responses were seen; seven patients had stable disease of a median duration of 4.4 months (range 2.8-13 months).
conclusionThe recommended phase II dose of LY293111 is 600 mg orally BID in combination with irinotecan 250 mg/m(2) IV every 21-days. Gastrointestinal adverse effects were common but could be well managed.
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