Abstract | PURPOSE: PATIENTS AND METHODS: Thirty-eight patients with advanced solid tumors were treated at five dose levels (200 to 800 mg BID) for a total of 102 cycles. RESULTS: The most common toxicity was diarrhea (76%). One patient at 600 mg BID (n = 11) and two at 800 mg BID (n = 8), experienced dose-limiting grade 3 diarrhea. Dose reductions and/or delays were infrequent. Increases in steady-state maximum plasma concentration (Cmax,ss) and area under the steady-state plasma concentration time curve 0 to 12 hours (AUCtau,ss) on day 8 could be considered to be dose-proportional over the four-fold-dose range. Interpatient variability in Cmax,ss and AUCtau,ss was estimated to be 65% and 71% respectively. There was a small increase in AUC (1.37; 90% CI, 0.85 to 2.21) between single and multiple doses. Two patients with progressive chondrosarcoma and melanoma had stable disease lasting approximately 336 and 168 days, respectively. CONCLUSION:
LY293111 can be administered safely by continuous oral therapy with mild toxicities. Diarrhea is dose-limiting. The recommended phase II dose will be 600 mg BID. The steady-state concentrations in humans exceed relevant levels observed in preclinical models.
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Authors | Gary K Schwartz, Aaron Weitzman, Eileen O'Reilly, Les Brail, Dinesh P de Alwis, Ann Cleverly, Barbara Barile-Thiem, Vincent Vinciguerra, Daniel R Budman |
Journal | Journal of clinical oncology : official journal of the American Society of Clinical Oncology
(J Clin Oncol)
Vol. 23
Issue 23
Pg. 5365-73
(Aug 10 2005)
ISSN: 0732-183X [Print] United States |
PMID | 15939925
(Publication Type: Clinical Trial, Clinical Trial, Phase I, Journal Article)
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Chemical References |
- Antineoplastic Agents
- Benzoates
- LY 293111
- Receptors, Leukotriene B4
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Topics |
- Administration, Oral
- Adult
- Aged
- Aged, 80 and over
- Antineoplastic Agents
(adverse effects, pharmacokinetics)
- Area Under Curve
- Benzoates
(adverse effects, pharmacokinetics)
- Female
- Humans
- Male
- Maximum Tolerated Dose
- Middle Aged
- Neoplasms
(metabolism)
- Receptors, Leukotriene B4
(antagonists & inhibitors)
- Safety
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