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PI‐16
Author(s) -
Reddy N. J.,
Beelen A. P.,
Perez R. P.,
Pipas M. J.,
Mackay K.,
Cole B. F.,
Salikova A. Y.,
Babich J. W.,
Abraham E. H.,
Lewis L. D.
Publication year - 2006
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2005.12.037
Subject(s) - medicine , cmax , tolerability , toxicity , pharmacokinetics , cachexia , asymptomatic , cancer , gastroenterology , adverse effect , anesthesia
BACKGROUND ATP is an endogenous nucleotide. Preliminary data suggested that exogenous ATP may improve cachexia in advanced cancer patients. The major objectives of this study were to determine the tolerable dose of a weekly infusion of ATP, within the planned dose range and to investigate its effects cancer cachexia biomarkers. METHODS This study was an open label intra‐patient dose escalation study. Cancer patients with advanced stage solid tumors received an 8 hour iv infusion of ATP weekly for 8 weeks at a starting dose of 50 mcg/kg/min, escalating to 75 and then 100 mcg/kg/min, if tolerated. Clinical and laboratory toxicity, ATP pharmacokinetics and biomarkers for cachexia were monitored. RESULTS Fifteen (9M:6F) pts. median age 63y (range 38–80) entered the study. ATP was tolerated by 15/15 pts. at 50 mcg/kg/min and by 12/12 pts. who received 100 mcg/kg/min. No patient developed grade III/IV dose limiting toxicity. Common toxicities were chest tightness/dyspnea, without EKG changes (60%); sinus tachycardia (40%) and were more frequent at the highest ATP dose. Two patients had transient, asymptomatic 3 rd degree AV block (grade I). ATP C max increased post infusion (ANOVA p =.01). Karnofsky score, weight, percent body fat, muscle strength and prealbumin concentration decreased (all p< 0.05) and CRP, IL‐6 increased (p< 0.05) with treatment. CONCLUSIONS In this Phase I study the tolerated ATP dose was 100 mcg/kg/min for 8h / week, and the biomarkers for cancer cachexia did not improve with treatment. Clinical Pharmacology & Therapeutics (2005) 79 , P11–P11; doi: 10.1016/j.clpt.2005.12.037