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Carnitine deficiency is among the many metabolic disturbances that may contribute
to fatigue in patients with cancer. Administration of l-carnitine may hold promise
as a treatment for this common symptom. Little is known about l-carnitine safety,
tolerability, and dose-response in patients with cancer.
The researchers conducted a Phase I/II open-label trial to assess the safety
and tolerability of l-carnitine supplementation and clarify the safe dose range
associated with symptom effects for future studies. Adult patients with advanced
cancer, carnitine deficiency, moderate to severe fatigue, and a Karnofsky Performance
Status (KPS) score >/=50 were entered by groups of at least three into a
standard maximum tolerated dose design. Each successive group received a higher
dose of l-carnitine (250, 750, 1250, 1750, 2250, 2750, 3000mg/day, respectively),
administered in two daily doses for 7 days. To compare symptom outcomes before
and after supplementation, patients completed validated measures of fatigue
(Brief Fatigue Inventory [BFI]), depressed mood (Center for Epidemiologic Studies
Depression Scale [CES-D]), quality of sleep (Epworth Sleeplessness Scale [ESS]),
and KPS at baseline and 1 week later. Of the 38 patients screened for carnitine
levels, 29 were deficient (76%). Twenty-seven patients participated (17 males,
10 females), and 21 completed the study; 17 of these patients had increased
carnitine levels at the end of the supplementation period. The highest dose
given was 3000mg/day. No patient experienced significant side effects, and no
toxicities were noted. Analysis of all the patients accrued showed a total carnitine
increase from 32.8+/-10 to 54.3+/-23muM/L and free carnitine increase from 26.8+/-8
to 44.1+/-17muM/L. Fatigue decreased significantly, as well as sleeplessness
and depression. A separate analysis of the 17 "responders" showed
a dose-response relationship for total-, free-carnitine levels and fatigue scores.
These findings suggest that l-carnitine may be safely administered at doses
up to 3000mg/day and that positive effects may be more likely at relatively
higher doses in this range. This study provides the basis for the design of
future placebo-controlled studies of l-carnitine supplementation for cancer-related
fatigue. Cruciani RA, Dvorkin E, Homel P, Malamud S, Culliney B, Lapin J, Portenoy
RK, Esteban-Cruciani N. Adapted from J
Pain Symptom Manage. J Pain Symptom Manage. 2006 Dec;32(6):551-559.
PMID 17157757
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=pubmed
Credit: PubMed, developed by the National Center for Biotechnology Information
(NCBI) at the
National Library of Medicine (NLM).
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