 Safety, tolerability and symptom outcomes associated with l-carnitine supplementation in patients with cancer, fatigue, and carnitine deficiency: A phase I/II study 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. |
| Department of Pain Medicine and Palliative Care Beth Israel Medical Center, New York City ©2005 Continuum Health Partners, Inc. www.stoppain.org/palliative_care |
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