The integration of planned neck dissection into the multidisciplinary management of patients with locoregionally advanced SCCHN is highly effective in controlling cervical metastatic disease. Modified and selective neck dissection procedures can be performed in the majority of patients, regardless of the response in the neck subsequent to concomitant radiochemotherapy. We recommend a planned neck dissection(s) in all patients staged (pretreatment) with N2 or greater neck disease and in select N1 cases.

Carnitine deficiency is among the many metabolic disturbances that may contribute to fatigue in patients with cancer. Administration of exogenous 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. We conducted a Phase I/II open-label trial to assess the safety and tolerability of exogenous L-carnitine and clarify the safe dose range associated with symptom effects for future controlled trials. Adult patients with advanced cancer, carnitine deficiency (free carnitine <35 for males or <25 microM/L for females, or acyl/free carnitine ratio >0.4), moderate to severe fatigue, and a Karnofsky Performance Status (KPS) score > or =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, 3000 mg/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 ("intention to treat, ITT") (17 males, 10 females), and 21 completed the study ("completers"); 17 of these patients ("responders," mean+/-[SD] age=57.9+/-15) had increased carnitine levels at the end of the supplementation period. The highest dose achieved was 3000 mg/day. No patient experienced significant side effects and no toxicities were noted. Analysis of all the patients accrued (ITT, n=27) showed a total carnitine increase from 32.8+/-10 to 54.3+/-23 microM/L (P<0.001) and free carnitine increase from 26.8+/-8 to 44.1+/-17 microM/L (P<0.001). BFI decreased significantly, from 66+/-12 to 39.7+/-26 (P<0.001); ESS decreased from 12.9+/-12 to 9+/-6 (P=0.001); and CES-D decreased from 29.2+/-12 to 19+/-12 (P<0.001). A separate analysis of the 17 "responders" showed a dose-response relationship for total- (r=0.54, P=0.03), free-carnitine (r=0.56, P=0.02) levels, and fatigue (BFI) scores (r=-0.61, P=0.01). These findings suggest that l-carnitine may be safely administered at doses up to 3000 mg/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.

Nutritional factors are among the postulated causes of fatigue, a highly prevalent symptom in the cancer population, with serious impact on patients' quality of life. Deficiency of the micronutrient carnitine may play a role by reducing energy production through fatty acid oxidation. We present preliminary data of an open-label, dose-finding study to determine safety and maximally tolerated dose (MTD) of 1 week of L-carnitine supplementation in cancer patients with fatigue and carnitine deficiency. Patients who met inclusion/exclusion criteria underwent carnitine level determination. Eighty-three percent of these patients (15/18) had carnitine deficiency. Preliminary data analysis of 13 patients showed that total carnitine increased from 30.0 +/- 6.9 to 41.0 +/- 12.1 (mean +/- SD) after 1 week of supplementation (P = 0.01), and free carnitine increased from 24.3 +/- 6.1 to 33.8 +/- 9.8 (P = 0.004). Outcome measures were fatigue (BFI score), depression (CES-D), sleep disruption (ESS), and performance status (Karnofsky). Median (min, max) BFI score at baseline was 73 (46, 82) versus 50 (3, 82) after 1-week supplementation (P = 0.009). CES-D score at baseline was 29 (16, 42) and 22 (8, 32) after 1 week (P = 0.028). ESS at baseline was 46.5 (0, 69) and 30.4 (0, 72) after 1 week (P = 0.015). Karnofsky score did not change significantly (P = 0.38). We are currently conducting a randomized, double-blind, placebo-controlled study to rigorously assess the role of L-carnitine for the treatment of fatigue and depression in cancer patients.