Low rates of contralateral neck failure in unilaterally treated oropharyngeal squamous cell carcinoma with prospectively defined criteria of lateralization.

BACKGROUND: Unilateral radiotherapy (RT) of oropharyngeal carcinomas is accepted for patients with lateralized primary and low-volume nodal disease. Utilizing prospectively defined criteria of laterality and staging positron emission tomography (PET)/CT, we studied outcomes in patients with advanced-stage oropharyngeal cancer undergoing unilateral RT. METHODS: Thirty-seven patients with oropharyngeal tumors >1 cm from midline regardless of node status underwent unilateral RT and were followed prospectively. Patient characteristics: T1 = 11; T2 = 22; T3 = 4; N0 = 3; N1 = 9; N2a = 3; N2b = 21; and Nx = 1. Dosimetry were determined and weekly National Comprehensive Cancer Network (NCCN) distress thermometer data were collected. RESULTS: At median follow-up of 32 months, 3-year locoregional control, contralateral regional failure, distant metastasis-free survival, and disease-free survival were 96%, 0%, 7%, and 93%, respectively. CONCLUSION: Low rates of contralateral neck failure are demonstrated utilizing prospectively defined criteria for unilateral RT. The tolerances of contralateral organs are respected and patients report low to moderate levels of distress throughout treatment.

L-carnitine supplementation in patients with advanced cancer and carnitine deficiency: a double-blind, placebo-controlled study.

Carnitine deficiency is prevalent in populations with chronic illness, including cancer. In a recent open-label study, L-carnitine supplementation was well tolerated and appeared to improve fatigue and other outcomes in cancer patients. To further evaluate this finding, adult patients with advanced cancer, carnitine deficiency (free carnitine more than 35 micromol/L for males or less than 25 micromol/L for females, or acyl/free carnitine ratio of more than 0.4), moderate to severe fatigue, and a Karnofsky Performance Status (KPS) score of 50 or more, were randomly assigned to receive either L-carnitine (0.5 g/day for two days, followed by 1g/day for two days, and then 2g/day for 10 days) or placebo. This double-blind phase was followed by an open-label phase, during which all patients received L-carnitine supplementation for two weeks. Outcomes included the fatigue subscale of the Functional Assessment of Cancer Therapy-Anemia (FACT-An), the Linear Analog Scale Assessments (LASA), the Mini-Mental State Exam (MMSE), and the KPS. Twenty-nine patients (12 placebo, 17 L-carnitine) were included in the intent-to-treat (ITT) analysis. From baseline to the end of the double-blind phase, serum total and free L-carnitine increased from 32.9+/-3.8 to 56.6+/-20.5 (P=0.004), and from 22.9+/-19.4 to 45.3+/-17.2 (P=0.004), respectively, in the L-carnitine-treated group, and from 28.2+/-10.2 to 36.2+/-8.7 (P=ns), and from 22.6+/-7.9 to 28.7+/-8.6 (P=ns) in the placebo group, respectively. The planned ITT analysis revealed no significant improvement in any of the study's endpoints, and these negative findings were not different when data from two patients who did not adhere to the protocol were eliminated. However, an exploratory covariate analysis that excluded these two protocol violators and included outcome data from both the double-blind and open-label phases demonstrated significantly improved fatigue on the FACT-An fatigue subscale (P<0.03), and significantly improved FACT-An functional well-being subscale (P<0.03), and KPS (P<0.003), in the group that started with L-carnitine during the double-blind phase. These data do not support the conclusion that L-carnitine in the doses tested reverses cancer-related fatigue in carnitine-deficient patients. However, L-carnitine supplementation does increase L-carnitine serum levels, and the positive findings in an exploratory analysis justify a larger study to determine if this strategy could be of benefit for a subpopulation of cancer patients.

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 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.