The purpose of this study was to determine dose-limiting toxicities and pharmacokinetics of imatinib in children with refractory or recurrent Philadelphia chromosome-positive (Ph(+)) leukemias. Oral imatinib was administered daily at dose levels ranging from 260 to 570 mg/m(2). Plasma pharmacokinetic studies were performed on days 1 and 8 of course 1. There were 31 children who received 479 courses of imatinib. The most common toxicities encountered, which occurred in less than 5% of courses, were grade 1 or 2 nausea, vomiting, fatigue, diarrhea, and reversible increases in serum transaminases. One patient at the 440-mg/m(2) dose level had dose-limiting weight gain. There were no other first-course dose-limiting toxicities. A maximum tolerated dosage was not defined. Among 12 chronic myeloid leukemia (CML) patients evaluable for cytogenetic response, 10 had a complete response and 1 had a partial response. Among 10 acute lymphoblastic leukemia (ALL) patients evaluable for morphologic response, 7 achieved an M1 and 1 achieved an M2 bone marrow. We observed marked interpatient variability in the pharmacokinetic parameters. In conclusion, we found that daily oral imatinib is well tolerated in children at doses ranging from 260 to 570 mg/m(2). Doses of 260 and 340 mg/m(2) provide systemic exposures similar to those of adults who are treated with daily doses of 400 and 600 mg, respectively.

Strength training and aerobic exercise have beneficial effects on pain in adults with fibromyalgia. However, the equivalence of strengthening and aerobic exercise has not been reported. The primary aim of this randomized equivalence trial involving patients with fibromyalgia admitted to an interdisciplinary pain treatment program was to test the hypothesis that strengthening (n=36) and aerobic (n=36) exercise have equivalent effects (95% confidence interval within an equivalence margin ± 8) on pain, as measured by the pain severity subscale of the Multidimensional Pain Inventory. Secondary aims included determining the effects of strengthening and aerobic exercise on peak Vo(2) uptake, leg strength, and pressure pain thresholds. In an intent-to-treat analysis, the mean (± standard deviation) pain severity scores for the strength and aerobic groups at study completion were 34.4 ± 11.5 and 37.6 ± 11.9, respectively. The group difference was -3.2 (95% confidence interval, -8.7 to 2.3), which was within the equivalence margin of Δ8. Significant improvements in pain severity (P<.001), peak Vo(2) (P<.001), strength (P<.001), and pain thresholds (P<.001) were observed from baseline to week 3 in the intent-to-treat analysis; however, patients in the aerobic group (mean change 2.0 ± 2.6 mL/kg/min) experienced greater gains (P<.013) in peak Vo(2) compared to the strength group (mean change 0.4 ± 2.6 mL/kg/min). Knowledge of the equivalence and physiological effects of exercise have important clinical implications that could allow practitioners to target exercise recommendations on the basis of comorbid medical conditions or patient preference for a particular type of exercise. This study found that strength and aerobic exercise had equivalent effects on reducing pain severity among patients with fibromyalgia.

BACKGROUND Children with hepatocellular carcinoma (HCC) were treated on a prospective, randomized trial and were then analyzed to determine whether children with the fibrolamellar (FL) histologic variant of HCC have a more favorable presentation, increased surgical resectability, greater response to therapy, and improved outcome compared with children who have typical HCC. METHODS Forty‐six patients were enrolled on Pediatric Intergroup Hepatoma Protocol INT‐0098 (Pediatric Oncology Group Study 8945/Children's Cancer Group Study 8881) between August 1989 and December 1992. After undergoing initial surgery or biopsy, children with Stage I HCC (n = 8 patients), Stage III HCC (n = 25 patients), and Stage IV HCC (n = 13 patients) were assigned randomly, regardless of histology, to receive treatment either with cisplatin, vincristine, and fluorouracil (n = 20 patients) or with cisplatin and continuous‐infusion doxorubicin (n = 26 patients). RESULTS Ten of 46 patients (22%) had the fibrolamellar variant of HCC (FL‐HCC). For the entire cohort, the estimated 5‐year event free survival (EFS) rate (± standard deviation) was 17% ± 6%. There was no difference in outcome among patients who were treated with either regimen. The 5‐year EFS rate for patients with FL‐HCC was no different the rate for patients with typical HCC (30% ± 15% vs. 14% ± 6%, respectively; P = 0.18), although the median survival was longer in patients with FL‐HCC. There was no difference in the number of patients with advanced‐stage disease, the incidence of surgical resectability at diagnosis, or the response to treatment between patients with FL‐HCC and patients with typical HCC. CONCLUSIONS Children with FL‐HCC do not have a favorable prognosis and do not respond any differently to current therapeutic regimens than patients with typical HCC. Children with initially resectable HCC have a good prognosis irrespective of histologic subtype, whereas outcomes are poor uniformly for children with advanced‐stage disease. The use of novel chemotherapeutic agents and the incorporation of other treatment modalities are indicated to improve the dismal survival of pediatric patients with all histologic variants of advanced‐stage HCC. Cancer 2003;97:2006–12. © 2003 American Cancer Society. DOI 10.1002/cncr.11292