Impact of individualized treatment on recovery from fatigue and return to work in survivors of advanced-stage Hodgkin's lymphoma: results from the randomized international GHSG HD18 trial.

BACKGROUND: Persisting cancer-related fatigue impairs health-related quality of life (HRQoL) and social reintegration in patients with Hodgkin's lymphoma (HL). The GHSG HD18 trial established treatment de-escalation for advanced-stage HL guided by positron emission tomography after two cycles (PET-2) as new standard. Here, we investigate the impact of treatment de-escalation on long-term HRQoL, time to recovery from fatigue (TTR-F), and time to return to work (TTR-W). PATIENTS AND METHODS: Patients received European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30) and life situation questionnaires at baseline, interim, end of treatment, and yearly follow-up. TTR-F was defined as time from the end of chemotherapy until the first fatigue score <30. TTR-W was analyzed in previously working or studying patients and measured from the end of treatment until the first documented work or education. We compared duration of treatment on TTR-F and TTR-W using Cox proportional hazards regression adjusted for confounding variables. RESULTS: HRQoL questionnaires at baseline were available in 1632 (83.9%) of all randomized patients. Overall, higher baseline fatigue and age were significantly associated with longer TTR-F and TTR-W and male sex with shorter TTR-W. Treatment reduction from eight to four chemotherapy cycles led to a significantly shorter TTR-F [hazard ratio (HR) 1.41, P = 0.008] and descriptively shorter TTR-W (HR 1.24, P = 0.084) in PET-2-negative patients. Reduction from six to four cycles led to non-significant but plausible intermediate accelerations. The addition of rituximab caused significantly slower TTR-F (HR 0.70, P = 0.0163) and TTR-W (HR 0.64, P = 0.0017) in PET-2-positive patients. HRQoL at baseline and age were the main determinants of 2-year HRQoL. CONCLUSIONS: Individualized first-line treatment in patients with advanced-stage HL considerably shortens TTR-F and TTR-W in PET-2-negative patients. Our results support the use of response-adapted shortened treatment duration for patients with HL.

Steady-state plasma kinetics of slow-release propafenone, its two isomers and its main metabolites.

Steady-state plasma kinetics of propafenone (CAS 54063-53-5), the S- and R-enantiomers, and the two main metabolites were investigated in a double-blind, placebo-controlled dose-finding study using a slow-release formulation of propafenone at three different dose regimens (2 x 225 mg, 2 x 325 mg, and 2 x 425 mg). The study included a total of 24 patients (18 m, 6 f) with symptomatic ventricular arrhythmia. Since statistically valuable data was limited by a considerable portion of undetectable plasma concentrations among patients having received verum, kinetics could be followed up only in a group of 14 patients (10 m, 4 f) over a period of 12 h under steady state conditions. All patients were phenotyped prior to the study by measuring the ratio of sparteine/dehydrosparteine and three poor metabolizers were identified. A detailed description of the analytical methods used is given. With the low dose, a mean plasma level of 87 +/- 16 ng propafenone per ml plasma was obtained, with the medium dose a level of 243 +/- 34 ng/ml and with the higher dose 334 +/- 71 ng/ml were reached. All three doses of the slow-release preparation resulted in a smoothened and thus therapeutically favorable plasma concentration curve, independently from phenotype. With regard to the two propafenone enantiomers, a preferential clearance of the R-form (S/R = 2.08 +/- 0.19) could be confirmed without observing a change in the S/R ratio with time.