title: Phase III, randomized, double-blind, placebo-controlled study of modafinil for fatigue in patients treated with docetaxel-based chemotherapy.
abstract: OBJECTIVE
  Modafinil has been reported to benefit a subgroup of patients suffering severe fatigue while undergoing chemotherapy. Docetaxel is associated with fatigue that may lead to premature therapy withdrawal. We investigated whether modafinil could reduce fatigue during docetaxel chemotherapy.
  
  
  METHODS
  This multicenter, randomized, double-blind, placebo-controlled study evaluated the efficacy of modafinil in patients with metastatic prostate or breast cancer undergoing docetaxel chemotherapy (every 21 days; minimum dose 50 mg/m(2)). At the start of their third or subsequent chemotherapy cycle, patients with significant docetaxel-associated fatigue were randomized to receive concurrent modafinil 200 mg/day or placebo for 15 days ("treatment periods" (TP)). Docetaxel was continued for up to four further cycles. Fatigue was evaluated with the fatigue component of the MD Anderson Symptom Inventory (MDASI). The primary endpoint was cumulative MDASI area under the curve (AUC) during the first 7 days of study medication during TP1 and TP2.
  
  
  RESULTS
  Evaluable data were available from 83 patients (65 with prostate cancer). There was no statistically significant difference between the two treatment arms for the primary endpoint (MSADI AUC3-10 35.9 vs 39.6; 95 % confidence interval -8.9, 1.4; P=0.15). Overall toxicity was comparable between treatment groups; however, the incidence of grade ≤ 2 nausea and vomiting was higher in the modafinil arm (45.4 vs 25 %).
  
  
  CONCLUSIONS
  Assessing and managing chemotherapy-related fatigue remains a major challenge. There was a lack of difference between the two arms in the planned primary endpoint. However, there was a modest but consistent trend towards improvement of docetaxel-related fatigue in those treated with modafinil. Based on the study findings, modafinil for the treatment of fatigue associated with docetaxel chemotherapy elicits modest improvements. Larger, longer term, randomized, controlled studies are required to clarify the exact role of modafinil in the treatment of docetaxel-related fatigue.
authors: Department of Medical Oncology, Prince of Wales Hospital, High Street, Randwick, New South Wales, 2031, Australia, elizabeth.hovey@sesiahs.health.nsw.gov.au.
authors: Elizabeth
authors: E
authors: Hovey
authors: Paul
authors: P
authors: de Souza
authors: Gavin
authors: G
authors: Marx
authors: Phillip
authors: P
authors: Parente
authors: Tal
authors: T
authors: Rapke
authors: Andrew
authors: A
authors: Hill
authors: Antonino
authors: A
authors: Bonaventura
authors: Antony
authors: A
authors: Michele
authors: Paul
authors: P
authors: Craft
authors: Ehtesham
authors: E
authors: Abdi
authors: Andrew
authors: A
authors: Lloyd
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D001559:Benzhydryl Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000077143:Docetaxel; D004311:Double-Blind Method; D005221:Fatigue / Q000139:chemically induced* / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077408:Modafinil; D009325:Nausea / Q000139:chemically induced; D009362:Neoplasm Metastasis; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects; D014839:Vomiting / Q000139:chemically induced; D064690:Wakefulness-Promoting Agents / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D001559:Benzhydryl Compounds; D043823:Taxoids; D064690:Wakefulness-Promoting Agents; D000077143:Docetaxel; D000077408:Modafinil