title: Phase I study of weekly kahalalide F as prolonged infusion in patients with advanced solid tumors.
abstract: OBJECTIVE
  Kahalalide F (KF) is a dehydroaminobutyric acid-containing peptide from marine origin with activity against several human malignant cell lines. This dose-escalating phase I clinical trial evaluated the maximum tolerated dose (MTD), and the recommended dose for further phase II studies (RD) of weekly KF given as a prolonged (3- to 24-h) intravenous (i.v.) infusion.
  
  
  METHODS
  Eligible patients with advanced solid tumors and adequate performance status, hematologic, renal, and hepatic function were recruited into this study.
  
  
  RESULTS
  A total of 106 patients were treated with KF at four different weekly schedules: 3-h (n = 40), 24-h (n = 59), and two transitional schedules [6-h (n = 4) and 12-h (n = 3)]. For the 3-h weekly schedule, the MTD was 1,200 μg/m² and the RD was 1,000 μg/m². For the 24-h weekly schedule, the MTD was reached (6,650 μg/m²), but the RD could not be confirmed. Asymptomatic and reversible grade 3/4 transaminase increase was the most common dose-limiting toxicity in both schedules. Fatigue, paresthesia, pruritus, nausea, vomiting, and rash were the most common KF-related adverse events. No major deviations from linearity were detected in the pharmacokinetic (PK) profiles of both schedules, which showed a narrow distribution and short body residence. Prolonged disease stabilization (≥3 months) occurred in eight patients: two with the 3-h schedule and six with the 24-h schedule.
  
  
  CONCLUSIONS
  Administration of KF as prolonged weekly infusion appears feasible, with 3-h and 24-h infusion times having an acceptable safety profile.
authors: Instituto Catalán de Oncología, Ctra. Gran Vía, 08907 s/n. L'Hospitalet de Llobregat, Barcelona, Spain. ramonsalazar@iconcologia.net
authors: R
authors: R
authors: Salazar
authors: H
authors: H
authors: Cortés-Funes
authors: E
authors: E
authors: Casado
authors: B
authors: B
authors: Pardo
authors: A
authors: A
authors: López-Martín
authors: C
authors: C
authors: Cuadra
authors: J
authors: J
authors: Tabernero
authors: C
authors: C
authors: Coronado
authors: M
authors: M
authors: García
authors: A
authors: A
authors: Soto Matos-Pita
authors: B
authors: B
authors: Miguel-Lillo
authors: M
authors: M
authors: Cullell-Young
authors: J L
authors: JL
authors: Iglesias Dios
authors: L
authors: L
authors: Paz-Ares
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000188:drug therapy / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury / Q000503:physiopathology / Q000517:prevention & control*; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000097:blood / Q000188:drug therapy / Q000378:metabolism; D047630:Depsipeptides / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D015507:Drugs, Investigational / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D005260:Female; D006801:Humans; D015994:Incidence; D007262:Infusions, Intravenous; D008175:Lung Neoplasms / Q000097:blood / Q000188:drug therapy / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D012720:Severity of Illness Index; D013030:Spain / Q000453:epidemiology
chemical_list: D000970:Antineoplastic Agents; D047630:Depsipeptides; D015507:Drugs, Investigational; C097897:kahalalide F