A phase II study of cediranib as palliative treatment in patients with symptomatic malignant ascites or pleural effusion.
Malignant ascites and pleural effusion are challenging clinical problems, with a major impact on quality of life. We conducted a randomized phase II trial to assess the palliative value of cediranib, an oral vascular endothelial growth factor tyrosine kinase inhibitor (VEGF TKI). After a baseline paracentesis or thoracentesis (on day 0), patients with symptomatic malignant ascites and/or pleural effusion were randomized between immediate treatment with cediranib (Immediate Cediranib) or delayed treatment with cediranib (Delayed Cediranib) on day 29, or after a new puncture was needed. The primary objective of the study was the puncture-free survival, defined as the time from study start (day 1) to the first need for paracentesis or thoracentesis, or time to death, whichever event occurred first. Twelve patients were enrolled. The median puncture-free survival was 45 days (range 10-368) in the Immediate Cediranib patients and 7 days (range 4-13) in the Delayed Cediranib patients (P = 0.011). The change in puncture-free interval (the puncture-free survival after study start minus the puncture-free interval before study start) increased with a median of 31 days in the Immediate Cediranib patients and shortened with a median of 3 days in the Delayed Cediranib patients (P = 0.015). The most common adverse events were fatigue and anorexia. In conclusion, cediranib increased the puncture-free survival and puncture-free interval with an acceptable toxicity profile. This is the first study in which an oral VEGFR TKI showed beneficial palliative effects in patients with malignant effusions.
Department of Medical Oncology 452, Radboud University Medical Centre, PO Box 9101, 6500 HB, Nijmegen, The Netherlands, Sasja.Mulder@radboudumc.nl.
S F
SF
Mulder
M J
MJ
Boers-Sonderen
H F M
HF
van der Heijden
K C P
KC
Vissers
C J A
CJ
Punt
C M L
CM
van Herpen
D000284:Administration, Oral; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage; D001201:Ascites / Q000188:drug therapy*; D018450:Disease Progression; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010166:Palliative Care / Q000379:methods*; D019152:Paracentesis; D010996:Pleural Effusion / Q000188:drug therapy*; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage*; D011788:Quality of Life; D011799:Quinazolines / Q000008:administration & dosage*; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors; D013997:Time Factors; D016896:Treatment Outcome; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000037:antagonists & inhibitors; D007211:Indoles
D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D040262:Receptors, Vascular Endothelial Growth Factor; D040281:Vascular Endothelial Growth Factor Receptor-1; C500926:cediranib; D007211:Indoles