Cediranib in combination with various anticancer regimens: results of a phase I multi-cohort study.
BACKGROUND
Cediranib is a highly potent vascular endothelial growth factor (VEGF) signaling inhibitor of all three VEGF receptors. This phase I, single-center, dose-finding study was designed primarily to investigate the safety and pharmacokinetics (PK) of cediranib with various anticancer regimens in patients with advanced solid tumors.


METHODS
Oral cediranib 20, 30, and/or 45 mg/day was given in combination with standard mFOLFOX6; docetaxel; irinotecan; irinotecan and cetuximab; or pemetrexed. The novel study design allowed simultaneous evaluation of the safety and PK of these regimens with cediranib in one study. Secondary assessments included a preliminary evaluation of efficacy.


RESULTS
Fifty-nine patients received cediranib and were evaluable for safety. The most common adverse events across the study were fatigue and diarrhea (both n = 52). The most common CTC grade ≥ 3 adverse events were neutropenia (n = 19) and fatigue (n = 16). Cediranib did not appear to have a major effect on the PK profile of any chemotherapy agent tested. A preliminary assessment of efficacy showed that objective responses were achieved in some patients (n = 6) who had previously progressed on similar regimens without cediranib.


CONCLUSIONS
In this group of heavily pretreated patients, the study design permitted simultaneous assessment of multiple treatment arms. Treatment with cediranib and the various anticancer regimens was generally well tolerated, with no apparent PK interaction and preliminary evidence of antitumor activity.
Lorusso
Patricia
P
Karmanos Cancer Institute, Detroit, MI 48201, USA. lorussop@karmanos.org
Shields
Anthony F
AF
Gadgeel
Shirish
S
Vaishampayan
Ulka
U
Guthrie
Tina
T
Puchalski
Thomas
T
Xu
John
J
Liu
Qi
Q
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011799:Quinazolines / Q000008:administration & dosage; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors*; D016896:Treatment Outcome; D007211:Indoles
D011799:Quinazolines; D040262:Receptors, Vascular Endothelial Growth Factor; C500926:cediranib; D007211:Indoles