A pilot safety study of lenalidomide and radiotherapy for patients with newly diagnosed glioblastoma multiforme.
OBJECTIVE
To define the maximum tolerated dose (MTD) of lenalidomide, an analogue of thalidomide with enhanced immunomodulatory and antiangiogenic properties and a more favorable toxicity profile, in patients with newly diagnosed glioblastoma multiforme (GBM) when given concurrently with radiotherapy.


METHODS
Patients with newly diagnosed GBM received radiotherapy concurrently with lenalidomide given for 3 weeks followed by a 1-week rest period and continued lenalidomide until tumor progression or unacceptable toxicity. Dose escalation occurred in groups of 6. Determination of the MTD was based on toxicities during the first 12 weeks of therapy. The primary endpoint was toxicity.


RESULTS
Twenty-three patients were enrolled, of whom 20 were treated and evaluable for both toxicity and tumor response and 2 were evaluable for toxicity only. Common toxicities included venous thromboembolic disease, fatigue, and nausea. Dose-limiting toxicities were eosinophilic pneumonitis and transaminase elevations. The MTD for lenalidomide was determined to be 15 mg/m(2)/d.


CONCLUSIONS
The recommended dose for lenalidomide with radiotherapy is 15 mg/m(2)/d for 3 weeks followed by a 1-week rest period. Venous thromboembolic complications occurred in 4 patients, and prophylactic anticoagulation should be considered.
Center for Neuro-Oncology, Dana Farber/Brigham & Women's Cancer Center, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Jan
J
Drappatz
Eric T
ET
Wong
David
D
Schiff
Santosh
S
Kesari
Tracy T
TT
Batchelor
Lisa
L
Doherty
Debra Conrad
DC
Lafrankie
Naren
N
Ramakrishna
Stephanie
S
Weiss
Sharon T
ST
Smith
Abigail
A
Ciampa
Jennifer
J
Zimmerman
Louis
L
Ostrowsky
Karly
K
David
Andrew
A
Norden
Loretta
L
Barron
Christine
C
Sceppa
Peter M
PM
Black
Patrick Y
PY
Wen
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy* / Q000532:radiotherapy*; D006801:Humans; D000077269:Lenalidomide; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D013792:Thalidomide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D013792:Thalidomide; D000077269:Lenalidomide