Randomized phase II study of bortezomib alone and bortezomib in combination with docetaxel in previously treated advanced non-small-cell lung cancer.
OBJECTIVE
To evaluate the efficacy and toxicity of bortezomib +/- docetaxel as second-line therapy in patients with relapsed or refractory advanced non-small-cell lung cancer (NSCLC).


METHODS
Patients were randomly assigned to bortezomib 1.5 mg/m2 (arm A) or bortezomib 1.3 mg/m2 plus docetaxel 75 mg/m2 (arm B). A treatment cycle of 21 days comprised four bortezomib doses on days 1, 4, 8, and 11, plus, in arm B, docetaxel on day 1. Patients could receive unlimited cycles. The primary end point was response rate.


RESULTS
A total of 155 patients were treated, 75 in arm A and 80 in arm B. Baseline characteristics were comparable. Investigator-assessed response rates were 8% in arm A and 9% in arm B. Disease control rates were 29% in arm A and 54% in arm B. Median time to progression was 1.5 months in arm A and 4.0 months in arm B. One-year survival was 39% and 33%, and median survival was 7.4 and 7.8 months in arms A and B, respectively. Adverse effect profiles were as expected in both arms, with no significant additivity. The most common grade > or = 3 adverse events were neutropenia, fatigue, and dyspnea (4% and 53%, 19% and 26%, and 17% and 14% of patients in arms A and B, respectively).


CONCLUSIONS
Bortezomib has modest single-agent activity in patients with relapsed or refractory advanced NSCLC using this schedule, with minor enhancement in combination with docetaxel. Additional investigation of bortezomib in NSCLC is warranted in combination with other drugs known to be active, or using different schedules.
Fanucchi
Michael P
MP
Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, USA.
Fossella
Frank V
FV
Belt
Robert
R
Natale
Ronald
R
Fidias
Panos
P
Carbone
David P
DP
Govindan
Ramaswamy
R
Raez
Luis E
LE
Robert
Francisco
F
Ribeiro
Maria
M
Akerley
Wallace
W
Kelly
Karen
K
Limentani
Steven A
SA
Crawford
Jeffrey
J
Reimers
Hans-Joachim
HJ
Axelrod
Rita
R
Kashala
Oscar
O
Sheng
Shihong
S
Schiller
Joan H
JH
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001897:Boronic Acids / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000069286:Bortezomib; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D000077143:Docetaxel; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D011719:Pyrazines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome; D014481:United States
D001897:Boronic Acids; D011719:Pyrazines; D043823:Taxoids; D000077143:Docetaxel; D000069286:Bortezomib