Phase 1-2a multicenter dose-ranging study of canfosfamide in combination with carboplatin and paclitaxel as first-line therapy for patients with advanced non-small cell lung cancer.
BACKGROUND
We aimed to evaluate the safety and efficacy of canfosfamide in combination with carboplatin and paclitaxel as first-line therapy in patients with locally advanced or metastatic non-small cell lung cancer.


METHODS
This was a phase 1-2a, multicenter, dose-ranging trial that enrolled patients with stage IIIB or IV non-small cell lung cancer with measurable disease. Patients received canfosfamide in doses ranging from 400 to 1000 mg/m2 intravenously (IV) with carboplatin at area under the curve 6 IV and paclitaxel at 200 mg/m2 IV day 1 every 3 weeks. The primary end point was objective response rate, and the secondary endpoints were safety and progression-free survival.


RESULTS
One hundred twenty-nine patients were treated with canfosfamide at dose levels of 400 (n = 3), 500 (n = 51), 750 (n = 54), and 1000 mg/m2 (n = 21). Objective tumor responses by RECIST were observed in 40 patients [34% (95% confidence interval [CI], 26-44)], the median progression-free survival was 4.3 months (95% CI, 3.7-5.2) and the median survival 9.9 months (95% CI, 7.7-11.9). The percent of patients alive at 1 year was 43.1%. The overall safety profile of the combination was acceptable and consistent with the profiles of the individual agents. In an exploratory analysis, patients receiving the optional maintenance canfosfamide therapy had a prolonged median survival of 16.8 months compared with those eligible for but not receiving maintenance therapy at 8.8 months (hazard ratio = 0.38, p < 0.001).


CONCLUSIONS
The combination of canfosfamide with carboplatin and paclitaxel chemotherapy is well tolerated and active. Maintenance canfosfamide may further improve outcomes. This regimen is worthy of additional study.
Sequist
Lecia V
LV
Massachusetts General Hospital Cancer Center, Boston, Massachusetts 02114, USA. lvsequist@partners.org
Fidias
Panos M
PM
Temel
Jennifer S
JS
Kolevska
Tatjana
T
Rabin
Michael S
MS
Boccia
Ralph V
RV
Burris
Howard A
HA
Belt
Robert J
RJ
Huberman
Mark S
MS
Melnyk
Ostap
O
Mills
Glenn M
GM
Englund
Craig W
CW
Caldwell
David C
DC
Keck
James G
JG
Meng
Lisa
L
Jones
Marsha
M
Brown
Gail L
GL
Edelman
Martin J
MJ
Lynch
Thomas J
TJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D016190:Carboplatin / Q000008:administration & dosage*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D003603:Cytotoxins; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D005978:Glutathione / Q000008:administration & dosage / Q000031:analogs & derivatives*; D006801:Humans; D007275:Injections, Intravenous; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage*; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D003603:Cytotoxins; C107479:TER 286; D016190:Carboplatin; D005978:Glutathione; D017239:Paclitaxel