TY - JOUR
T1 - Randomized phase 2 study of pegylated SN-38 (EZN-2208) or irinotecan plus cetuximab in patients with advanced colorectal cancer
AU - Garrett, Christopher R.
AU - Bekaii-Saab, Tanios S.
AU - Ryan, Theresa
AU - Fisher, George A.
AU - Clive, Sally
AU - Kavan, Petr
AU - Shacham-Shmueli, Einat
AU - Buchbinder, Aby
AU - Goldberg, Richard M.
PY - 2013/12/15
Y1 - 2013/12/15
N2 - BACKGROUND Irinotecan is cytotoxic in patients with advanced colorectal cancer (CRC). SN-38 (10-hydroxy-7-ethyl-camptothecin) is the active metabolite of irinotecan. Attachment of polyethylene glycol (PEG) polymer chains (pegylation) to SN-38 (EZN-2208) increases the solubility, exposure, and half-life of SN-38. Preclinical studies demonstrated superior in vitro efficacy of EZN-2208 when it was tested in irinotecan-refractory human CRC cell lines. METHODS Patients with metastatic or locally recurrent CRC who had previously received 5-flurouracil (5-FU), oxaliplatin, and irinotecan were assigned to receive EZN-2208 monotherapy (9 mg/m2 on days 1, 8, and 15 every 28 days for patients with KRAS-mutant tumors only [arm A]), and patients with KRAS wild-type tumors were randomized (2:1) to receive either EZN-2208 plus cetuximab (400 mg/m2 loading dose on day 1 followed by 250 mg/m2 weekly starting on day 8 [arm B]) or irinotecan 125 mg/m2 on days 1 and 8 every 21 days plus cetuximab at the same doses indicated above (arm C). RESULTS The overall response rate and progression-free survival were 0% and 1.8 months, respectively, in arm A; 10.7% and 4.9 months (95% confidence interval [CI], 3.2-5.8 months), respectively, in arm B; and 14.3% and 3.7 months (95% CI, 2.1-5.8 months), respectively, in arm C. EZN-2208 was well tolerated in combination with cetuximab. No statistically significant difference in survival was observed between arm B (9.8 months; 95% CI, 7.2-11.2 months) and arm C (9.1 months; 95% CI, 6.0-13.0 months). CONCLUSIONS EZN-2208, either as monotherapy or in combination with cetuximab, was well tolerated in patients with refractory CRC. Overall survival and progression-free survival were similar in the cetuximab plus irinotecan arm and the EZN-2208 arm.
AB - BACKGROUND Irinotecan is cytotoxic in patients with advanced colorectal cancer (CRC). SN-38 (10-hydroxy-7-ethyl-camptothecin) is the active metabolite of irinotecan. Attachment of polyethylene glycol (PEG) polymer chains (pegylation) to SN-38 (EZN-2208) increases the solubility, exposure, and half-life of SN-38. Preclinical studies demonstrated superior in vitro efficacy of EZN-2208 when it was tested in irinotecan-refractory human CRC cell lines. METHODS Patients with metastatic or locally recurrent CRC who had previously received 5-flurouracil (5-FU), oxaliplatin, and irinotecan were assigned to receive EZN-2208 monotherapy (9 mg/m2 on days 1, 8, and 15 every 28 days for patients with KRAS-mutant tumors only [arm A]), and patients with KRAS wild-type tumors were randomized (2:1) to receive either EZN-2208 plus cetuximab (400 mg/m2 loading dose on day 1 followed by 250 mg/m2 weekly starting on day 8 [arm B]) or irinotecan 125 mg/m2 on days 1 and 8 every 21 days plus cetuximab at the same doses indicated above (arm C). RESULTS The overall response rate and progression-free survival were 0% and 1.8 months, respectively, in arm A; 10.7% and 4.9 months (95% confidence interval [CI], 3.2-5.8 months), respectively, in arm B; and 14.3% and 3.7 months (95% CI, 2.1-5.8 months), respectively, in arm C. EZN-2208 was well tolerated in combination with cetuximab. No statistically significant difference in survival was observed between arm B (9.8 months; 95% CI, 7.2-11.2 months) and arm C (9.1 months; 95% CI, 6.0-13.0 months). CONCLUSIONS EZN-2208, either as monotherapy or in combination with cetuximab, was well tolerated in patients with refractory CRC. Overall survival and progression-free survival were similar in the cetuximab plus irinotecan arm and the EZN-2208 arm.
KW - EZN-2208
KW - SN-38
KW - colorectal cancer
KW - pegylated
KW - randomized phase 2
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UR - http://www.scopus.com/inward/citedby.url?scp=84889882607&partnerID=8YFLogxK
U2 - 10.1002/cncr.28358
DO - 10.1002/cncr.28358
M3 - Article
C2 - 24105075
AN - SCOPUS:84889882607
SN - 0008-543X
VL - 119
SP - 4223
EP - 4230
JO - Cancer
JF - Cancer
IS - 24
ER -