In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 4_suppl ( 2012-02-01), p. 448-448
Abstract:
448 Background: EZN-2208 is a water-soluble, parenterally-delivered PEGylated conjugate of SN38 that increases solubility, exposure, and apparent half-life of SN-38. Methods: Patients with metastatic or locally recurrent CRC previously treated with fluoropyrimidines, oxaliplatin and irinotecan, and no more than 2 distinct progressions, were screened for K-Ras mutation and stratified accordingly. Patients with K-Ras tumor mutation (Mut) were treated with EZN-2208 (9mg/m 2 SN-38 equivalents) over 1-h IV on days 1, 8, 15 in 4-wk cycles (Arm A). Patients with K-Ras wild type (WT) tumors were randomized (2:1) to EZN-2208 (as above) and cetuximab (250mg/m 2 weekly following 400mg/m 2 on D1) (Arm B) or to irinotecan (125mg/m 2 ) over 90min IV days 1, 8 in 3 week cycles and cetuximab (as above) (Arm C). The primary objectives of the study were to determine the overall response rates (ORR) and progression free survival (PFS) (Arm A) and compare PFS (Arms B and C). A comparison of safety and toxicity of EZN-2208 and irinotecan was planned as well. Results: Demographic and efficacy parameters are summarized in the table . Common adverse events (Arms A%, B%, C%), observed in 〉 25% of patients in at least one arm of the study, were diarrhea (45%, 64%, 55%), fatigue (56%, 56%, 39%), nausea (43%, 59%, 47%), vomiting (31%, 46%, 39%), constipation (27%, 26%, 37%), abdominal pain (25%, 28%, 32%), anemia (33%, 21%, 21%), dermatitis acneiform (0%, 28%, 26%), hypokalemia (17%, 28%, 26%), and alopecia (12%, 28%, 3%). Conclusions: EZN-2208 in combination with cetuximab is active in patients in the 3rd line setting of CRC and comparable to irinotecan in combination with cetuximab. EZN-2208 monotherapy did not result in responses in patients with CRC following progression on irinotecan. EZN-2208 has an acceptable safety and tolerability profile as monotherapy, and in combination with cetuximab. [Table: see text]
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/jco.2012.30.4_suppl.448
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2012
detail.hit.zdb_id:
2005181-5
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