LE-SN38 for metastatic colorectal cancer after progression on oxaliplatin: Results of CALGB 80402.

4109 Background: In patients (pts) with metastatic colorectal cancer (mCRC) after first-line progression on 5-fluorouracil (5-FU), irinotecan (IRI) improves survival over best supportive care or additional 5-FU. IRI provides limited survival benefit, commonly causes asthenia and diarrhea, and rarely causes fatal toxicities related to dehydration and sepsis. LE-SN38 is a liposomal formulation of SN38, the active metabolite of IRI. LE-SN38 was formulated in an attempt to improve the therapeutic index of IRI by preserving clinical activity without increasing overall toxicities. This single arm, open label Phase II study assesses the response rate (RR) and toxicity profile of LE-SN38 in pts with mCRC. METHODS: Pts had histologically or cytologically confirmed mCRC, measurable disease, and received one prior 5- FU/oxaliplatin (but not IRI) regimen for metastatic disease. Pts had ECOG PS 0-1, normal bone marrow, hepatic, and renal function. UGT1A1 genotype status was determined prior to registration and pts were eligible if homozygous for wild-type UGT1A1*1 or heterozygous for UGT1A1*28. Pts received LE-SN38 35mg/m(2) IV over 90 min every 21 days until disease progression for a minimum of 2 cycles. Tumor assessment by imaging was done every 2 cycles. The primary endpoint of this trial was RR. A RR of 15%, comparable to that of irinotecan, was considered worthy of further study. RESULTS: 30 pts (16 males, 14 females) were enrolled and treated from 1/06-1/07. Median age was 50-59y. Toxicities included Grade 4: leukocytes (7%), neutrophils/granulocytes (7%). Grade 3: hemoglobin (3%), lymphopenia (3%), neutrophils/granulocytes (7%), prothrombin time (PT) (3%), nausea (3%), gastrointestinal obstruction (3%), vomiting (3%), pain (3%). There was no Grade 3-4 diarrhea. There were no complete (CR) or partial responses (PR), but 11 pts had stable disease (SD) observed. Median PFS was 1.58 months (95% CI: 1.51, 2 months) and median OS was 9.07 months (95%CI: 6.67, 11.27 months). CONCLUSIONS: LE-SN38 did not meet the prespecified activity criteria for OR and PFS. Although LE-SN38 is associated with an acceptable toxicity profile, this formulation, dose and schedule of LE-SN38 does not merit further evaluation in previously treated pts with mCRC. No significant financial relationships to disclose.

Duke Scholars

Author Donna Niedzwiecki Biostatistics & Bioinformatics, Division of Biostatistics