Sargramostim in combination with irinotecan (I), 5-fluorouracil (F), and leucovorin (L) for metastatic colorectal cancer (CRC): Second interim results of PROGRESS trial

Abstract

3663 Background: Weekly/biweekly irinotecan-based regimens improve survival in CRC patients but are associated with significant myelosuppressive toxicities. In the PROGRESS trial, sargramostim (Leukine®, GM-CSF) was added to two commonly used regimens to study its ability to reduce toxicities and allow increased chemotherapy dose delivery thereby delaying disease progression. Methods: Weekly: Day 1: 125 mg/m2 I, 500 mg/m2 F, 20 mg/m2 L. Sargramostim 250 μg/m2 on Days 2–6. Cycles consist of 4 weekly courses + 2 weeks rest for up to 48 weeks. Biweekly: Day 1: 180 mg/m2 I, 1000 mg/m2 F, 200 mg/m2 L. Day 2: 400 mg/m2 F bolus, followed by 600 mg/m2 F infusion over 22 hr; 200 mg/m2 L. Sargramostim 250 μg/m2 on Days 4–13 for up to 48 weeks. The primary endpoint is progression-free survival (PFS) at 24 weeks (using χ2 test and null hypothesis that PFS ≤ 55%). Results: Eighty-one patients were enrolled, and 64 were evaluable for PFS. Of these, 51 (80%) had liver involvement, 20 (31%) had lung involvement, and 24 (38%) had prior F therapy. At 24 weeks, 38 patients (59%) had no disease progression, 26 (41%) had progressed, and 9 (14%) had died. Median time to progression was 215 days. Mean dose intensity was 83% of the planned I and F doses. Grade 3/4 events included diarrhea (28%), neutropenia (23%), deep vein thrombophlebitis (16%), dehydration (9%), asthenia (6%), vomiting (6%), and 4 infections (6%, 2 fever and 2 pneumonia). Only 1 patient had Grade 3 bone pain (Cycle 1). Conclusions: The addition of sargramostim to weekly/biweekly irinotecan-based regimens for CRC supports planned dose delivery by decreasing neutropenia and severe infections, and may improve PFS. Sargramostim is generally well tolerated with weekly and biweekly IFL regimens, and should be considered with other short-cycle chemotherapy regimens. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Berlex, Inc.