Phase I clinical trial of lenalidomide in combination with 5-fluorouracil, leucovorin, and oxaliplatin in patients with advanced cancer.

PURPOSE

Lenalidomide has synergistic anticancer effects when used with chemotherapy. We conducted a phase I study of lenalidomide in combination with FOLFOX (5-fluorouracil, leucovorin, and oxaliplatin) in patients with advanced cancer.

METHODS

A "3 + 3" study design was used. Lenalidomide was given orally on days 1-14, oxaliplatin and leucovorin were given intravenously on day 1, and 5-fluorouracil was given as a continuous infusion on days 1-2. The dose escalation phase of the study was followed by an expansion phase. We assessed the maximum tolerated dose, dose-limiting toxicities, and response.

RESULTS

Thirty-eight patients were treated [median age 53 years (range 31-76); male/female 20:18]. The most common diagnosis was colorectal cancer (CRC) (n= 30, 79%). Overall, 132 cycles (median 2/patient) were administered. No dose-limiting toxicities were observed. The maximum tested dose (dose level 4) was used in the expansion phase. Grade 3/4 treatment-related toxicities (all reversible) were seen in 14 (37%) patients and included neutropenia (n = 11), thrombocytopenia (n = 2), and fatigue (n = 2). There were no thrombotic events. Response was evaluable in 32 patients: 19 (59%) had stable disease (SD), including SD ≥ 6 months in 4 (13%) patients. Tumor types with SD ≥ 6 months were CRC (n = 2; progression-free survival [PFS] 11.3 and 7.1 months, respectively), gastric (n = 1; PFS 8.5 months), and pancreatic (n = 1; PFS 6.4 months) cancer. The median PFS and overall survival durations were 2.2 months (range <1.3-23) and 5.5 months (range <1.6-23), respectively.

CONCLUSIONS

Lenalidomide in combination with FOLFOX was well tolerated. Four patients had prolonged stable disease. This combination merits further investigation for selected patient populations.