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01.03.2016 | Original Article

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

verfasst von: Rabih Said, Yang Ye, David S. Hong, Aung Naing, Gerald Falchook, Siqing Fu, Jennifer J. Wheler, Sarina Piha-Paul, Apostolia-Maria Tsimberidou

Erschienen in: Cancer Chemotherapy and Pharmacology | Ausgabe 3/2016

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Abstract

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.

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Titel: Phase I clinical trial of lenalidomide in combination with 5-fluorouracil, leucovorin, and oxaliplatin in patients with advanced cancer
verfasst von: Rabih Said
Yang Ye
David S. Hong
Aung Naing
Gerald Falchook
Siqing Fu
Jennifer J. Wheler
Sarina Piha-Paul
Apostolia-Maria Tsimberidou
Publikationsdatum: 01.03.2016
Verlag: Springer Berlin Heidelberg
Erschienen in: Cancer Chemotherapy and Pharmacology / Ausgabe 3/2016
Print ISSN: 0344-5704
Elektronische ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-015-2952-z

Springer Medizin

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