TY - JOUR
T1 - Phase I dose-escalation study of plitidepsin in combination with bevacizumab in patients with refractory solid tumors
AU - Aspeslagh, Sandrine
AU - Awada, Ahmad
AU - Matos-Pita, Arturo S.
AU - Aftimos, Philippe
AU - Bahleda, Ratislav
AU - Varga, Andréa
AU - Soria, Jean Charles
N1 - Publisher Copyright:
© 2016 Wolters Kluwer Health, Inc.
PY - 2016/11/1
Y1 - 2016/11/1
N2 - This phase I trial evaluated the toxicity profile and maximum tolerated dose of the combination between the marine derived cyclodepsipeptide plitidepsin and bevacizumab in advanced cancer patients. Thirteen patients were enrolled and treated with plitidepsin at three dose levels (2.8 mg/m2, n=3; 3.8 mg/m2, n=4; and 4.8 mg/m2, n=6) with a fixed dose of bevacizumab (10 mg/kg). Both agents were administered intravenously at D1 and D15 of a 28-day cycle. All 13 patients were evaluable for safety and toxicity. Doselimiting toxicities occurred in two out of six patients treated at the maximum dose tested (plitidepsin 4.8 mg/m2 and bevacizumab 10 mg/kg) and consisted of grade 3 fatigue, grade 3 myalgia, and two grade 2/3 alanine aminotransferase increases lasting for more than 7 days or leading to subsequent cycle delay greater than 2 weeks (n=1 each). The recommended dose for the combination of plitidepsin with bevacizumab was 3.8 mg/m2 for plitidepsin and 10 mg/kg for bevacizumab every 2 weeks. Most frequent treatment-related adverse events were nausea, vomiting, fatigue, epistaxis, and headache. Relevant hematological toxicity was minimal. Objective disease responses were not observed; however, stable disease (>3 months) was observed in four patients with colorectal cancer, renal cancer, and cervical cancer. Combining plitidepsin with bevacizumab combination is feasible. Stable disease was the best response obtained.
AB - This phase I trial evaluated the toxicity profile and maximum tolerated dose of the combination between the marine derived cyclodepsipeptide plitidepsin and bevacizumab in advanced cancer patients. Thirteen patients were enrolled and treated with plitidepsin at three dose levels (2.8 mg/m2, n=3; 3.8 mg/m2, n=4; and 4.8 mg/m2, n=6) with a fixed dose of bevacizumab (10 mg/kg). Both agents were administered intravenously at D1 and D15 of a 28-day cycle. All 13 patients were evaluable for safety and toxicity. Doselimiting toxicities occurred in two out of six patients treated at the maximum dose tested (plitidepsin 4.8 mg/m2 and bevacizumab 10 mg/kg) and consisted of grade 3 fatigue, grade 3 myalgia, and two grade 2/3 alanine aminotransferase increases lasting for more than 7 days or leading to subsequent cycle delay greater than 2 weeks (n=1 each). The recommended dose for the combination of plitidepsin with bevacizumab was 3.8 mg/m2 for plitidepsin and 10 mg/kg for bevacizumab every 2 weeks. Most frequent treatment-related adverse events were nausea, vomiting, fatigue, epistaxis, and headache. Relevant hematological toxicity was minimal. Objective disease responses were not observed; however, stable disease (>3 months) was observed in four patients with colorectal cancer, renal cancer, and cervical cancer. Combining plitidepsin with bevacizumab combination is feasible. Stable disease was the best response obtained.
KW - bevacizumab
KW - phase I
KW - plitidepsin
UR - http://www.scopus.com/inward/record.url?scp=84986191343&partnerID=8YFLogxK
U2 - 10.1097/CAD.0000000000000409
DO - 10.1097/CAD.0000000000000409
M3 - Article
C2 - 27610894
AN - SCOPUS:84986191343
SN - 0959-4973
VL - 27
SP - 1021
EP - 1027
JO - Anti-Cancer Drugs
JF - Anti-Cancer Drugs
IS - 10
ER -