5 research outputs found
Phase II Clinical and Pharmacokinetic Study of Plitidepsin 3-Hour Infusion Every Two Weeks Alone or with Dexamethasone in Relapsed and Refractory Multiple Myeloma
Purpose: This trial evaluated the antitumor activity and safety of the marine-derived cyclodepsipeptide
plitidepsin in patients with relapsed/refractory multiple myeloma.
Experimental Design: This was a prospective, multicenter, open-label, single-arm, phase II trial with
plitidepsin at 5 mg/m2 as a 3-hour i.v. infusion every two weeks. The protocol was amended to allow
patients with suboptimal response to single-agent plitidepsin to add 20 mg/day on days 1 to 4 of oral
dexamethasone every two weeks.
Results: Fifty-one patients started treatment with plitidepsin and 47 were evaluable for efficacy. The
overall response rate (complete response plus partial response plus minimal response) was 13% with
plitidepsin alone and 22% in the cohort of patients with the addition of dexamethasone (n = 19, 18
evaluable). Both plitidepsin alone and with dexamethasone were feasible and well tolerated. Anemia
(29%) and thrombocytopenia (18%) were the most frequent grade 3/4 hematologic toxicities. Fatigue
(16%), muscular toxicity (6%), and transient alanine aminotransferase/aspartate aminotransferase
(27%) and creatine phosphokinase (23%) increases were the most relevant nonhematologic side effects.
A prolonged plasma half-life was observed in responding patients as compared with nonresponding patients
(P = 0.009).
Conclusions: Single-agent plitidepsin has limited but reproducible activity in relapsed/refractory multiple
myeloma patients. Activity observed after dexamethasone addition merits further study. Both regimens
were well tolerated in this heavily pretreated population
Phase II Clinical and Pharmacokinetic Study of Plitidepsin 3-Hour Infusion Every Two Weeks Alone or with Dexamethasone in Relapsed and Refractory Multiple Myeloma
Purpose: This trial evaluated the antitumor activity and safety of the marine-derived cyclodepsipeptide
plitidepsin in patients with relapsed/refractory multiple myeloma.
Experimental Design: This was a prospective, multicenter, open-label, single-arm, phase II trial with
plitidepsin at 5 mg/m2 as a 3-hour i.v. infusion every two weeks. The protocol was amended to allow
patients with suboptimal response to single-agent plitidepsin to add 20 mg/day on days 1 to 4 of oral
dexamethasone every two weeks.
Results: Fifty-one patients started treatment with plitidepsin and 47 were evaluable for efficacy. The
overall response rate (complete response plus partial response plus minimal response) was 13% with
plitidepsin alone and 22% in the cohort of patients with the addition of dexamethasone (n = 19, 18
evaluable). Both plitidepsin alone and with dexamethasone were feasible and well tolerated. Anemia
(29%) and thrombocytopenia (18%) were the most frequent grade 3/4 hematologic toxicities. Fatigue
(16%), muscular toxicity (6%), and transient alanine aminotransferase/aspartate aminotransferase
(27%) and creatine phosphokinase (23%) increases were the most relevant nonhematologic side effects.
A prolonged plasma half-life was observed in responding patients as compared with nonresponding patients
(P = 0.009).
Conclusions: Single-agent plitidepsin has limited but reproducible activity in relapsed/refractory multiple
myeloma patients. Activity observed after dexamethasone addition merits further study. Both regimens
were well tolerated in this heavily pretreated population