Multicenter phase II study of plitidepsin in patients with relapsed/refractory non-Hodgkin's lymphoma.
This phase II clinical trial evaluated the efficacy, safety and pharmacokinetics of plitidepsin 3.2 mg/m(2) administered as a 1-hour intravenous infusion weekly on days 1, 8 and 15 every 4 weeks in 67 adult patients with relapsed/refractory aggressive non-Hodgkin's lymphoma. Patients were divided into two cohorts: those with non-cutaneous peripheral T-cell lymphoma (n=34) and those with other lymphomas (n=33). Efficacy was evaluated using the International Working Group criteria (1999). Of the 29 evaluable patients with non-cutaneous peripheral T-cell lymphoma, six had a response (overall response rate 20.7%; 95% confidence interval, 8.0%-39.7%), including two complete responses and four partial responses. No responses occurred in the 30 evaluable patients with other lymphomas (including 27 B-cell lymphomas). The most common plitidepsin-related adverse events were nausea, fatigue and myalgia (grade 3 in <10% of cases). Severe laboratory abnormalities (lymphopenia, anemia, thrombocytopenia, and increased levels of transaminase and creatine phosphokinase) were transient and easily managed by plitidepsin dose adjustments. The pharmacokinetic profile did not differ from that previously reported in patients with solid tumors. In conclusion, plitidepsin monotherapy has clinical activity in relapsed/refractory T-cell lymphomas. Combinations of plitidepsin with other chemotherapeutic drugs deserve further evaluation in patients with non-cutaneous peripheral T-cell lymphoma. (clinicaltrials.gov identifier: NCT00884286).
Institut de Cancérologie Gustave Roussy, Villejuif, France. ribrag@igr.fr
Vincent
V
Ribrag
Dolores
D
Caballero
Christophe
C
Fermé
Emanuele
E
Zucca
Reyes
R
Arranz
Javier
J
Briones
Christian
C
Gisselbrecht
Gilles
G
Salles
Alessandro M
AM
Gianni
Henry
H
Gomez
Carmen
C
Kahatt
Claudia
C
Corrado
Sergio
S
Szyldergemajn
Sonia
S
Extremera
Bernardo
B
de Miguel
Martin
M
Cullell-Young
Franco
F
Cavalli
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D047630:Depsipeptides / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D010456:Peptides, Cyclic; D012008:Recurrence; D016896:Treatment Outcome; D047368:Tumor Burden / Q000187:drug effects; D055815:Young Adult
D000970:Antineoplastic Agents; D047630:Depsipeptides; D010456:Peptides, Cyclic; C098980:plitidepsin