Phase II study of plitidepsin in pretreated patients with locally advanced or metastatic non-small cell lung cancer.
OBJECTIVE
To evaluate the progression-free rate (PFR) at 3 months (13+/-1 weeks), antitumor response, time-to-event efficacy endpoints, and toxicity profile of plitidepsin administered as a 3-h continuous i.v. infusion at a dose of 5mg/m(2), every 2 weeks, to patients with chemotherapy pretreated advanced non-small cell lung cancer (NSCLC).


METHODS
This was a multicenter, non-randomized, exploratory, phase II study. Treatment lasted until disease progression, unacceptable toxicity, patient refusal or treatment delay for >2 weeks. PFR (primary efficacy endpoint) and objective response rate (secondary efficacy endpoint) were evaluated according to RECIST, while the toxic profile of plitidepsin was assessed using the NCI-CTC, version 2.0.


RESULTS
A total of 21 patients with a median age of 61 years and with locally advanced or metastatic non-resectable NSCLC, who had previously received only one line of chemotherapy in an advanced setting, received a total of 54 cycles of treatment (median of two cycles per patient; range: 1-8). Antitumor activity was seen in 3 (1 PR, 2 SD) out of 17 evaluable patients according to RECIST. One patient was responder for the primary (PFR at 13+/-1 weeks) and secondary efficacy endpoint (stable disease according to RECIST). Other two patients were non-responders for the primary efficacy endpoint, but had stable disease (not confirmed at weeks 13+/-1 due to previous withdrawal due to adverse events). With a median follow-up of 12.3 months, the median time to progression (TTP) and the median overall survival (OS) were 1.2 months and 4.3 months, respectively. The incidence of plitidepsin-related toxicities was low and most of them were mild-to-moderate in severity. The most common side effects were anemia, and asymptomatic and non-cumulative increases of gamma-glutamyltransferase (GGT) and liver transaminase levels.


CONCLUSIONS
This study shows that plitidepsin 3-h continuous i.v. infusion (5mg/m(2)) every 2 weeks, was feasible and well tolerated in patients with pretreated NSCLC. The lack of evidence of antitumor activity precludes further studies with this plitidepsin schedule in this tumor setting.
Peschel
Christian
C
Technische Universität, III. Medizinische Klinik, München, Germany. christian.peschel@lrz.tu-muenchen.de
Hartmann
Joerg T
JT
Schmittel
Alexander
A
Bokemeyer
Carsten
C
Schneller
Folker
F
Keilholz
Ulrich
U
Buchheidt
Dieter
D
Millan
Susana
S
Izquierdo
Miguel Angel
MA
Hofheinz
Ralf-Dieter
RD
D000328:Adult; D000368:Aged; D000740:Anemia / Q000139:chemically induced; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000188:drug therapy* / Q000473:pathology*; D047630:Depsipeptides / Q000008:administration & dosage* / Q000009:adverse effects; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D010456:Peptides, Cyclic; D000637:Transaminases / Q000097:blood; D014561:Urochordata; D005723:gamma-Glutamyltransferase / Q000097:blood
D047630:Depsipeptides; D010456:Peptides, Cyclic; D005723:gamma-Glutamyltransferase; D000637:Transaminases; C098980:plitidepsin