Phase II study of plitidepsin in pretreated patients with locally advanced or metastatic non-small cell lung cancer

Christian Peschel, Joerg T. Hartmann, Alexander Schmittel, Carsten Bokemeyer, Folker Schneller, Ulrich Keilholz, Dieter Buchheidt, Susana Millan, Miguel Ángel Izquierdo, Ralf Dieter Hofheinz

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


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 5 mg/m2, every 2 weeks, to patients with chemotherapy pretreated advanced non-small cell lung cancer (NSCLC). Patients and 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. Conclusion: This study shows that plitidepsin 3-h continuous i.v. infusion (5 mg/m2) 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.

Original languageEnglish
Pages (from-to)374-380
Number of pages7
JournalLung Cancer
Issue number3
StatePublished - Jun 2008


  • Cancer
  • Chemotherapy
  • Lung
  • Plitidepsin
  • Second-line


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