title: Phase II study of weekly plitidepsin as second-line therapy for small cell lung cancer.
abstract: OBJECTIVE
  To evaluate the antitumor activity and safety profile of plitidepsin administered as a 1h weekly intravenous (i.v.) infusion of 3.2mg/m(2) to patients with small cell lung cancer (SCLC) who relapsed or progressed after one line of chemotherapy.
  
  
  METHODS
  This was a multicenter, open-label, single-arm, exploratory, phase II clinical trial. Treatment lasted until disease progression, unacceptable toxicity, patient refusal or treatment delay for >2 weeks. Objective response rate (primary efficacy endpoint) was evaluated according to response evaluation criteria in solid tumors (RECIST). The rate of stable disease (SD) lasting for at least 6 months and time-to-event variables were secondary endpoints of efficacy. Toxicity was assessed using National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 2.0.
  
  
  RESULTS
  Twenty pretreated SCLC patients (median age, 60 years) with extensive (n = 13) or limited-stage disease (n = 7) received a total of 24 treatment cycles (median, one cycle per patient; range, 1-2). Objective tumor responses were not observed and only one of the 17 evaluable patients had SD. With a median follow-up of 11.8 months, the progression-free survival and the median overall survival were 1.3 months and 4.8 months, respectively. The most troubling or common toxicities were fatigue, muscle weakness, lymphopenia, anemia (no patients showed neutropenia), and asymptomatic, non-cumulative increase of transaminases levels and alkaline phosphatase.
  
  
  CONCLUSIONS
  This clinical trial shows that a cycle of 1h weekly i.v. infusion of plitidepsin (3.2mg/m(2)) was generally well tolerated other than fatigue and muscle weakness in patients with pretreated SCLC. One patient died due to multi-organ failure. The absence of antitumor activity found here precludes further studies of this plitidepsin schedule as second-line single-agent treatment of SCLC.
authors.affiliation: Department of Oncology, Addenbrooke's Hospital, Cambridge CB2 0QQ, United Kingdom. tim.eisen@medschl.cam.ac.uk
authors.forename: Tim
authors.initials: T
authors.lastname: Eisen
authors.forename: Nick
authors.initials: N
authors.lastname: Thatcher
authors.forename: Serge
authors.initials: S
authors.lastname: Leyvraz
authors.forename: Wilson H
authors.initials: WH
authors.lastname: Miller
authors.forename: Felix
authors.initials: F
authors.lastname: Couture
authors.forename: Paul
authors.initials: P
authors.lastname: Lorigan
authors.forename: François
authors.initials: F
authors.lastname: Lüthi
authors.forename: David
authors.initials: D
authors.lastname: Small
authors.forename: Adnan
authors.initials: A
authors.lastname: Tanovic
authors.forename: Mary
authors.initials: M
authors.lastname: O'Brien
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000188:drug therapy / Q000556:secondary; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001859:Bone Neoplasms / Q000188:drug therapy / Q000556:secondary; D047630:Depsipeptides / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008113:Liver Neoplasms / Q000188:drug therapy / Q000556:secondary; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009367:Neoplasm Staging; D010456:Peptides, Cyclic; D011379:Prognosis; D016879:Salvage Therapy; D012878:Skin Neoplasms / Q000188:drug therapy / Q000556:secondary; D055752:Small Cell Lung Carcinoma / Q000188:drug therapy* / Q000556:secondary; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D047630:Depsipeptides; D010456:Peptides, Cyclic; C098980:plitidepsin