Phase II study of weekly plitidepsin as second-line therapy for small cell lung cancer.

2.50
Hdl Handle:
http://hdl.handle.net/10541/69557
Title:
Phase II study of weekly plitidepsin as second-line therapy for small cell lung cancer.
Authors:
Eisen, Tim; Thatcher, Nick; Leyvraz, Serge; Miller, Wilson H; Couture, Felix; Lorigan, Paul C ( 0000-0002-8875-2164 ) ; Lüthi, François; Small, David; Tanovic, Adnan; O'Brien, M
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. PATIENTS AND 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. CONCLUSION: 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.
Affiliation:
Department of Oncology, Addenbrooke's Hospital, Cambridge CB2 0QQ, United Kingdom. tim.eisen@medschl.cam.ac.uk
Citation:
Phase II study of weekly plitidepsin as second-line therapy for small cell lung cancer. 2009, 64 (1):60-5 Lung Cancer
Journal:
Lung Cancer
Issue Date:
Apr-2009
URI:
http://hdl.handle.net/10541/69557
DOI:
10.1016/j.lungcan.2008.06.017
PubMed ID:
18692272
Type:
Article
Language:
en
ISSN:
0169-5002
Appears in Collections:
All Christie Publications ; Medical Oncology

Full metadata record

DC FieldValue Language
dc.contributor.authorEisen, Tim-
dc.contributor.authorThatcher, Nick-
dc.contributor.authorLeyvraz, Serge-
dc.contributor.authorMiller, Wilson H-
dc.contributor.authorCouture, Felix-
dc.contributor.authorLorigan, Paul C-
dc.contributor.authorLüthi, François-
dc.contributor.authorSmall, David-
dc.contributor.authorTanovic, Adnan-
dc.contributor.authorO'Brien, M-
dc.date.accessioned2009-06-02T12:02:34Z-
dc.date.available2009-06-02T12:02:34Z-
dc.date.issued2009-04-
dc.identifier.citationPhase II study of weekly plitidepsin as second-line therapy for small cell lung cancer. 2009, 64 (1):60-5 Lung Canceren
dc.identifier.issn0169-5002-
dc.identifier.pmid18692272-
dc.identifier.doi10.1016/j.lungcan.2008.06.017-
dc.identifier.urihttp://hdl.handle.net/10541/69557-
dc.description.abstractOBJECTIVE: 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. PATIENTS AND 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. CONCLUSION: 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.en
dc.language.isoenen
dc.subjectAdrenal Gland Canceren
dc.subjectBone Canceren
dc.subjectLiver Canceren
dc.subjectCancer Stagingen
dc.subjectSkin Canceren
dc.subject.meshAdrenal Gland Neoplasms-
dc.subject.meshAdult-
dc.subject.meshAged-
dc.subject.meshAntineoplastic Agents-
dc.subject.meshBone Neoplasms-
dc.subject.meshDepsipeptides-
dc.subject.meshFemale-
dc.subject.meshHumans-
dc.subject.meshInfusions, Intravenous-
dc.subject.meshLiver Neoplasms-
dc.subject.meshLung Neoplasms-
dc.subject.meshLymphatic Metastasis-
dc.subject.meshMale-
dc.subject.meshMaximum Tolerated Dose-
dc.subject.meshMiddle Aged-
dc.subject.meshNeoplasm Staging-
dc.subject.meshPrognosis-
dc.subject.meshSalvage Therapy-
dc.subject.meshSkin Neoplasms-
dc.subject.meshSmall Cell Lung Carcinoma-
dc.subject.meshSurvival Rate-
dc.subject.meshTreatment Outcome-
dc.titlePhase II study of weekly plitidepsin as second-line therapy for small cell lung cancer.en
dc.typeArticleen
dc.contributor.departmentDepartment of Oncology, Addenbrooke's Hospital, Cambridge CB2 0QQ, United Kingdom. tim.eisen@medschl.cam.ac.uken
dc.identifier.journalLung Canceren

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