{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T12:48:33Z","timestamp":1790513313807,"version":"4.1.0"},"reference-count":17,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"31","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCO"],"published-print":{"date-parts":[[2005,11,1]]},"abstract":"<jats:sec><jats:title>Purpose<\/jats:title><jats:p> To establish the safety, pharmacokinetic parameters, maximum-tolerated dose, and recommended dose of aplidine, a novel marine cyclodepsipeptide, in patients with advanced cancer. <\/jats:p><\/jats:sec><jats:sec><jats:title>Patients and Methods<\/jats:title><jats:p> Using a modified Fibonacci method, we performed a phase I and pharmacokinetic study of aplidine administered as a 24-hour intravenous infusion every 2 weeks. <\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p> Sixty-seven patients received aplidine at a dose ranging from 0.2 to 8 mg\/m<jats:sup>2<\/jats:sup>. Dose-limiting myotoxicity corresponding to grade 2 to 3 creatine phosphokinase elevation and grade 1 to 2 myalgia and muscle weakness occurred in two of six patients at 6 mg\/m<jats:sup>2<\/jats:sup>. No cardiac toxicity was observed. Electron microscopy analysis showed the disappearance of thick filaments of myosin. Grade 3 muscle toxicity occurred in three of 14 patients at the recommended dose of 5 mg\/m<jats:sup>2<\/jats:sup> and seemed to be more readily reversible with oral carnitine (1 g\/10 kg). Therefore, dose escalation was resumed using carnitine prophylactically, allowing an increase in the recommended dose to 7 mg\/m<jats:sup>2<\/jats:sup>. Other toxicities were nausea and vomiting, diarrhea, asthenia, and transaminase elevation with mild hematologic toxicity. Aplidine displayed a long half-life (21 to 44 hours), low clearance (45 to 49 L\/h), and a high volume of distribution (1,036 to 1,124 L) with high interpatient variability in plasma, whereas in whole blood, clearance ranged from 3.0 to 6.2 L\/h. Minor responses and prolonged tumor stabilizations were observed in patients with medullary thyroid carcinoma. <\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p> Muscle toxicity was dose limiting in this study. Recommended doses of aplidine were 5 and 7 mg\/m<jats:sup>2<\/jats:sup> without and with carnitine, respectively. The role of carnitine will be further explored in phase II studies. <\/jats:p><\/jats:sec>","DOI":"10.1200\/jco.2005.09.357","type":"journal-article","created":{"date-parts":[[2005,9,20]],"date-time":"2005-09-20T00:34:09Z","timestamp":1127176449000},"page":"7871-7880","source":"Crossref","is-referenced-by-count":80,"title":["Phase I and Pharmacokinetic Study of Aplidine, a New Marine Cyclodepsipeptide in Patients With Advanced Malignancies"],"prefix":"10.1200","volume":"23","author":[{"given":"Sandrine","family":"Faivre","sequence":"first","affiliation":[{"name":"From the Department of Medicine, Institute Gustave-Roussy, Villejuif, France; and PharmaMar R&D, Colmenar Viejo, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"St\u00e9phanie","family":"Chi\u00e8ze","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Institute Gustave-Roussy, Villejuif, France; and PharmaMar R&D, Colmenar Viejo, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Delbaldo","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Institute Gustave-Roussy, Villejuif, France; and PharmaMar R&D, Colmenar Viejo, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nora","family":"Ady-vago","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Institute Gustave-Roussy, Villejuif, France; and PharmaMar R&D, Colmenar Viejo, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilia","family":"Guzman","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Institute Gustave-Roussy, Villejuif, France; and PharmaMar R&D, Colmenar Viejo, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis","family":"Lopez-Lazaro","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Institute Gustave-Roussy, Villejuif, France; and PharmaMar R&D, Colmenar Viejo, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"St\u00e9phanie","family":"Lozahic","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Institute Gustave-Roussy, Villejuif, France; and PharmaMar R&D, Colmenar Viejo, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9","family":"Jimeno","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Institute Gustave-Roussy, Villejuif, France; and PharmaMar R&D, Colmenar Viejo, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando","family":"Pico","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Institute Gustave-Roussy, Villejuif, France; and PharmaMar R&D, Colmenar Viejo, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean Pierre","family":"Armand","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Institute Gustave-Roussy, Villejuif, France; and PharmaMar R&D, Colmenar Viejo, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Antonio Lopez","family":"Martin","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Institute Gustave-Roussy, Villejuif, France; and PharmaMar R&D, Colmenar Viejo, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Raymond","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Institute Gustave-Roussy, Villejuif, France; and PharmaMar R&D, Colmenar Viejo, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"233","reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdg443"},{"key":"R2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00687325"},{"key":"R3","unstructured":"Forman AD, Shin DM, Jackson R: Myotonia in patients treated for cancer with didemnin B. 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