{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T11:45:51Z","timestamp":1790768751446,"version":"4.1.0"},"reference-count":25,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"13","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCO"],"published-print":{"date-parts":[[2007,5,1]]},"abstract":"<jats:sec><jats:title>Purpose<\/jats:title><jats:p> Imexon, a pro-oxidant small molecule, has antitumor activity in preclinical models. The drug induces apoptosis through accumulation of reactive oxygen species. The purpose of this trial was to define the maximum-tolerated dose (MTD), toxicities, pharmacokinetics, and pharmacodynamics of imexon in patients with advanced cancers. <\/jats:p><\/jats:sec><jats:sec><jats:title>Patients and Methods<\/jats:title><jats:p> Forty-nine patients with metastatic cancer received intravenous imexon over 30 to 45 minutes for 5 consecutive days (one course) every other week (days 1 through 5 and 15 through 19) monthly. Doses were initially escalated using an accelerated trial design and then a modified Fibonacci method. Plasma imexon levels and six different thiols were measured by high-performance liquid chromatography assays. <\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p> There were 13 dose levels evaluated, from 20 mg\/m<jats:sup>2<\/jats:sup>\/d to 1,000 mg\/m<jats:sup>2<\/jats:sup>\/d. The MTD recommended for phase II studies was 875 mg\/m<jats:sup>2<\/jats:sup>\/d for 5 days every 2 weeks (n = 9 patients). The two dose-limiting toxicities at 1,000 mg\/m<jats:sup>2<\/jats:sup>\/d involved grade 3 abdominal pain and fatigue and grade 4 neutropenia, which occurred in one patient each. Other common toxicities included nausea and vomiting (58%) and constipation (63%); both were managed well with prophylactic medications. One partial response was obtained in a heavily pretreated patient with non-Hodgkin's lymphoma. Pharmacokinetic studies showed dose-independent clearance, with a 95-minute mean half-life. Plasma thiol studies showed a dose- and area under the curve\u2013dependent decrease in cystine levels 8 hours after dosing at \u2265 750 mg\/m<jats:sup>2<\/jats:sup>\/d. <\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p> The phase II recommended dose of imexon is 875 mg\/m<jats:sup>2<\/jats:sup>\/d for 5 days every other week. A decrease in plasma thiols did correlate with imexon exposure. <\/jats:p><\/jats:sec>","DOI":"10.1200\/jco.2006.08.9672","type":"journal-article","created":{"date-parts":[[2007,4,30]],"date-time":"2007-04-30T22:28:58Z","timestamp":1177972138000},"page":"1779-1784","source":"Crossref","is-referenced-by-count":47,"title":["Phase I Trial of Imexon in Patients With Advanced Malignancy"],"prefix":"10.1200","volume":"25","author":[{"given":"Tomislav","family":"Dragovich","sequence":"first","affiliation":[{"name":"From the College of Medicine, Arizona Cancer Center, University of Arizona; Arizona Clinical Research Center; AmpliMed Corp, Tucson; Premiere Oncology, Scottsdale, AZ; Scott & White Clinic, Temple, TX; and The Angeles Clinic and Research Institute, Santa Monica, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Gordon","sequence":"additional","affiliation":[{"name":"From the College of Medicine, Arizona Cancer Center, University of Arizona; Arizona Clinical Research Center; AmpliMed Corp, Tucson; Premiere Oncology, Scottsdale, AZ; Scott & White Clinic, Temple, TX; and The Angeles Clinic and Research Institute, Santa Monica, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Mendelson","sequence":"additional","affiliation":[{"name":"From the College of Medicine, Arizona Cancer Center, University of Arizona; Arizona Clinical Research Center; AmpliMed Corp, Tucson; Premiere Oncology, Scottsdale, AZ; Scott & White Clinic, Temple, TX; and The Angeles Clinic and Research Institute, Santa Monica, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas","family":"Wong","sequence":"additional","affiliation":[{"name":"From the College of Medicine, Arizona Cancer Center, University of Arizona; Arizona Clinical Research Center; AmpliMed Corp, Tucson; Premiere Oncology, Scottsdale, AZ; Scott & White Clinic, Temple, TX; and The Angeles Clinic and Research Institute, Santa Monica, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Modiano","sequence":"additional","affiliation":[{"name":"From the College of Medicine, Arizona Cancer Center, University of Arizona; Arizona Clinical Research Center; AmpliMed Corp, Tucson; Premiere Oncology, Scottsdale, AZ; Scott & White Clinic, Temple, TX; and The Angeles Clinic and Research Institute, Santa Monica, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.-H. Sherry","family":"Chow","sequence":"additional","affiliation":[{"name":"From the College of Medicine, Arizona Cancer Center, University of Arizona; Arizona Clinical Research Center; AmpliMed Corp, Tucson; Premiere Oncology, Scottsdale, AZ; Scott & White Clinic, Temple, TX; and The Angeles Clinic and Research Institute, Santa Monica, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Betty","family":"Samulitis","sequence":"additional","affiliation":[{"name":"From the College of Medicine, Arizona Cancer Center, University of Arizona; Arizona Clinical Research Center; AmpliMed Corp, Tucson; Premiere Oncology, Scottsdale, AZ; Scott & White Clinic, Temple, TX; and The Angeles Clinic and Research Institute, Santa Monica, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"O'Day","sequence":"additional","affiliation":[{"name":"From the College of Medicine, Arizona Cancer Center, University of Arizona; Arizona Clinical Research Center; AmpliMed Corp, Tucson; Premiere Oncology, Scottsdale, AZ; Scott & White Clinic, Temple, TX; and The Angeles Clinic and Research Institute, Santa Monica, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn","family":"Grenier","sequence":"additional","affiliation":[{"name":"From the College of Medicine, Arizona Cancer Center, University of Arizona; Arizona Clinical Research Center; AmpliMed Corp, Tucson; Premiere Oncology, Scottsdale, AZ; Scott & White Clinic, Temple, TX; and The Angeles Clinic and Research Institute, Santa Monica, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evan","family":"Hersh","sequence":"additional","affiliation":[{"name":"From the College of Medicine, Arizona Cancer Center, University of Arizona; Arizona Clinical Research Center; AmpliMed Corp, Tucson; Premiere Oncology, Scottsdale, AZ; Scott & White Clinic, Temple, TX; and The Angeles Clinic and Research Institute, Santa Monica, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Dorr","sequence":"additional","affiliation":[{"name":"From the College of Medicine, Arizona Cancer Center, University of Arizona; Arizona Clinical Research Center; AmpliMed Corp, Tucson; Premiere Oncology, Scottsdale, AZ; Scott & White Clinic, Temple, TX; and The Angeles Clinic and Research Institute, Santa Monica, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"233","reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.1021\/jm030225v"},{"key":"R2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-2952(00)00380-4"},{"key":"R3","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V97.11.3544"},{"key":"R4","doi-asserted-by":"publisher","DOI":"10.1097\/00001813-200211000-00007"},{"key":"R5","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-1058-03"},{"key":"R6","doi-asserted-by":"publisher","DOI":"10.1080\/10428190500266210"},{"key":"R7","doi-asserted-by":"publisher","DOI":"10.1385\/IJGC:36:1:015"},{"key":"R8","unstructured":"Bicker U: BM 06 002: A new immunostimulating compound, in Chirigos MA (ed): Immune Modulation and Control of Neoplasia by Adjuvant Therapy . New York, NY, Raven Press, pp 389,1978-401"},{"key":"R9","unstructured":"Micksche M, Kokoschka EM, Sagaster P, et al: Phase I study for a new immunostimulating drug, BM 06 002, in man, in Chirigos MA (ed): Immune Modulation and Control of Neoplasia by Adjuvant Therapy . New York, NY, Raven Press, pp 403,1978-443"},{"key":"R10","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/86.3.228"},{"key":"R11","doi-asserted-by":"publisher","DOI":"10.1089\/aid.1992.8.633"},{"key":"R12","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/84.16.1238"},{"key":"R13","doi-asserted-by":"publisher","DOI":"10.1007\/BF00872858"},{"key":"R14","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/89.15.1138"},{"key":"R15","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/92.3.205"},{"key":"R16","doi-asserted-by":"publisher","DOI":"10.1016\/S0009-8981(98)00089-8"},{"key":"R17","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.20433"},{"key":"R18","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-03-0964"},{"key":"R19","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.24.22.9695-9704.2004"},{"key":"R20","doi-asserted-by":"publisher","DOI":"10.1016\/j.drup.2004.01.004"},{"key":"R21","doi-asserted-by":"publisher","DOI":"10.4161\/cbt.4.5.1704"},{"key":"R22","unstructured":"Scott J, Dorr RT, Samulitis B, et al: Imexon-based combination chemotherapy in A375 human melanoma and RPMI 8226 human myeloma cell lines. Cancer Chemother Pharmacol  PMID: 17333195 [epub ahead of print on February 28, 2007]"},{"key":"R23","doi-asserted-by":"publisher","DOI":"10.1097\/01.cad.0000236305.43209.f0"},{"key":"R24","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.2001.281.6.C1964"},{"key":"R25","doi-asserted-by":"publisher","DOI":"10.1007\/BF00710050"}],"container-title":["Journal of Clinical Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascopubs.org\/doi\/pdfdirect\/10.1200\/JCO.2006.08.9672","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,5,25]],"date-time":"2022-05-25T20:04:08Z","timestamp":1653509048000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascopubs.org\/doi\/10.1200\/JCO.2006.08.9672"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,5,1]]},"references-count":25,"journal-issue":{"issue":"13","published-print":{"date-parts":[[2007,5,1]]}},"alternative-id":["10.1200\/JCO.2006.08.9672"],"URL":"https:\/\/doi.org\/10.1200\/jco.2006.08.9672","relation":{},"ISSN":["0732-183X","1527-7755"],"issn-type":[{"value":"0732-183X","type":"print"},{"value":"1527-7755","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,5,1]]}}}