{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T13:58:37Z","timestamp":1791899917452,"version":"4.3.4"},"reference-count":0,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCO"],"published-print":{"date-parts":[[1988,5]]},"abstract":"<jats:p> Forty-seven adult patients with glioblastoma multiforme (GBM) were treated in a phase I\/II study combining continuous intravenous (IV) infusions of iododeoxyuridine (IdUrd) and hyperfractionated radiation therapy. IdUrd was administered as a continuous infusion (24 h\/d) for two separate 14-day infusion periods. The dose of IdUrd was escalated from 500 to 1,200 mg\/m2\/d. The initial wide-field tumor volume was treated to 45 Gy at 1.5 Gy fractions twice daily over 3 weeks. Following a planned 2-week break, a reduced-field boost of 25 Gy was delivered using 1.25 Gy fractions twice daily over 2 weeks (total dose, 70 Gy over 9 weeks). The IdUrd infusion preceded both the wide-field and reduced-field irradiation by 1 week. All treatment was performed on an outpatient basis. Dose-limiting systemic toxicity to the bone marrow (primarily thrombocytopenia) and gastrointestinal (GI) tract (both stomatitis and diarrhea) established the maximum tolerable dose (MTD) at 1,000 mg\/m2\/d for a 14-day infusion. Significant local toxicity (within the radiation field) was not seen. The kinetics of IdUrd were linear with dose escalation and reached steady-state plasma concentrations of 1.3 to 3.4 mumol\/L. The total body clearance of IdUrd was .82 L\/min\/m2. The primary metabolite, 5-iodouracil (IUra) approached steady state by day 6 of the infusion when plasma levels were 60 times higher than IdUrd. Plasma levels of uracil and thymine, but not thymidine, were elevated throughout the infusion. With a minimum follow-up of 1 year, ten patients remain alive, while 33 patients died of progressive disease, and four patients died of other causes (including one treatment-related death). The median survival for all 47 patient and for the 40 patients receiving the MTD was 45 and 47 weeks, respectively, with 12% and 14% survivals at 24 months. Using a Cox regression analysis, age (less than or equal to 50 years v greater than 50 years) and pretreatment performance status (PS) (Eastern Cooperative Oncology Group [ECOG]-PS 0 to 1 v PS 2 to 3) were independent, statistically significant (P2 less than .05) predictors of survival, with the ECOG status being a better predictor. Patients with a PS 0 to 1 (28 patients) had a median survival of 64 weeks with 21% survival at 24 months, compared with a median survival of 29 weeks and 0% survival at 12 months in the 19 patients with PS 2 to 3. The overall and subgroup survival data are at least comparable to other combined modality treatment approaches in patients with GBM. <\/jats:p>","DOI":"10.1200\/jco.1988.6.5.871","type":"journal-article","created":{"date-parts":[[2017,2,23]],"date-time":"2017-02-23T18:23:30Z","timestamp":1487874210000},"page":"871-879","source":"Crossref","is-referenced-by-count":64,"title":["Pharmacology and phase I\/II study of continuous intravenous infusions of iododeoxyuridine and hyperfractionated radiotherapy in patients with glioblastoma multiforme."],"prefix":"10.1200","volume":"6","author":[{"given":"T J","family":"Kinsella","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Collins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Rowland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"R","family":"Klecker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D","family":"Wright","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D","family":"Katz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S M","family":"Steinberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E","family":"Glastein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"233","container-title":["Journal of Clinical Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascopubs.org\/doi\/pdfdirect\/10.1200\/JCO.1988.6.5.871","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,5,25]],"date-time":"2022-05-25T23:33:34Z","timestamp":1653521614000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascopubs.org\/doi\/10.1200\/JCO.1988.6.5.871"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1988,5]]},"references-count":0,"journal-issue":{"issue":"5","published-print":{"date-parts":[[1988,5]]}},"alternative-id":["10.1200\/JCO.1988.6.5.871"],"URL":"https:\/\/doi.org\/10.1200\/jco.1988.6.5.871","relation":{},"ISSN":["0732-183X","1527-7755"],"issn-type":[{"value":"0732-183X","type":"print"},{"value":"1527-7755","type":"electronic"}],"subject":[],"published":{"date-parts":[[1988,5]]}}}