title: Biweekly administration of 24-h infusion of irinotecan followed by a 1-h infusion of docetaxel: a phase I study.
abstract: We developed a chemotherapy combination regimen based on preclinical data suggesting synchronization of cancer cells in G2/M phase when exposed to irinotecan over a protracted period. This phase I study aimed to determine the toxicity spectrum, and define the dose-limiting toxicity (DLT), maximum tolerated dose (MTD) and recommended optimal dose (ROD) of irinotecan infused over 24 h and followed by a 1-h infusion of 30 mg/m2 docetaxel. Starting dose for irinotecan was 30 mg/m2 and escalation proceeded at 30 mg/m2 increments, in cohorts of three to six patients until the MTD was reached. A dose between the MTD and the previous level was explored to further define the ROD. Thirty-two patients with advanced refractory cancers (median age 64, 19 male) received 190 treatment courses at five dosing levels of irinotecan: 30 mg/m2 (n=6 patients), 60 (n=3), 90 (n=7), 120 (n=8) and 105 (n=8). The MTD and ROD was 120/30 and 105/30 mg/m2. DLTs were diarrhea and neutropenia. Antitumor activity was modest. The ROD of biweekly administration of 24-h irinotecan followed by 1-h docetaxel is 105 and 30 mg/m2, respectively. The low hematological toxicity and modest activity observed leave questions concerning the optimal timing of this combination.
authors.affiliation: Department of Medical Oncology, Ioannina University Hospital, Ioannina, Greece. ebriasou@otenet.gr
authors.forename: E
authors.initials: E
authors.lastname: Briasoulis
authors.forename: G
authors.initials: G
authors.lastname: Pentheroudakis
authors.forename: H
authors.initials: H
authors.lastname: Timotheadou
authors.forename: D
authors.initials: D
authors.lastname: Rammou
authors.forename: N
authors.initials: N
authors.lastname: Pavlidis
authors.forename: G
authors.initials: G
authors.lastname: Fountzilas
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D017322:Clinical Trials, Phase II as Topic; D003967:Diarrhea / Q000139:chemically induced; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006115:Greece; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D007262:Infusions, Intravenous / Q000379:methods*; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D018579:Patient Selection; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D028761:Withholding Treatment / Q000941:ethics
chemical_list: D043823:Taxoids; D000077143:Docetaxel; D000077146:Irinotecan; D002166:Camptothecin