title: Simultaneous infusion of high-dose cytosine arabinoside with cyclophosphamide followed by total body irradiation and marrow infusion for the treatment of patients with advanced hematological malignancy.
abstract: Nine patients with advanced hematological malignancy were entered into a phase I study to determine the maximum tolerated doses of cytosine arabinoside (Ara-C) and cyclophosphamide (CY) combined with a standard dose of total body irradiation (TBI). Ara-C was administered continuously over 36 h and two doses of CY were given at 24-h intervals during Ara-C administration. TBI was given as 2.0 Gy fractions on each of 6 consecutive days followed by bone marrow transplantation. The initial three patients received a total dose of 6048 mg/m2 of Ara-C and 84 mg/kg of CY, with two of three patients experiencing fatal toxicity. The next two patients received a total dose of 5040 mg/m2 of Ara-C and 70 mg/kg of CY and both experienced fatal toxicity. The next four patients received a total dose of 3024 mg/m2 of Ara-C, 56 mg/kg of CY; two patients had no toxicity but two had grade 4 (fatal) toxicity. Four of the six patients with fatal toxicity did not complete the TBI regimen and two of these did not receive marrow infusion. One patient is alive (greater than 547 days post-transplant) but has relapsed (day 305). It is concluded that phase I trials of regimens containing concurrent administration of Ara-C and CY may not be appropriate due to severe dose-independent toxicity as demonstrated in this study.
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, WA 98104.
authors.forename: F B
authors.initials: FB
authors.lastname: Petersen
authors.forename: F R
authors.initials: FR
authors.lastname: Appelbaum
authors.forename: C D
authors.initials: CD
authors.lastname: Buckner
authors.forename: J E
authors.initials: JE
authors.lastname: Sanders
authors.forename: R A
authors.initials: RA
authors.lastname: Clift
authors.forename: R
authors.initials: R
authors.lastname: McGuffin
authors.forename: S I
authors.initials: SI
authors.lastname: Bearman
authors.forename: N
authors.initials: N
authors.lastname: Flournoy
authors.forename: E D
authors.initials: ED
authors.lastname: Thomas
mesh_terms: D000293:Adolescent; D000328:Adult; D016026:Bone Marrow Transplantation; D002648:Child; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage* / Q000627:therapeutic use; D003561:Cytarabine / Q000008:administration & dosage* / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007938:Leukemia / Q000628:therapy*; D008297:Male; D014916:Whole-Body Irradiation
chemical_list: D003561:Cytarabine; D003520:Cyclophosphamide