title: An expanded phase I/II trial of cyclophosphamide, etoposide, and carboplatin plus total body irradiation with autologous marrow or stem cell support for patients with hematologic malignancies.
abstract: The major cause for failure of autologous stem cell transplantation for hematologic malignancies is the risk of recurrent disease. As a result, new treatment regimens that include novel agents or combinations of agents and approaches are needed. The current report describes a large Phase I/II, single-center trial that includes 60 patients with a variety of hematologic malignancies. These patients received a fixed dose of carboplatin (1 g/m(2)/d x 72 hours by CI) etoposide (600 mg/m(2)/d x 3 days) and cyclophosphamide (2 g/m(2)/d x 3 days), plus escalating doses of total body irradiation (TBI) (at 1000, 1200, and 1295 cGy) over 3 days. Eleven patients received infusion of autologous marrow, 32 received peripheral blood stem cells, and 17 patients received both. The maximum tolerated dose of this regimen was a radiation dose of 1200 cGy given in 200-cGy fractions BID x 3 days. The dose-limiting toxicity was mucositis, with 97% of patients requiring narcotic analgesia for mouth pain. Overall treatment-related mortality was 6.7%, with 2 of the 4 deaths occurring in a group of 9 patients aged 60 and older. Responses were seen in all patient groups, but the most encouraging outcomes were seen in 12 patients with high-risk or advanced acute myelocytic lymphoma (AML), 7 of whom remain alive and free of disease beyond 5 years. This regimen is intensive and causes considerable mucositis but is otherwise well tolerated and has demonstrated activity in a number of hematologic malignancies, especially AML.
authors.affiliation: Division of Medical Oncology, Campus Box #7305, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA. SheaT@med.unc.edu
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Shea
authors.forename: Rebecca
authors.initials: R
authors.lastname: Bruner
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Wiley
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Serody
authors.forename: Scott
authors.initials: S
authors.lastname: Sailer
authors.forename: Don A
authors.initials: DA
authors.lastname: Gabriel
authors.forename: Eileen
authors.initials: E
authors.lastname: Capel
authors.forename: Dominic T
authors.initials: DT
authors.lastname: Moore
authors.forename: Georgette
authors.initials: G
authors.lastname: Dent
authors.forename: Stuart
authors.initials: S
authors.lastname: Bentley
authors.forename: Mark E
authors.initials: ME
authors.lastname: Brecher
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016026:Bone Marrow Transplantation; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D019583:Dose Fractionation, Radiation; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D019337:Hematologic Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male; D008875:Middle Aged; D018714:Radiotherapy, Adjuvant; D013997:Time Factors; D014182:Transplantation, Autologous; D016896:Treatment Outcome; D014916:Whole-Body Irradiation
chemical_list: D005047:Etoposide; D003520:Cyclophosphamide; D016190:Carboplatin