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.
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.
Shea
Thomas C
TC
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
Bruner
Rebecca
R
Wiley
Joseph M
JM
Serody
Jonathan S
JS
Sailer
Scott
S
Gabriel
Don A
DA
Capel
Eileen
E
Moore
Dominic T
DT
Dent
Georgette
G
Bentley
Stuart
S
Brecher
Mark E
ME
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
D005047:Etoposide; D003520:Cyclophosphamide; D016190:Carboplatin