Dose escalation of busulfan with pentoxifylline and ciprofloxacin in patients with breast cancer undergoing autologous transplants.
OBJECTIVE
There is evidence that pentoxifylline (PTX) and ciprofloxacin (Cipro) may protect patients from the effects of chemotherapy and radiation, which could allow further drug dose escalation. This study was conducted to determine whether oral and intravenous (IV) PTX and Cipro permits increased dose levels of oral busulfan (BU) with a fixed dose of IV cyclophosphamide (CY) in patients with breast cancer receiving autologous or syngeneic hematopoetic cell transplantation.


METHODS
Sixty-seven patients received PTX and Cipro with CY of 150 mg/kg and escalating doses of BU. The BU dosing began at 15 mg/kg, escalating in 1 mg/kg increments in groups of 4 patients. If no grade 3 or 4 regimen- related toxicities (RRT) were observed, the next 4 patients were treated at a higher dose.


RESULTS
Excessive RRT was not observed until BU 21 mg/kg was reached. Two patients at this dose level had RRTs and their BU steady-state concentration (Css) were 1,414 and 1,545 ng/ml. At a BU dose of 20 mg/kg , average BU Css 1,280 ng/ml, 0/4 had RRT. Among 10 patients who had BU Css targeted to 1,350 ng/ml, RRTs occurred in 2 (20%).


CONCLUSIONS
In this preliminary study with PTX and Cipro, the maximum tolerated dose of BU that can be given with CY (150 mg/kg) was 20 mg/kg, a BU Css of approximately 1,300 ng/ml. A randomized trial is necessary to determine whether PTX and Cipro reduce the toxicities of this regimen.
Bensinger
William I
WI
Fred Hutchinson Cancer Research Center, and University of Washington School of Medicine Seattle, Wash., USA. wbensing@fhcrc.org
Buckner
C Dean
CD
Lilleby
Kathy
K
Holmberg
Leona
L
Storb
Rainer
R
Slattery
John T
JT
D000328:Adult; D000890:Anti-Infective Agents / Q000008:administration & dosage*; D016026:Bone Marrow Transplantation; D001943:Breast Neoplasms / Q000601:surgery*; D002066:Busulfan / Q000008:administration & dosage* / Q000009:adverse effects; D002939:Ciprofloxacin / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D010431:Pentoxifylline / Q000008:administration & dosage*; D014182:Transplantation, Autologous; D014185:Transplantation, Isogeneic
D000890:Anti-Infective Agents; D007166:Immunosuppressive Agents; D002939:Ciprofloxacin; D002066:Busulfan; D010431:Pentoxifylline