Phase I-II study of escalating doses of amifostine combined with high-dose cyclophosphamide.
OBJECTIVE
To evaluate the feasibility and clinical effects of increasing doses of amifostine administered four times in 1 day with high-dose (HD) cyclophosphamide (CTX).


METHODS
A group of 16 patients with a diagnosis of lymphoma were treated with HD-CTX given at a total dose of 7 g/m2 subdivided into four doses, each preceded by increasing doses of amifostine. A group of 12 lymphoma patients previously treated with the same HD-CTX regimen was used as historical controls.


RESULTS
The dose of amifostine was escalated in cohorts of three patients each from 4x570 mg/m2 to 4x910 mg/m2 without severe toxic effects. Further patients were treated at the highest dose level. Side effects included a fall in blood pressure (always less than 20% of baseline value), asymptomatic hypocalcemia (from a median value of 2.4 to 1.7 mmol/l) and a decrease in creatinine clearance (from a median value of 102 to 85 ml/min). The parameters of hematotoxicity for patients treated in the study were not significantly different from those of the historical control patients.


CONCLUSIONS
Amifostine can be given safely at a dose of 910 mg/m2 four times in 1 day in combination with HD-CTX. With this schedule amifostine did not show a myeloprotective effect.
Ghielmini
M
M
Oncology Institute of Southern Switzerland, Ospedale San Giovanni, Bellinzona. mghielmini@ticino.com
Van der Bosch
S
S
Bosshard
M
M
Pampallona
S
S
Gabutti
L
L
Egger
H P
HP
Kiess
M
M
Cavalli
F
F
Sessa
C
C
D000293:Adolescent; D000328:Adult; D000368:Aged; D004999:Amifostine / Q000008:administration & dosage*; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects* / Q000627:therapeutic use; D001853:Bone Marrow / Q000187:drug effects*; D003520:Cyclophosphamide / Q000009:adverse effects* / Q000627:therapeutic use; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005240:Feasibility Studies; D006689:Hodgkin Disease / Q000188:drug therapy*; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy*; D008875:Middle Aged; D011355:Prodrugs / Q000008:administration & dosage*
D018906:Antineoplastic Agents, Alkylating; D011355:Prodrugs; D003520:Cyclophosphamide; D004999:Amifostine