Pharmacokinetics of ifosfamide administered according to three different schedules in metastatic soft tissue and bone sarcomas.
Ifosfamide is a leading drug in soft tissue sarcoma therapy. Recently high dose therapy (>9 g/m2) has been introduced in different schemes to obtain a higher response rate. All these higher doses can be administered following two different schedules: continuous infusion 24 hours a day for 4-5 days or bolus administration for 5 consecutive days. In this study we compare the differences in the pharmacokinetic profile between the two schedules. In both schemes we saw a very important autoinduction phenomenon, with a corresponding half-life decrease and total body clearance increase during the days of therapy. The clearances were not directly correlated with the administered dose. We can conclude that ifosfamide continuous infusion therapy is equivalent to fractionated administration, at least from a pharmacokinetic point of view. Short-term infusion is subjectively better tolerated and is therefore preferred.
Comandone
A
A
Department of Clinical Oncology, San Giovanni Antica Sede Hospital, Turin, Italy.
Leone
L
L
Oliva
C
C
Frustaci
S
S
Monteleone
M
M
Colussi
A M
AM
Dal Canton
O
O
Bergnolo
P
P
Boglione
A
A
Bumma
C
C
D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000493:pharmacokinetics; D001711:Biotransformation; D001859:Bone Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D004317:Doxorubicin / Q000008:administration & dosage; D004334:Drug Administration Schedule; D004347:Drug Interactions; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D012509:Sarcoma / Q000188:drug therapy / Q000378:metabolism*; D012983:Soft Tissue Neoplasms / Q000188:drug therapy / Q000378:metabolism*
D018906:Antineoplastic Agents, Alkylating; D004317:Doxorubicin; D007069:Ifosfamide