Phase III trial of two investigational schedules of ifosfamide compared with standard-dose doxorubicin in advanced or metastatic soft tissue sarcoma: a European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group Study.
OBJECTIVE
Single-agent doxorubicin remains the standard treatment for advanced soft tissue sarcomas. Combining doxorubicin with standard-dose ifosfamide has not been shown to improve survival and is associated with a significantly increased toxicity; it is not known whether higher dose single-agent ifosfamide is superior to doxorubicin.


METHODS
This randomized prospective multicenter phase III trial was designed to compare progression-free survival of patients with advanced soft tissue sarcoma receiving either regimen of standard doxorubicin 75 mg/m2 every 21 days, ifosfamide 9 g/m2 over 3 days continuous infusion, or ifosfamide 3 g/m2 per day in 3 hours over 3 days. The primary end point was progression-free survival. Secondary end points included overall survival, response rate, and toxicity.


RESULTS
The study included 326 patients. Grade 4 leukopenia, neutropenia, febrile neutropenia, and encephalopathy were more frequent in the ifosfamide arms. Progression-free survival, overall survival, and response rates were not significantly different between the three arms. An independent data monitoring committee reviewed the interim data and recommended early closure of the trial for futility (ie, no significant difference would be shown).


CONCLUSIONS
Single-agent doxorubicin remains the treatment of choice for patients with advanced soft tissue sarcoma.
Lorigan
Paul
P
Weston Park Hospital, Sheffield, United Kingdom. Paul.Lorigan@christie-tr.nwest.nhs.uk
Verweij
Jaap
J
Papai
Zsuzsa
Z
Rodenhuis
Sjoerd
S
Le Cesne
Axel
A
Leahy
Michael G
MG
Radford
John A
JA
Van Glabbeke
Martine M
MM
Kirkpatrick
Anne
A
Hogendoorn
Pancras C W
PC
Blay
Jean-Yves
JY
D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage* / Q000009:adverse effects; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage* / Q000009:adverse effects; D007262:Infusions, Intravenous; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology; D009367:Neoplasm Staging; D011336:Probability; D011446:Prospective Studies; D018570:Risk Assessment; D012509:Sarcoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000556:secondary*; D016019:Survival Analysis; D016896:Treatment Outcome
D004317:Doxorubicin; D007069:Ifosfamide