Effect of high-dose ifosfamide in advanced soft tissue sarcomas. A multicentre phase II study of the EORTC Soft Tissue and Bone Sarcoma Group.
In this phase II study the effect of high-dose ifosfamide (HDI) given as a 3-day continuous infusion at a dose of 12 g/m2 repeated every 4 weeks with adequate mesna protection and hydration was evaluated in patients with advanced soft tissue sarcomas. A total of 124 patients entered the trial of which 10 were ineligible. HDI was given both as first-line and second-line chemotherapy. Median age was 46 years (19-66 years). Median World Health Organization (WHO) performance status was 1 (0-1). Fifty two per cent of the patients were males. The predominant histology was leiomyosarcoma (33%). A maximum of six cycles was given. At the time of analysis 55 patients have died. The partial response (PR) rate was 16%. The median time to progression was 15 weeks. 8 of the 18 responding patients (44%) had synovial sarcomas, whereas only 5% of the patients having leiomyosarcomas responded. The grade 3 + 4 haematological toxicity encountered was neutrophils in 78% and platelets in 12%. The major grade 3 + 4 non-haematological toxicities encountered were febrile neutropenia in 39%, infection in 20%, and acute renal failure in 4%. In conclusion, it is possible to administer HDI on a multicentre basis, but the toxicity is substantial. HDI given as a continuous infusion at this dose cannot be recommended as the standard treatment of advanced soft tissue sarcomas, even in selected patients.
Nielsen
O S
OS
Centre for Bone and Soft Tissue Sarcomas, Aarhus University Hospital, Denmark. osn@onko.aau.dk
Judson
I
I
van Hoesel
Q
Q
le Cesne
A
A
Keizer
H J
HJ
Blay
J Y
JY
van Oosterom
A
A
Radford
J A
JA
Svancárová
L
L
Krzemienlecki
K
K
Hermans
C
C
van Glabbeke
M
M
Oosterhuis
J W
JW
Verweij
J
J
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D010349:Patient Compliance; D012509:Sarcoma / Q000188:drug therapy* / Q000401:mortality; D016019:Survival Analysis
D018906:Antineoplastic Agents, Alkylating; D007069:Ifosfamide