Long-term results of the co-operative German-Austrian-Swiss osteosarcoma study group's protocol COSS-86 of intensive multidrug chemotherapy and surgery for osteosarcoma of the limbs.
BACKGROUND
In an effort to intensify osteosarcoma therapy, systemic ifosfamide was added pre- and postoperatively to an already aggressive three-drug regimen. In a subgroup of patients, loco-regional treatment intensification was attempted by using the intraarterial route to give cisplatin.


METHODS
Patients < or = 40 years at diagnosis of a localised, de novo high-grade central extremity osteosarcoma were eligible for inclusion into study COSS-86 if registered within three weeks from biopsy. Doxorubicin, high-dose methotrexate, and cisplatin were given to all patients. Patients who fulfilled one or more of three defined high-risk criteria received early systemic treatment intensification by adding ifosfamide as the fourth agent. Preoperatively, these high-risk patients received cisplatin either intraarterially or intravenously.


RESULTS
171 eligible patients were entered, of which 128 were stratified into the high-risk group. When all 171 were analysed by intention-to-treat, actuarial overall and event-free survival rates at ten years were 72% and 66%, respectively. No benefit of intraarterial cisplatin application was detected. Cumulative treatment toxicity was considerable.


CONCLUSIONS
In a multicenter setting, intensive treatment of osteosarcoma according to protocol COSS-86 led to long-term disease-free survival for two thirds of patients. We saw no benefit of using the intraarterial route to administer cisplatin.
Fuchs
N
N
Abteilung für Pädiatrische Hämatologie und Onkologie, Universitäts-Kinderklinik, Hamburg-Eppendorf, Germany.
Bielack
S S
SS
Epler
D
D
Bieling
P
P
Delling
G
G
Körholz
D
D
Graf
N
N
Heise
U
U
Jürgens
H
H
Kotz
R
R
Salzer-Kuntschik
M
M
Weinel
P
P
Werner
M
M
Winkler
K
K
D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001132:Arm / Q000473:pathology / Q000601:surgery; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D002675:Child, Preschool; D002945:Cisplatin / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage*; D007261:Infusions, Intra-Arterial; D007262:Infusions, Intravenous; D007866:Leg / Q000473:pathology / Q000601:surgery; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D020360:Neoadjuvant Therapy; D012516:Osteosarcoma / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D012307:Risk Factors; D016019:Survival Analysis; D016896:Treatment Outcome
D004317:Doxorubicin; D002945:Cisplatin; D007069:Ifosfamide; D008727:Methotrexate