Short, full-dose adjuvant chemotherapy in high-risk adult soft tissue sarcomas: a randomized clinical trial from the Italian Sarcoma Group and the Spanish Sarcoma Group.
OBJECTIVE
A previous randomized clinical trial by the Italian Sarcoma Group (ISG) had shown a survival benefit of adjuvant chemotherapy (CT) in high-risk extremity soft tissue sarcoma (STS). However, the dose-intensity of the last two cycles was suboptimal. We then undertook a multicentric international phase III study to compare three and five cycles of the same CT.


METHODS
Patients were randomly assigned either to receive three cycles of preoperative CT with epirubicin 120 mg/m(2) and ifosfamide 9 g/m(2) and granulocyte colony-stimulating factor (arm A) or to receive the same three cycles of preoperative CT followed by two further cycles of postoperative CT (arm B). Noninferiority of the primary end point, overall survival (OS), was assessed by the CI of the hazard ratio (HR; arm A/arm B) obtained from the Cox model.


RESULTS
Between January 2002 and April 2007, 328 patients were recruited (164 patients in each arm). At a median follow-up of 63 months (interquartile range, 49 to 77 months), 100 deaths were recorded, 49 in arm A and 51 in arm B. Five-year OS probability was 0.70 for the entire group of patients (0.68 in arm A and 0.71 in arm B). The HR of arm A versus arm B was 1.00 (90% CI, 0.72 to 1.39).


CONCLUSIONS
In this population of patients with high-risk localized STS, three cycles of full-dose preoperative CT were not inferior to five cycles. The outcome compares favorably with the expected survival of patients with high-risk STS and was superimposable on the CT arm of the previous ISG trial.
Fondazione Istituto di Ricovero e Cura a Carattere Scientifico, Istituto Nazionale Tumori, Milano, Italy. alessandro.gronchi@istitutotumori.mi.it
Alessandro
A
Gronchi
Sergio
S
Frustaci
Mario
M
Mercuri
Javier
J
Martin
Antonio
A
Lopez-Pousa
Paolo
P
Verderio
Lidia
L
Mariani
Pinuccia
P
Valagussa
Rosalba
R
Miceli
Silvia
S
Stacchiotti
Angelo Paolo
AP
Dei Tos
Antonino
A
De Paoli
Alessandra
A
Longhi
Andres
A
Poveda
Vittorio
V
Quagliuolo
Alessandro
A
Comandone
Paolo Giovanni
PG
Casali
Piero
P
Picci
D000293:Adolescent; D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D017024:Chemotherapy, Adjuvant; D004334:Drug Administration Schedule; D015251:Epirubicin / Q000008:administration & dosage; D005500:Follow-Up Studies; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D007558:Italy; D008875:Middle Aged; D012509:Sarcoma / Q000188:drug therapy* / Q000401:mortality; D012983:Soft Tissue Neoplasms / Q000188:drug therapy* / Q000401:mortality; D013030:Spain
D000903:Antibiotics, Antineoplastic; D018906:Antineoplastic Agents, Alkylating; D016179:Granulocyte Colony-Stimulating Factor; D015251:Epirubicin; D007069:Ifosfamide