title: Short, full-dose adjuvant chemotherapy (CT) in high-risk adult soft tissue sarcomas (STS): long-term follow-up of a randomized clinical trial from the Italian Sarcoma Group and the Spanish Sarcoma Group.
abstract: To report on long-term results of a phase 3 trial comparing three versus five cycles of adjuvant chemotherapy (CT) with full-dose epirubicin+ifosfamide in high-risk soft tissue sarcomas (STS).
  
  
  
  Patients (pts) were randomized to receive three preoperative cycles of epirubicin 120 mg/m2and ifosfamide 9 g/m2(Arm A) or to receive the same three preoperative cycles plus two postoperative cycles (Arm B). Radiotherapy could be either delivered in the preoperative or in the postoperative setting. Non-inferiority of the primary end point, OS, was assessed by the confidence interval of the hazard ratio (HR; Arm A/Arm B) derived from Cox model.
  
  
  
  Between January 2002 and April 2007, 164 pts were assigned to arm A and 164 to arm B. At a median follow-up (FU) of 117 months (IQ range 103-135 months), 123 deaths were recorded: 58 in Arm A and 65 in Arm B. Ten-year OS was 61% for the entire group of patients: 64% in Arm A and 59% in Arm B. The intention-to-treat analysis confirmed that three cycles were not inferior to five cycles (one-sided 95% upper confidence limit was 1.24). A per protocol analysis was consistent with these results. Pts with leiomyosarcoma and undifferentiated pleomorphic sarcoma (UPS) had the lowest, and the highest response rates, respectively. Consistently, Leiomyosarcoma and UPS had the worse and the best prognosis, respectively.
  
  
  
  At a longer FU, the non-inferiority of three cycles of a full-dose conventional CT in comparison to five is confirmed. Response to therapy is also confirmed to be associated with better survival. This regimen is currently tested within an ongoing international trial against three cycles of a neoadjuvant histology-tailored CT (ClinicalTrials.gov Identifier: NCT01710176).
authors.affiliation: Department of Surgery alessandro.gronchi@istitutotumori.mi.it.
authors.forename: A
authors.initials: A
authors.lastname: Gronchi
authors.affiliation: Department of Cancer Medicine.
authors.forename: S
authors.initials: S
authors.lastname: Stacchiotti
authors.affiliation: Department of Unit of Medical Statistics, Biometry and Bioinformatics, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan.
authors.forename: P
authors.initials: P
authors.lastname: Verderio
authors.affiliation: Department of Cancer Medicine, Istituto Ortopedico Rizzoli, Bologna, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Ferrari
authors.affiliation: Department of Cancer Medicine, Hospital Universitario Virgen del Rocio, Sevilla.
authors.forename: J
authors.initials: J
authors.lastname: Martin Broto
authors.affiliation: Department of Cancer Medicine, Hospital de la Santa Creu i Sant Pau, Barcelona.
authors.forename: A
authors.initials: A
authors.lastname: Lopez-Pousa
authors.affiliation: Department of Pathology, Medical School University of Valencia, Valencia, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Llombart-Bosch
authors.affiliation: Department of Pathology, Treviso General Hospital, Treviso.
authors.forename: A P
authors.initials: AP
authors.lastname: Dei Tos
authors.affiliation: Department of Pathology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Collini
authors.affiliation: Department of Cancer Medicine, University of Canarias Hospital, La Laguna, Spain.
authors.forename: J Cruz
authors.initials: JC
authors.lastname: Jurado
authors.affiliation: Department of Radiation Oncology, Centro di Riferimento Oncologico, Aviano.
authors.forename: A
authors.initials: A
authors.lastname: De Paoli
authors.affiliation: Department of Orthopedic Oncology, Istituto Ortopedico Rizzoli, Bologna, Italy.
authors.forename: D M
authors.initials: DM
authors.lastname: Donati
authors.affiliation: Department of Cancer Medicine, Valencian Oncologic Institute, Valencia, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Poveda
authors.affiliation: Department of Surgery, Humanitas Cancer Center, Rozzano.
authors.forename: V
authors.initials: V
authors.lastname: Quagliuolo
authors.affiliation: Department of Cancer Medicine, Presidio Sanitario Gradenigo, Torino.
authors.forename: A
authors.initials: A
authors.lastname: Comandone
authors.affiliation: Department of Cancer Medicine, IRCC Fondazione Piemontese per la Ricerca sul Cancro, Candiolo.
authors.forename: G
authors.initials: G
authors.lastname: Grignani
authors.affiliation: Department of Radiology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan.
authors.forename: C
authors.initials: C
authors.lastname: Morosi
authors.affiliation: Department of Radiology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan.
authors.forename: A
authors.initials: A
authors.lastname: Messina
authors.affiliation: Department of Cancer Medicine, Humanitas Cancer Center, Rozzano.
authors.forename: R
authors.initials: R
authors.lastname: De Sanctis
authors.affiliation: Department of Unit of Medical Statistics, Biometry and Bioinformatics, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan.
authors.forename: S
authors.initials: S
authors.lastname: Bottelli
authors.affiliation: Department of Cancer Medicine.
authors.forename: E
authors.initials: E
authors.lastname: Palassini
authors.affiliation: Department of Cancer Medicine.
authors.forename: P G
authors.initials: PG
authors.lastname: Casali
authors.affiliation: Laboratory of Oncologic Research, Istituto Ortopedico Rizzoli, Bologna, Italy.
authors.forename: Piero
authors.initials: P
authors.lastname: Picci
mesh_terms: D000328:Adult; D000368:Aged; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007890:Leiomyosarcoma / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012307:Risk Factors; D012509:Sarcoma / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy; D016896:Treatment Outcome
keywords: adjuvant chemotherapy; quality of surgery; response; sarcoma; soft tissue sarcoma; survival