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

• DOI: 10.1200/jco.2011.37.7218
• Publication Date: 2012-02-07T08:29:54Z
• Authors: Alessandro Gronchi; Sergio Frustaci; Mario Mercuri; Javier Martin; Antonio Lopez-Pousa; Paolo Verderio; Lidia Mariani; Pinuccia Valagussa; Rosalba Miceli; Silvia Stacchiotti; Angelo Paolo Dei Tos; Antonino De Paoli; Alessandra Longhi; Andres Poveda; Vittorio Quagliuolo; Alessandro Comandone; Paolo Giovanni Ca...; Piero Picci
• Keywords: Adult; Antibiotics, Antineoplastic; Adolescent; Sarcoma; Soft Tissue Neoplasms; Middle Aged; Drug Administration Schedule; 3. Good health; 03 medical and health sciences; 0302 clinical medicine; Italy; Oncology; Cancer Research; Chemotherapy, Adjuvant; Spain; Antineoplastic Combined Chemotherapy Protocols; Granulocyte Colony-Stimulating Factor; Humans; Ifosfamide; Antineoplastic Agents, Alkylating; Aged; Epirubicin; Follow-Up Studies

PurposeA 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.Patients and MethodsPatients were randomly assigned either to receive three cycles of preoperative CT with epirubicin 120 mg/m2and ifosfamide 9 g/m2and 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.ResultsBetween 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).ConclusionIn 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.