TY - JOUR
T1 - Adjuvant chemotherapy with doxorubicin, ifosfamide, and lenograstim for resected soft-tissue sarcoma (EORTC 62931)
T2 - A multicentre randomised controlled trial
AU - Woll, Penella J.
AU - Reichardt, Peter
AU - Le Cesne, Axel
AU - Bonvalot, Sylvie
AU - Azzarelli, Alberto
AU - Hoekstra, Harald J.
AU - Leahy, Michael
AU - Van Coevorden, Frits
AU - Verweij, Jaap
AU - Hogendoorn, Pancras C.W.
AU - Ouali, Monia
AU - Marreaud, Sandrine
AU - Bramwell, Vivien H.C.
AU - Hohenberger, Peter
N1 - Funding Information:
This publication was supported by the National Cancer Institute (Bethesda, MD, USA; numbers 2U10 CA11488-25 through 5U10 CA011488-33 ), Cancer Research UK, the European Organisation for Research and Treatment of Cancer (EORTC) Charitable Trust. NCIC CTG participation in this study was supported by the Canadian Cancer Society Research Institute ( grant numbers 015469 and 021039 ). An unrestricted grant was given by Rhone-Poulenc-Rorer to support the study, with local support from them and Chugai Pharma for lenograstim supplies. This report is solely the responsibility of the authors and does not necessarily reflect the official views of the funders. We thank the patients who volunteered for this study and the clinicians who cared for them; Derek Crowther, Martine van Glabbeke, and Martin Robinson for contributing to the design of the trial; Anne Kirkpatrick and Catherine Hermans for data management.
PY - 2012/10/1
Y1 - 2012/10/1
N2 - Background: The effect of adjuvant chemotherapy on survival for resected soft-tissue sarcoma remains unknown. We investigated the effect of intensive adjuvant chemotherapy on survival in patients after resection of high-risk soft-tissue sarcomas. Methods: In this multicentre randomised trial, patients with macroscopically resected, Trojani grade II-III soft-tissue sarcomas at any site, no metastases, performance status lower than 2 and aged between 16 and 70 years were eligible within 4 weeks of definitive surgery. Patients were randomly assigned to receive adjuvant chemotherapy or no chemotherapy (control group). Randomisation was done with a minimisation technique, stratified by hospital, site of primary tumour, tumour size, planned radiotherapy, and isolated limb perfusion therapy. Chemotherapy consisted of five cycles of doxorubicin 75 mg/m2, ifosfamide 5 g/m2, and lenograstim every 3 weeks. Patients in both groups received radiotherapy if the resection was marginal or the tumour recurrent. The primary endpoint was overall survival and analyses were done by intention to treat. The final results are presented. This trial is registered with ClinicalTrials.gov, NCT00002641. Findings: Between February, 1995, and December, 2003, 351 patients were randomly assigned to the adjuvant chemotherapy group (175 patients) or to the control group (176). 258 (73%) of 351 patients received radiotherapy, 129 in each group. Overall survival did not differ significantly between groups (hazard ratio [HR] 0·94 [95% CI 0·68-1·31], p=0·72) nor did relapse-free survival (HR 0·91 [0·67-1·22], p=0·51). 5-year overall survival rate was 66·5% (58·8-73·0) in the chemotherapy group and 67·8% (60·3-74·2) in the control group. Chemotherapy was well tolerated, with 130 (80%) of 163 patients who started it completing all five cycles. 16 (10%) patients had grade 3 or 4 fever or infection, but no deaths due to toxic effects were recorded. Interpretation: Adjuvant chemotherapy with doxorubicin and ifosfamide in resected soft-tissue sarcoma showed no benefit in relapse-free survival or overall survival. Future studies should focus on patients with larger, grade III, and extremity sarcomas. Funding: European Organisation for Research and Treatment of Cancer, Rhone-Poulenc-Rorer.
AB - Background: The effect of adjuvant chemotherapy on survival for resected soft-tissue sarcoma remains unknown. We investigated the effect of intensive adjuvant chemotherapy on survival in patients after resection of high-risk soft-tissue sarcomas. Methods: In this multicentre randomised trial, patients with macroscopically resected, Trojani grade II-III soft-tissue sarcomas at any site, no metastases, performance status lower than 2 and aged between 16 and 70 years were eligible within 4 weeks of definitive surgery. Patients were randomly assigned to receive adjuvant chemotherapy or no chemotherapy (control group). Randomisation was done with a minimisation technique, stratified by hospital, site of primary tumour, tumour size, planned radiotherapy, and isolated limb perfusion therapy. Chemotherapy consisted of five cycles of doxorubicin 75 mg/m2, ifosfamide 5 g/m2, and lenograstim every 3 weeks. Patients in both groups received radiotherapy if the resection was marginal or the tumour recurrent. The primary endpoint was overall survival and analyses were done by intention to treat. The final results are presented. This trial is registered with ClinicalTrials.gov, NCT00002641. Findings: Between February, 1995, and December, 2003, 351 patients were randomly assigned to the adjuvant chemotherapy group (175 patients) or to the control group (176). 258 (73%) of 351 patients received radiotherapy, 129 in each group. Overall survival did not differ significantly between groups (hazard ratio [HR] 0·94 [95% CI 0·68-1·31], p=0·72) nor did relapse-free survival (HR 0·91 [0·67-1·22], p=0·51). 5-year overall survival rate was 66·5% (58·8-73·0) in the chemotherapy group and 67·8% (60·3-74·2) in the control group. Chemotherapy was well tolerated, with 130 (80%) of 163 patients who started it completing all five cycles. 16 (10%) patients had grade 3 or 4 fever or infection, but no deaths due to toxic effects were recorded. Interpretation: Adjuvant chemotherapy with doxorubicin and ifosfamide in resected soft-tissue sarcoma showed no benefit in relapse-free survival or overall survival. Future studies should focus on patients with larger, grade III, and extremity sarcomas. Funding: European Organisation for Research and Treatment of Cancer, Rhone-Poulenc-Rorer.
UR - http://www.scopus.com/inward/record.url?scp=84866901248&partnerID=8YFLogxK
U2 - 10.1016/S1470-2045(12)70346-7
DO - 10.1016/S1470-2045(12)70346-7
M3 - Article
C2 - 22954508
AN - SCOPUS:84866901248
SN - 1470-2045
VL - 13
SP - 1045
EP - 1054
JO - The Lancet Oncology
JF - The Lancet Oncology
IS - 10
ER -