Preoperative chemo-radiation therapy for localised retroperitoneal sarcoma: a phase I-II study from the Italian Sarcoma Group.

Abstract

BACKGROUND:

To study feasibility, safety and activity of the combination of high-dose long-infusion ifosfamide (HLI) and radiotherapy (RT) as preoperative treatment for resectable localised retroperitoneal sarcoma (RPS).

METHODS:

Patients received three cycles of HLI (14 g/m2). RT was started in combination with second cycle and administered up to a total dose of 50.4 Gy. Surgery was scheduled 4-6 weeks after the end of RT. Primary end-point was 3-year relapse free survival (RFS). The trial is registered with ITASARC_∗II_2004_003.

FINDINGS:

Between December 2003 and 2010, 83 patients were recruited. Main histological subtypes were well differentiated liposarcoma (19/83, 23%), dedifferentiated liposarcoma (26/83, 31%), leiomyosarcoma (14/83, 17%). Median tumour size was 120 mm (interquartile (IQ) range=82-160). The overall preoperative treatment was completed in 60 patients. Chemotherapy (CT) was completed in 65, while RT in 73. Four patients progressed before surgery and were not operated. 79 patients underwent surgery. At a median follow-up of 4.8 years (IQ range = 3-6.1), 23 and 15 patients developed local recurrence (LR) and distant metastases (DM); 30 patients died of disease. 3 and 5-year RFS and overall survival were 0.56 (90% confidence interval (CI): 0.45, 0.65) and 0.44 (90% CI: 0.27, 0.48), and 0.74 (90% CI: 0.62, 0.81) and 0.59 (90% CI: 0.33, 0.58). Crude cumulative incidence of LR and DM at 5 years were 0.37 (standard error (SE): 0.06) and 0.26 (SE: 0.06).

INTERPRETATION:

The combination of preoperative HLI and RT was feasible in two thirds of patients, while preoperative RT could be completed in most (73/83). Although a systemic coverage can be added to RT when this is felt to be appropriate, the ongoing international phase III trial is exploring the role of RT alone.

FUNDING:

This is a pure academic trial. No funding sources contributed to it.

• Authors: Alessandro Gronchi, Antonino De Paoli, Carla Dani, Domenico Franco Merlo, Vittorio Quagliuolo, Giovanni Grignani, Giulio Bertola, Piera Navarria, Claudia Sangalli, Angela Buonadonna, Rita De Sanctis, Roberta Sanfilippo, Angelo Paolo Dei Tos, Silvia Stacchiotti, Laura Giorello, Marco Fiore, Paolo Bruzzi, Paolo Giovanni Casali
• Journal: European journal of cancer (Oxford, England : 1990) (Eur J Cancer) Vol. 50 Issue 4 Pg. 784-92 (Mar 2014) ISSN: 1879-0852 [Electronic] England
• PMID: 24316063 (Publication Type: Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article, Multicenter Study)
• Copyright: Copyright © 2013 Elsevier Ltd. All rights reserved.

Chemical References

• Ifosfamide

Topics

• Aged
• Chemoradiotherapy, Adjuvant (adverse effects, methods)
• Combined Modality Therapy
• Feasibility Studies
• Humans
• Ifosfamide (administration & dosage, adverse effects)
• Italy
• Middle Aged
• Preoperative Care (adverse effects, methods)
• Radiotherapy Dosage
• Retroperitoneal Neoplasms (mortality, pathology, therapy)
• Sarcoma (mortality, pathology, therapy)
• Survival Analysis