A randomised phase II study on neo-adjuvant chemotherapy for 'high-risk' adult soft-tissue sarcoma

The aim of this study was to examine the strategy, feasibility and outcome of neo-adjuvant chemotherapy, with doxorubicin and ifosfamide, in adult pat ients with 'high-risk' soft-tissue sarcomas. patients with 'high-risk' soft -tissue sarcomas, defined as tumours greater than or equal to8 cm of any gr ade, or grade II/III tumours <8 cm, or grade II/III locally recurrent tumou rs, or grade II/III tumours with inadequate surgery performed in the previo us 6 weeks and therefore requiring further. surgery, were randomised betwee n either surgery alone or three cycles of 3-weekly doxorubicin 50 mg/m(2) i ntravenous (i.v.) bolus and ifosfamide 5 g/m(2) (24 h infusion) before surg ery. The type of surgery had to be planned at randomisation. Tumours were t o be amenable to surgery by amputation, compartmental resection, wide or ma rginal excision. If chemotherapy was given, surgery had to be peeformed wit hin 21 days after the last chemotherapy. Patients received postoperative ra diotherapy in cases of marginal surgery, microscopically incomplete resecti on and no further possibility for surgery, and in cases of surgery because of local recurrence. 150 patients were entered into the study and 134 were eligible, 67 in each arm. The most frequent side-effects of chemotherapy we re alopecia, nausea and vomiting (95%), and leucocytopenia (32%). One patie nt died of neutropenic fever after the first cycle of chemotherapy. Chemoth erapy did not interfere with planned surgery and did not affect postoperati ve wound healing. Limb-salvage was achieved in 88%, amputation was necessar y in 12% (all according to the plan at randomisation). The trial was closed after completion of phase II, since accrual was too slow to justify expand ing the study into the scheduled phase III study. At a median follow-up of 7.3 years, the 5 year disease-free survival is estimated at 52% for the no chemotherapy and 56% for the chemotherapy arm (standard error: 7%) (P = 0.3 548). The 5 year overall survival for both arms is 64 and 65%, respectively (standard error 7%) (P = 0.2204). Neo-adjuvant-chemotherapy with doxorubic in and ifosfamide at these doses and with this schedule was feasible and di d not compromise subsequent treatment, surgery with or without radiotherapy . Although not powered to draw definitive conclusions on benefit, but with an at least 7 year median follow-up, the results render it less likely that major survival benefits will be achieved with this type: of chemotherapy. (C) 2001 Elsevier Science Ltd. All rights reserved.