Purpose. The present prospective randomized adjuvant trial was
carried out to compare the toxicity, feasibility and efficacy of augmented chemotherapy
added to hyperfractionated accelerated radiotherapy after wide or marginal resection of grade
2 and grade 3 soft tissue sarcoma (STS).Patients and methods. Fifty-nine patients underwent primary surgery
by wide or marginal excision and were subsequently randomized to receive radiotherapy
alone or under the addition of six courses of ifosfamide (1500 mg/m2
, days 1–4), dacarbazine
(DTIC) (200 mg/m2
, days 1–4) and doxorubicin (25 mg/m2
, days 1–2) administered in
14-day-intervals supported by granulocyte-colony stimulating factor (30 × 106
IU/day, s.c.)
on days 5–13. According to the randomization protocol, 28 patients received radiotherapy
only, whereas 31 patients were treated with additional chemotherapy.Results. The relative ifosfamide–doxorubicin–DTIC (IFADIC) dose
intensity achieved was 93%. After a mean observation period of 41±19.7 months
(range, 8.1–84 months), 16 patients (57%) in the control group versus 24 patients (77%) in the
chemotherapy group were free of disease (p>0.05).Within the control group, tumor relapses
occurred in 12 patients (43%;six patients with distant metastases, two with local relapse,
four with both) versus seven patients (23%; five patients with distant metastases, one with
local recurrence, one with both) from the chemotherapy group. Relapse-free survival (RFS)
(p=0.1), time to local failure (TLF) (p=0.09), time to distant failure (TDF) (p=0.17) as well as
overall survival (OS) (p=0.4) did not differ significantly between the two treatment groups.
Treatment-related toxicity was generally mild in both treatment arms.Conclusion. We conclude that the safety profile of intensified IFADIC
added to radiotherapy was manageable and tolerable in the current setting. Inclusion
of intensified IFADIC was not translated into a significant benefit concerning OS, RFS,
TLF andTDF as compared with radiotherapy only, although a potential benefit of
chemotherapy for grade 3 STS patients needs to be validated in prospective randomized
trials including larger patient numbers.
