Efficacy of consolidation high-dose chemotherapy with ifosfamide, carboplatin and etoposide (HD-ICE) followed by autologous peripheral blood stem cell rescue in chemosensitive patients with metastatic soft tissue sarcomas

Background: Prognosis of patients with metastatic soft tissue
sarcomas (MSTS) is poor even after response to doxorubicin-based
chemotherapy. We report phase II data of highdose chemotherapy and
peripheral blood stem cell (PBSC) rescue in patients with MSTS
responding to AI-G chemotherapy. Patients and Methods: From 1997 to
2002, 55 patients with MSTS were prospectively treated with 4
cycles of AI-G (doxorubicin 75 mg/m(2), ifosfamide 6 g/m(2) with
G-CSF support). Responders received 2 further cycles of AI-G with
collection of PBSCs. High-dose chemotherapy consisted of ifosfamide
12 g/m(2), carboplatin 1.2 g/m(2) and etoposide 1.2 g/m(2) (HD-ICE)
followed by reinfusion of PBSCs. Results: Twenty-one of 55 patients
(38%) were assessed as responders (3 complete response, 18 partial
response). All but 2 patients refusing treatment received high-dose
chemotherapy with PBSC rescue leading to grade IV hematologic
toxicity without severe infections in all patients. No toxic death
occurred. After a median follow-up time of 30 months, the median
progression-free time was 12 months and survival time was 22 months
for the entire group. By intent-totreat analysis the probability of
5-year progression-free survival was significantly higher for
patients allocated to HD-ICE compared to patients receiving
second-line chemotherapy after failure of AI-G (14 vs. 3%; p =
0.003). The estimated 5-year overall survival between the 2 groups
was different (27% vs. not reached) but did not reach significance
(p = 0.08). Conclusion: HD-ICE is feasible and promising in
patients with chemosensitive MSTS. A randomized phase III trial is
warranted to further define the role of HD-ICE as consolidation
treatment in these patients.