Ifosfamide, carboplatin, and etoposide (ICE) in combination with regional hyperthermia (RHT) in chemotherapy-pretreated non.....

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Author(s): C. Nickenig, V. Buecklein, L. H. Lindner, S. Abdel-Rahman, M. Kuhlencordt, W. Hiddemann, R. D. Issels; University Hospital Medical Center Grosshadern, Munich, Germany; Argirov Klinik Starnberger See, Berg, Germany
Background: Regional hyperthermia (RHT) improves outcome in combination with neoadjuvant chemotherapy as first-line therapy in locally advanced HR-STS (Issels et al., Abstract 10009, ASCO 2007). Efficacy of ICE combined with RHT as second-line treatment strategy in pts with locally advanced HR-STS pretreated with anthracycline-based chemotherapy ± RHT was evaluated.

Methods: Between 9/97 and 6/08, 49 pts were treated with ICE + RHT (median age: 51 years, range: 21-74 years), with high-grade (G2 24 pts; G3 25 pts) STS histology (20 Lipo-Sa; 6 Leiomyo-Sa, 6 MPNST, 5 NOS, 2 DSRCT, 10 others). As first-line therapy 35 pts had received chemotherapy combined with RHT and 14 pts without RHT. Second-line ICE consisted of 1.5 g/m2 ifosfamide, 100 mg/m2 carboplatin, and 150 mg/m2 etoposide on days 1-4 combined with RHT on two days and was repeated on day 28 (4-6 cycles). Besides toxicity, primary and secondary endpoints were objective response (OR) (RECIST), progression free rate (PFR) at 3 and 6 months, and overall survival (OS).
Results: Pts received a median of 4 ICE cycles (range 1-8) in combination with RHT. Hematological toxicity grade III (11 pts)/ IV (23 pts) occurred in 34 pts (69 %), 3 pts (6 %) suffered from therapy-related deaths due to infection during cytopenia (2 pts) or postsurgery-related complications (1 pt). In 35 of 49 pts evaluable for OR, 26% achieved objective remission (1 CR + 8 PR), 51% showed stable disease (18 SD) and 23% progressive disease (8 PD). OR rates after initial chemotherapy with or without RHT were 17 % (4 PR of 24 pts) and 45% (1 CR + 4 PR of 11 pts), respectively (p=0.13). Irrespective of pretreatment, for all pts the PFR after 3 and 6 months was 87% (CI95=96%-77%) and 76% (CI95=88%-63%) and median OS was 22 months (CI95=29-16 months).
Conclusions: Second-line ICE combined with RHT is feasible and effective in pts with locally advanced HR-STS non-responding to first-line anthracycline-based chemotherapy with or without RHT. (Supported by Deutsche Krebshilfe and HelmholtzZentrum münchen - German Research Center for Environmental Health