Abstract
ABSTRACT Background In patients with unresectable CRC LM there is an increasing tendency to combine systemic chemotherapy (CT) with local tumour destruction by RFA. Many retrospective studies indicate a possible benefit of this approach but definite proof was only obtained recently. Methods In a randomised phase II intergroup study conducted by the EORTC the benefits of adding RFA to systemic CT was evaluated in patients with ≤9 unresectable CRC LM and no extrahepatic disease. Between 2002 and 2007, 119 pts were randomised between CT alone (59) or RFA plus CT (60) In both arms, CT consisted of 6 months FOLFOX (oxaliplatin 85mg/m2 and LV5FU2) plus, since October 2005, bevacizumab. The primary objective was to exclude a 30-months overall survival (OS) rate ≤38% with RFA + CT (Fleming Design). Safety and progression free survival (PFS) were secondary endpoints. Results Baseline characteristics were similar between arms: 60% had ≥ 4 LM. 51 patients (85%) received CT in the RFA + CT arm and 59 (all) in the CT arm. The median number of CT cycles for patients who started CT was 10 in both arms. Toxicity profiles for CT were comparable between both arms. At a median follow up of 4.4 years, the 30-month OS rate was 61.7% (95% CI, 48.21-73.93) in the RFA +CT arm and 57.6% (44.07 – 70.39) in the CT arm. In eligible patients (RFA + CT; 57 pts, CT; 58 pts) these figures were 64.9% (95% CI, 51.13 – 77.09) and 56.9% (43.23 -69.84), respectively. The median PFS was 16.8 months in the RFA + CT arm (95% CI, 11.7-22.1) and 9.9 months (9.3-13.7) in the CT arm (p = 0.025). The number of patients with first recurrence at the RFA site only was 5 (9%). 4 more patients (7%) had a first recurrence at a RFA site in combination with a recurrence elsewhere in the liver. In total 11 lesions (in 9 pt) out of 170 lesions treated by RFA recurred locally at first progression (6.5%). Conclusion The EORTC CLOCC study is the first study that prospectively investigates the efficacy of RFA in combination with CT. The primary endpoint (30-months OS > 38%) was met, although also 30 months OS in the CT arm was much higher than 38%. RFA in combination with systemic therapy resulted in a significant prolongation of PFS of nearly 7 months. Local control of the lesions treated by RFA was high (93.5%). The study was not powered for OS. Longer follow-will have to be awaited to eventually assess the effect of RFA on OS. Disclosure All authors have declared no conflicts of interest.
Published Version
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