Abstract
Some patients with advanced hepatocellular carcinoma (HCC) progressing under sorafenib remain eligible for further systemic therapy. Little is known on the feasibility of systemic treatment beyond sorafenib in this setting. Consecutive HCC patients pre-treated with sorafenib received gemcitabine 1,000 mg/m² and oxaliplatin 100 mg/m² every 14 days. Exclusion criteria included Child C cirrhosis, PS ≥ 3, creatinine clearance <20 ml/min, albumin <25 g/L and bilirubin > 54 μmol/L. Pre-treatment body composition was evaluated by CT scan to detect muscle wasting (sarcopenia). The primary evaluation criterion was safety. Secondary evaluation criteria were response rate, and progression-free (PFS) and overall survival (OS). Eighteen patients (median age: 64 years, range 25–77) received a total of 90 cycles (median per patient: 4, range 1–16). Eight patients (44.4 %) had a PS of 2, 5 (27.8 %) had Child-Pugh B cirrhosis and 13 (72.2 %) had a CLIP score >3. The most frequent toxicities were thrombocytopenia (grade 2–4: n = 7, 38.9 %) and peripheral neuropathy (grade 2–3: n = 7, 38.9 %). The overall response rate was 18.8 % (95 % CI: 0–37.9), and another 18.8 % of patients had stable disease. The median PFS and OS were 3.2 (95 % CI: 2.3–3.9) and 4.7 (95 % CI: 3.8–8.1) months, respectively. Overall survival was significantly longer in patients without sarcopenia [10.0 months (95 % CI: 7.0–13.8) vs. 3.0 months (95 % CI: 2.5–3.9), p < 0.001] and in patients with an ECOG PS < 2 [8.1 months (95 % CI: 7.0–13.8) vs. 3.8 months (95 % CI: 2.5–3.9), p = 0.017]. In our experience, gemcitabine–oxaliplatin was feasible and had detectable clinical activity in HCC patients pre-treated with sorafenib. Further studies are needed to confirm these findings.
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The authors wish to thank the nurses, residents and clinical research staff of the Cochin Teaching Hospital.
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Prof. Goldwasser has acted as paid consultant for Bayer Healthcare and Pfizer. Dr. Ropert has acted as paid consultant for Bayer Healthcare and Sanofi-Aventis. Dr. Mir and Dr. Coriat have acted as paid consultants for Roche. The other authors have no conflict of interest to declare.
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The authors Olivier Mir and Romain Coriat contributed equally to this work.
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Mir, O., Coriat, R., Boudou-Rouquette, P. et al. Gemcitabine and oxaliplatin as second-line treatment in patients with hepatocellular carcinoma pre-treated with sorafenib. Med Oncol 29, 2793–2799 (2012). https://doi.org/10.1007/s12032-012-0208-x
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DOI: https://doi.org/10.1007/s12032-012-0208-x