Communicative reprogramming non-curative hepatocellular carcinoma with low-dose metronomic chemotherapy, COX-2 inhibitor and PPAR-gamma agonist: a phase II trial
Walter I, Schulz U, Vogelhuber M, Wiedmann K, Endlicher E, Klebl F, Andreesen R, Herr W, Ghibelli L, Hackl C, Wiest R, Reichle A (2017)
Publication Type: Journal article
Publication year: 2017
Journal
Book Volume: 34
Article Number: 192
Journal Issue: 12
DOI: 10.1007/s12032-017-1040-0
Abstract
Systemic therapy for advanced hepatocellular carcinoma (HCC) is still challenging. A biomodulatory therapy approach targeting the communicative infrastructure of HCC, including metronomic low-dose chemotherapy with capecitabine, pioglitazone and rofecoxib, has been evaluated in patients with non-curative HCC. Altogether 38 patients were evaluable in this one-arm, multicenter phase II trial. The primary endpoint, median progression-free survival was 2.7 months (95% CI: 1.6–3.79) for all evaluable patients and 8.4 months (95% CI: 0–18.13) for patients ≥ 6 weeks on protocol. Median overall survival (OS) was 6.7 months (95% CI: 4.08–9.31) and 9.4 months (95% CI: 4.82–13.97), respectively. Most common adverse events were edemas grade 3, which were commonly related to the advanced stage, with 66% of the patients suffering from liver cirrhosis. Exploratory data analyses showed significant impact of ECOG performance status grade 0 versus 1 and CLIP score 0/1 versus > 1 on OS, 9.8 months (95% CI: 4.24–15.35) versus 2.7 months (95% CI: 1.03–4.36; P = 0.002), and 9.8 months (95% CI: 3.23–16.37) versus 4.4 months (95% CI: 3.14–5.66; P = 0.009), respectively. Preceding tumor surgery had significant beneficial impact on survival, as well as maximal tumor diameter of < 5 cm. The correlation of C-reactive protein decrease with significantly improved OS underlines the close link between inflammation and tumor control. Biomodulatory therapy in advanced HCC may be a low toxic, efficacious treatment and principally demonstrates that such approaches should be followed further for treatment of advanced HCC.
Involved external institutions
Universitätsklinikum Regensburg
Germany (DE)
Krankenhaus Barmherzige Brüder
Germany (DE)
Università degli Studi di Roma 'Tor Vergata'
Italy (IT)
Inselspital, Universitätsspital Bern
Switzerland (CH)
Germany (DE)
Krankenhaus Barmherzige Brüder
Germany (DE)
Università degli Studi di Roma 'Tor Vergata'
Italy (IT)
Inselspital, Universitätsspital Bern
Switzerland (CH)
How to cite
APA:
Walter, I., Schulz, U., Vogelhuber, M., Wiedmann, K., Endlicher, E., Klebl, F.,... Reichle, A. (2017). Communicative reprogramming non-curative hepatocellular carcinoma with low-dose metronomic chemotherapy, COX-2 inhibitor and PPAR-gamma agonist: a phase II trial. Medical Oncology, 34(12). https://doi.org/10.1007/s12032-017-1040-0
MLA:
Walter, I., et al. "Communicative reprogramming non-curative hepatocellular carcinoma with low-dose metronomic chemotherapy, COX-2 inhibitor and PPAR-gamma agonist: a phase II trial." Medical Oncology 34.12 (2017).
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