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 ae 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.

Walter, I., Schulz, U., Vogelhuber, M., Wiedmann, K., Endlicher, E., Klebl, F., et al. (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), 192 [10.1007/s12032-017-1040-0].

Communicative reprogramming non-curative hepatocellular carcinoma with low-dose metronomic chemotherapy, COX-2 inhibitor and PPAR-gamma agonist: a phase II trial

Ghibelli L.;
2017-01-01

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 ae 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.
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore BIO/13
English
Anakoinosis; Biomodulatory therapy; COX-2 inhibitor; Hepatocellular carcinoma; Metronomic low-dose chemotherapy; Pioglitazone; Administration, Metronomic; Aged; Antineoplastic Combined Chemotherapy Protocols; C-Reactive Protein; Capecitabine; Carcinoma, Hepatocellular; Cyclooxygenase 2 Inhibitors; Disease-Free Survival; Female; Humans; Lactones; Liver Neoplasms; Male; Middle Aged; PPAR gamma; Pioglitazone; Sulfones; Thiazolidinediones; Treatment Outcome; alpha-Fetoproteins
Walter, I., Schulz, U., Vogelhuber, M., Wiedmann, K., Endlicher, E., Klebl, F., et al. (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), 192 [10.1007/s12032-017-1040-0].
Walter, I; Schulz, U; Vogelhuber, M; Wiedmann, K; Endlicher, E; Klebl, F; Andreesen, R; Herr, W; Ghibelli, L; Hackl, C; Wiest, R; Reichle, A
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/241855
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