Metronomic Capecitabine in Advanced Hepatocellular Carcinoma Patients: A Phase II Study (original) (raw)
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Journal of Clinical Oncology
Purpose Metronomic capecitabine (MC) is a well-tolerated systemic treatment showing promising results in one retrospective study, as second-line therapy after sorafenib failure, in patients with hepatocellular carcinoma (HCC). Methods 117 patients undergoing MC were compared to 112 patients, eligible for this treatment, but undergoing best supportive care (BSC) after sorafenib discontinuation for toxicity or HCC progression. The two groups were compared for demographic and clinical features. A multivariate regression analysis was conducted to detect independent prognostic factors. To balance confounding factors between the two groups, a propensity score model based on independent prognosticators (performance status, neoplastic thrombosis, causes of sorafenib discontinuation and pre-sorafenib treatment) was performed. Results Patients undergoing MC showed better performance status, lower tumor burden, lower prevalence of portal vein thrombosis, and better cancer stage. Median (95% CI) post-sorafenib survival (PSS) was longer in MC than in BSC patients [9.5 (7.5-11.6) vs 5.0 (4.2-5.7) months (p < 0.001)]. Neoplastic thrombosis, cause of sorafenib discontinuation, pre-sorafenib treatment and MC were independent prognosticators. The benefit of capecitabine was confirmed in patients after matching with propensity score [PSS: 9.9 (6.8-12.9) vs. 5.8 (4.8-6.8) months, (p = 0.001)]. MC lowered the mortality risk by about 40%. MC achieved better results in patients who stopped sorafenib for adverse events than in those who progressed during it [
Cancer communications (London, England), 2018
Hepatocellular carcinoma (HCC) is one of the most frequent causes of cancer-related death. Sorafenib, a multitarget angiogenesis inhibitor, is an approved frontline treatment for advanced HCC in Western countries, although a complete response (CR) to treatment is infrequently reported. Capecitabine, an oral fluoropyrimidine, has been shown to be effect in both treatment-naïve patients and those previously treated with sorafenib. To date, however, only one case of sustained CR to metronomic capecitabine has been reported. We describe three cases of advanced HCC treated with metronomic capecitabine where a CR was obtained. In the first case, capecitabine was administered as first line therapy; in the second case, capecitabine was used after intolerance to sorafenib; while in the third case, capecitabine was administered after sorafenib failure. Capecitabine is a potentially important treatment option for patients with advanced HCC and may even represent a cure in certain cases.
Hepatitis Monthly, 2013
Introduction: Sorafenib, an oral multikinase inhibitor, is the only systemic agent proven to be effective in patients with hepatocellular carcinoma (HCC). There are no approved second line systemic therapies in patients who have had disease progression on or are not eligible to sorafenib. Case Presentation: We describe two cases of unresectable HCC that were treated with low, "metronomic" doses of capecitabine. In the first patient, capecitabine was used after sorafenib failure. In the second case, treatment with capecitabine was attempted since the patient was considered not eligible for sorafenib due to spontaneous hepatic bleeding of a large HCC lesion. Treatment was effective and well tolerated in both patients with long-lasting objective responses. Conclusions: Lacking established second-line therapy, metronomic capecitabine may be a valid alternative in the treatment of HCC patients who are judged not eligible for sorafenib or those having progression disease on sorafenib.
To widen the setting of cancer patients who could benefit from metronomic capecitabine
Cancer Chemotherapy and Pharmacology, 2009
Purpose We investigated the eYcacy and toxicity of metronomic capecitabine administered at a Wxed dose of 1,000 mg daily in three elderly or poor performance status patients with advanced colorectal cancer (CRC) and gastric cancer. Methods In this study a pretreated advanced CRC patient (patient 1), a not previously treated advanced gastric cancer patient (patient 2), and a not previously treated advanced rectal cancer patient (patient 3) were given metronomic capecitabine administered at a Wxed dose of 1,000 mg daily (day 1-28 continuously). The eYcacy was evaluated every 3 months by instrumental evaluation and the treatment was continued until progression of disease or toxicity. Results A stable disease was observed in all three patients. The duration of treatment was above 3 months and no major toxicities occurred. Conclusions Our results indicate that metronomic capecitabine may be considered a safe and valid treatment option for advanced CRC and gastric cancer patients, both after failure of previous lines of chemotherapy or in front-line when standard chemotherapy is contraindicated, especially when the aim of medical treatment is to achieve disease control and to arrest tumour growth without aVecting the patient's quality of life. Nevertheless, further clinical studies, as well as a greater clinical experience are required in order to better deWne the role of this strategy in medical oncology.
Metronomic capecitabine as second-line treatment in hepatocellular carcinoma after sorafenib failure
Digestive and Liver Disease, 2015
Purpose Metronomic capecitabine (MC) is a well-tolerated systemic treatment showing promising results in one retrospective study, as second-line therapy after sorafenib failure, in patients with hepatocellular carcinoma (HCC). Methods 117 patients undergoing MC were compared to 112 patients, eligible for this treatment, but undergoing best supportive care (BSC) after sorafenib discontinuation for toxicity or HCC progression. The two groups were compared for demographic and clinical features. A multivariate regression analysis was conducted to detect independent prognostic factors. To balance confounding factors between the two groups, a propensity score model based on independent prognosticators (performance status, neoplastic thrombosis, causes of sorafenib discontinuation and pre-sorafenib treatment) was performed. Results Patients undergoing MC showed better performance status, lower tumor burden, lower prevalence of portal vein thrombosis, and better cancer stage. Median (95% CI) post-sorafenib survival (PSS) was longer in MC than in BSC patients [9.5 (7.5-11.6) vs 5.0 (4.2-5.7) months (p < 0.001)]. Neoplastic thrombosis, cause of sorafenib discontinuation, pre-sorafenib treatment and MC were independent prognosticators. The benefit of capecitabine was confirmed in patients after matching with propensity score [PSS: 9.9 (6.8-12.9) vs. 5.8 (4.8-6.8) months, (p = 0.001)]. MC lowered the mortality risk by about 40%. MC achieved better results in patients who stopped sorafenib for adverse events than in those who progressed during it [
Durable complete response of hepatocellular carcinoma after metronomic capecitabine
Tumori
Hepatocellular carcinoma (HCC) is a highly vascular tumor which is poorly responsive to standard systemic chemotherapy. Recently, various antiangiogenic targeted agents have shown promising activity at different levels of evidence in patients with advanced HCC, suggesting that such treatments might be effective. Since chemotherapy administered with metronomic schedules inhibits angiogenesis, we treated a 64-year-old man with advanced HCC with metronomic capecitabine. After only two months of treatment the HCC nodules disappeared on ultrasonography. This finding was confirmed by a computed tomography scan. After more than three years the patient is still in treatment with minimal toxicity and maintains a complete remission. Our case report suggests that metronomic capecitabine may be effective in advanced HCC patients while being also well tolerated. This is important, given the frequent comorbidities of HCC patients.
Metronomic capecitabine versus doxorubicin in advanced hepatocellular carcinoma
Korean Journal of Clinical Oncology, 2016
Purpose: We evaluated oral metronomic capecitabine (MC) compared to intravenous doxorubicin in patients with advanced or metastatic hepatocellular carcinoma (HCC). Methods: From January 2013 to December 2015, patients with Child-Pugh class A or early B were randomized either to MC group (500 mg twice daily continuously) or doxorubicin group (60 mg∕m 2 every 21 days). Results: Forty patients were included in each group. The baseline clinical characteristics of the enrolled patients were well balanced between the two groups. No complete response (CR) was reported in either group. In MC group, 2 patients (5%) had partial response (PR), 25 patients (62.5%) stable disease (SD) and 27 patients (67.5%) had disease control. In doxorubicin group, 4 patients (10%) achieved PR, 24 patients (60%) SD and 28 patients (70%) had disease control. The 6 months overall survival (OS) was 77.5% for MC and 75% for doxorubicin. The one year OS was 47.5% for MC and 42.5% for doxorubicin (P= 0.521). The median OS survival was 10.2 months for MC and 9.6 months for doxorubicin (95% confidence interval, 3.2-6.5). The 6 month progression-free survival (PFS) was 45% for MC and 50% for doxorubicin. The one year PFS was 12.5% for MC and 7.5% for doxorubicin (P= 0.289). The median time to progression was 3.4 months for MC and 3.1 months for doxorubicin. On multivariate analysis no significant impact for tumor stage, previous transhepatic arterial chemoembolization, portal vein thrombosis or median baseline alpha fetoprotein on OS. Conclusion: MC showed response rate and survival outcome comparable to doxorubicin in advanced HCC but with a more favorable toxicity profile.
Scientific Reports
The management of recurrent hepatocellular carcinoma untreatable with surgical options is based on systemic therapy with sorafenib. Due to the high rates of adverse events connected to the therapy with sorafenib, metronomic capecitabine seems a promising strategy for these patients. We analyzed the data of 38 patients with hepatocellular carcinoma recurrent after liver transplantation performed at our center. We compared the outcome of 17 patients receiving metronomic capecitabine versus 20 patients experiencing best supportive care and versus the data of the literature about treatment with sorafenib. In the group treated with metronomic capecitabine we observed an increased survival after tumor recurrence at the univariate and multivariate analysis compared to the group of best supportive care (median 22 months vs. 7 months, p < 0.01). Data from the literature on the use of sorafenib showed outcomes like our study group, with similar patient and tumoral features. The episodes of acute rejection and the tumor stage at the recurrence showed a correlation with patient survival at the univariate analysis. The metronomic capecitabine for hepatocellular cancer recurrent after liver transplantation seems effective without important adverse events and comparable results to sorafenib.