Dataset Information

Metronomic capecitabine vs. best supportive care in Child-Pugh B hepatocellular carcinoma: a proof of concept.

ABSTRACT: There is a relative lack of evidence about systemic treatments in patients with hepatocellular carcinoma (HCC) and moderate liver dysfunction (Child-Pugh B). In this multicenter study we retrospectively analyzed data from Child-Pugh B-HCC patients naïve to systemic therapies, treated with MC or best supportive care (BSC). To reduce the risk of selection bias, an inverse probability of treatment weighting approach was adopted. Propensity score was generated including: extrahepatic spread; macrovascular invasion; performance status, alphafetoprotein?>?400?ng/ml, Child- Pugh score [B7 vs. B8-9]. We identified 35 MC-treated patients and 70 controls. Median overall survival was 7.5 [95% CI: 3.733-11.267]in MC-patients and 5.1 months [95% CI: 4.098-6.102] in the BSC group (p?=?0.013). In patients treated with MC, median progression-free survival was 4.5 months (95% CI: 2.5-6.5). The univariate unweighted Cox regression showed a 42% reduction in death risk for patients on MC (95%CI: 0.370-0.906; p?=?0.017). After weighting for potential confounders, death risk remained essentially unaltered. In the MC group, 12 patients (34.3%) experienced at least one adverse event, the most common of which were: fatigue (17.1%), hand-foot syndrome (8.5%), thrombocytopenia (8.5%), and neutropenia (5.7%). MC seems a safe option for Child-Pugh B-HCC patients. Its potential antitumour activity warrants prospective evaluations.

SUBMITTER: De Lorenzo S

PROVIDER: S-EPMC6030080 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Metronomic capecitabine vs. best supportive care in Child-Pugh B hepatocellular carcinoma: a proof of concept.

De Lorenzo Stefania S Tovoli Francesco F Barbera Maria Aurelia MA Garuti Francesca F Palloni Andrea A Frega Giorgio G Garajovà Ingrid I Rizzo Alessandro A Trevisani Franco F Brandi Giovanni G

Scientific reports 20180703 1

There is a relative lack of evidence about systemic treatments in patients with hepatocellular carcinoma (HCC) and moderate liver dysfunction (Child-Pugh B). In this multicenter study we retrospectively analyzed data from Child-Pugh B-HCC patients naïve to systemic therapies, treated with MC or best supportive care (BSC). To reduce the risk of selection bias, an inverse probability of treatment weighting approach was adopted. Propensity score was generated including: extrahepatic spread; macrova ...[more]

PMID: 29968763

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Project description:ImportanceAlthough oral metronomic chemotherapy is often used in progressive pediatric solid malignant tumors, a literature review reveals that only small single-arm retrospective or phase 1 and 2 studies have been performed. Skepticism abounds because of the lack of level 1 evidence.ObjectivesTo compare the effect of metronomic chemotherapy on progression-free survival (PFS) with that of placebo in pediatric patients with primary extracranial, nonhematopoietic solid malignant tumors that progress after at least 2 lines of chemotherapy.Design, setting, and participantsA double-blinded, placebo-controlled randomized clinical trial was conducted from October 1, 2013, through December 31, 2015, at the cancer center at All India Institute of Medical Sciences in children aged 5 to 18 years with primary extracranial, nonhematopoietic solid malignant tumors that progressed after at least 2 lines of chemotherapy and had no further curative options.InterventionsOne arm received a 4-drug oral metronomic regimen of daily celecoxib and thalidomide with alternating periods of etoposide and cyclophosphamide, whereas the other arm received placebo. Disease status was assessed at baseline, 9 weeks, 18 weeks, and 27 weeks or at clinical progression.Main outcomes and measuresThe primary end point was PFS as defined by the proportion of patients without disease progression at 6 months, and PFS duration and overall survival (OS) were secondary end points.ResultsA total of 108 of the 123 patients screened were enrolled, with 52 randomized to the placebo group (median age, 15 years; 40 male [76.9%]) and 56 to the metronomic chemotherapy group (median age, 13 years; 42 male [75.0%]). At a median follow-up of 2.9 months, 100% of the patients had disease progression by 6 months in the placebo group vs 96.4% in the metronomic chemotherapy group (P = .24). Median PFS and OS in the 2 groups was similar (hazard ratio [HR], 0.69; 95% CI, 0.47-1.03 [P = .07] for PFS; and HR, 0.74; 95% CI, 0.50-1.09 [P = .13] for OS). In post hoc subgroup analysis, cohorts receiving more than 3 cycles (HR for PFS, 0.46; 95% CI, 0.23-0.93; P = .03) and those without a bone sarcoma (ie, neither primitive neuroectodermal tumor nor osteosarcoma) (HR for PFS, 0.39; 95% CI, 0.18-0.81; P = .01) appeared to benefit from metronomic chemotherapy.Conclusions and relevanceMetronomic chemotherapy does not improve 6-month PFS, compared with placebo, among pediatric patients with extracranial progressive solid malignant tumors . However, patients without bone sarcoma and those able to tolerate therapy for more than 3 cycles (9 weeks) benefit.Trial registrationclinicaltrials.gov Identifier: NCT01858571.

Project description:ImportanceCapecitabine maintenance therapy improves survival outcomes in various cancer types, but data are limited on the efficacy and safety of capecitabine maintenance therapy in metastatic nasopharyngeal carcinoma (NPC).ObjectiveTo investigate the efficacy and safety of capecitabine maintenance therapy in metastatic NPC.Design, setting, and participantsThis randomized phase 3 clinical trial was conducted at Sun Yat-sen University Cancer Center from May 16, 2015, to January 9, 2020, among 104 patients with newly diagnosed metastatic NPC who had achieved disease control after 4 to 6 cycles of induction chemotherapy with paclitaxel, cisplatin, and capecitabine. The final follow-up date was May 30, 2021. All efficacy analyses were conducted in the intention-to-treat population.InterventionsEligible patients were randomly assigned (1:1) to receive either capecitabine maintenance therapy (1000 mg/m2 orally twice daily on days 1-14) every 3 weeks plus best supportive care (BSC) (capecitabine maintenance group) or BSC alone after 4 to 6 cycles of induction chemotherapy.Main outcomes and measuresProgression-free survival (PFS). Secondary end points were objective response rate, duration of response, overall survival, and safety.ResultsThis study included 104 patients (84 men [80.8%]; median age, 47 years [IQR, 38-54 years]), with 52 assigned to the capecitabine maintenance group and 52 assigned to the BSC group. After a median follow-up of 33.8 months (IQR, 22.9-50.7 months), there were 23 events (44.2%) of progression or death in the capecitabine maintenance group and 37 events (71.2%) of progression or death in the BSC group. Median PFS survival was significantly higher in the capecitabine maintenance group (35.9 months [95% CI, 20.5 months-not reached]) than in the BSC group (8.2 months [95% CI, 6.4-10.0 months]), with a hazard ratio of 0.44 (95% CI, 0.26-0.74; P = .002). Higher objective response rates and longer median duration of response were observed in the capecitabine maintenance group (25.0%; 40.0 months) compared with the BSC group (objective response rate, 25.0% [n = 13] vs 11.5% [n = 6]; and median duration of response, 40.0 months [95% CI, not reached-not reached] vs 13.2 months [95% CI, 9.9-16.5 months]). The most common grade 3 or 4 adverse events during maintenance therapy were anemia (6 of 50 [12.0%]), hand-foot syndrome (5 of 50 [10.0%]), nausea and vomiting (3 of 50 [6.0%]), fatigue (2 of 50 [4.0%]), and mucositis (2 of 50 [4.0%]). No deaths in the maintenance group were deemed treatment-related.Conclusions and relevanceIn this phase 3 randomized clinical trial, capecitabine maintenance therapy significantly improved PFS for patients with newly diagnosed metastatic NPC who achieved disease control after capecitabine-containing induction chemotherapy. Capecitabine exhibited manageable toxic effects.Trial registrationClinicalTrials.gov Identifier: NCT02460419.

Dataset Information

Metronomic capecitabine vs. best supportive care in Child-Pugh B hepatocellular carcinoma: a proof of concept.

Publications

Metronomic capecitabine vs. best supportive care in Child-Pugh B hepatocellular carcinoma: a proof of concept.

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