Oxaliplatin/5-Fluorouracil in Advanced Hepatocellular Carcinoma: Case Report and Single-Center Retrospective Review

Goldstein, Robert M.; Yu, Dominic; Gillmore, Roopinder; Thirlwell, Christina; O'Donoghue, P; Mayer, Astrid; Meyer, Tim

doi:10.2217/fon.14.108

Cited by 9 publications

(8 citation statements)

References 20 publications

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“…The median OS of 8 months in the present study is longer than that in Goldstein’s (median OS: 6.3 months) and Ogasawara’s (median OS: 7.2 months) reported for patients with sorafenib-refractory advanced HCC. 21,22 That is also longer than that of Asia-Pacific trial (median OS: 6.5 months). 6 Especially for the patients with lower liver tumor burden, extrahepatic metastasis, and had a PR to apatinib, the median OS reached to 16 months, 18 months, and 19 months, respectively, which is significantly longer than that of other studies.…”

Section: Discussionmentioning

confidence: 90%

“…Although some cytotoxic chemotherapies and targeted therapies, such as capecitabine, Leucovocin and oxaliplatin (FOLFOX), epirubicin, cisplatin, and cetuximab, are also used in the treatment of sorafenib-refractory advanced HCC, associated morbidities, such as neutropenia, thrombocytopenia, and gastrointestinal toxicity, frequently occur. 20 –22 More serious toxicities, including cytotoxicity-related neutropenic sepsis and liver injury, have also been reported after treatment. 21 However, in the present study, patients treated with apatinib for sorafenib-refractory HCC did not experience treatment-related death.…”

Section: Discussionmentioning

confidence: 99%

“…Although some treatments have been reported for patients with sorafenib-refractory HCC, some of the adverse events were severe and offset the moderate beneficial effects. 20 –22 Recently, 2 case reports showed that apatinib demonstrated an excellent antitumor effect in patients with sorafenib-refractory HCC. 14,16 Therefore, we conducted a pilot study to investigate apatinib use for patients with sorafenib-refractory advanced HCC (sorafenib-refractory HCC was defined as a target lesion with 2 successive instances of progression, determined using modified response evaluation criteria in solid tumors [mRECIST] 23 every month after initiation of sorafenib treatment) to evaluate the safety and effectiveness of apatinib in these patients.…”

Section: Introductionmentioning

confidence: 99%

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Apatinib for Patients With Sorafenib-Refractory Advanced Hepatitis B Virus Related Hepatocellular Carcinoma: Results of a Pilot Study

et al. 2019

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More than half of the patients with advanced hepatocellular carcinoma (HCC) do not respond to primary treatment with sorafenib. Currently, there are no universally accepted methods for further treatment. This pilot study was performed to assess the safety and effectiveness of apatinib as an optional treatment for patients with sorafenib-refractory HCC. Between January 2015 and May 2017, 43 consecutive patients with sorafenib-refractory advanced HCC who received apatinib were reviewed. The objective response rate (ORR) and disease control rate (DCR) were assessed using modified response evaluation criteria in solid tumors. The time to progression (TTP) and overall survival (OS) were determined using the Kaplan-Meier method. Toxicities associated with apatinib were assessed. All patients had hepatitis B virus (HBV) related HCC. The mean follow-up time was 11 months (range: 3-37) and the mean duration of apatinib was 7.6 months (range: 1-32). After treatment, 11 patients had partial response (PR), 18 had stable disease (SD), and 14 had progressive disease (PD); accordingly, the ORR and DCR were 25.6% and 67.4%, respectively. The median TTP and OS were 3 months (95% confidence interval [CI]: 1.9-4.1) and 8 months (95% CI: 6.9-9.0), respectively. The median OS times for PR, SD, and PD were 19 months (95% CI: 15.8-22.2), 8 months (95% CI: 7.3-8.7), and 4 months (95% CI: 3.1-4.9), respectively ( P < .001). The median TTP for PR, SD, and PD was 14 months (95% CI: 11.9-16.1), 3 months (95% CI: 2.3-3.7) and 1 month, respectively ( P < .001). No patients experienced toxicity-related death. The most common toxicities were weight loss, hand–foot skin reaction, and hypertension. Twelve adverse events of grade 3 or higher were observed. Based on our findings, apatinib is a promising treatment for patients with sorafenib-refractory advanced HBV-related HCC.

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Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Apatinib for Patients With Sorafenib-Refractory Advanced Hepatitis B Virus Related Hepatocellular Carcinoma: Results of a Pilot Study

et al. 2019

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“… 10 The ORR was also higher than those reports in patients with sorafenib-refractory HCC. 27 – 29 The most likely explanation for the improvement of survival outcomes by apatinib treatment among patients with sorafenib-resistant HCC may be the antitumor angiogenic actions of apatinib that occur via its selective inhibition of VEGFR-2, with a binding affinity that is 10 times higher than that of sorafenib. 15 , 16 In contrast, because its anti-VEGFR2 ability is one-tenth that of apatinib, sorafenib is inefficient against sorafenib-resistant HCC.…”

Section: Discussionmentioning

confidence: 99%

Apatinib treatment may improve survival outcomes of patients with hepatitis B virus-related sorafenib-resistant hepatocellular carcinoma

et al. 2020

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Aims: This study aimed to (a) assess the effectiveness and safety of apatinib as a subsequent treatment for patients with sorafenib-resistant hepatocellular carcinoma (HCC), and (b) identify the clinical factors influencing their treatment outcomes. Methods: The electronic medical records of consecutive patients with newly diagnosed advanced HCC treated with first-line sorafenib from 2015 to 2017 were retrospectively reviewed. Patients who were confirmed to have primary resistance to sorafenib were enrolled in this study. The outcomes of patients treated with apatinib were compared with those of patients who received supportive care. The primary endpoint was overall survival (OS). Results: A total of 92 patients with sorafenib-resistant advanced HCC (84 men and 8 women; mean age, 51.9 years) were included. All patients had an etiology of hepatitis B. The median OS in the overall cohort was 5.0 months [95% confidence interval (CI): 3.9, 6.0]. Of 92 patients, 58 (63.0%) were treated with apatinib, and 34 (37.0%) received supportive care. Apatinib treatment was associated with longer survival times than supportive care for patients with sorafenib-resistant advanced HCC (median OS: 7.0 versus 4.0 months, p < 0.001). The results of the multivariate analysis demonstrated that liver tumor load [hazard ratio (HR): 3.653, 95% CI: 2.047, 5.965, p < 0.001] and extrahepatic spread (HR: 0.303, 95% CI: 0.231, 0.778, p = 0.003) were independent predictors of OS after apatinib treatment. Conclusion: This study showed that subsequent apatinib treatment may improve survival outcomes compared with supportive care for patients with sorafenib-resistant, advanced hepatitis B virus (HBV)-related HCC, especially for patients who have a lower liver tumor load and extrahepatic spread.

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“…To date, 5-FU is still being widely used for the treatment of advanced HCC [ 4 ]. Unfortunately, success of a single or combination chemotherapy regimen is mostly transient and modest [ 21 , 22 ]. The present study showed that the combination of AZD8055, but not of everolimus, with 5-FU significantly decreased tumor cell viability compared with single-drug treatment.…”

Section: Discussionmentioning

confidence: 99%

Targeting mTORC1/2 Complexes Inhibit Tumorigenesis and Enhance Sensitivity to 5-Flourouracil (5-FU) in Hepatocellular Carcinoma: A Preclinical Study of mTORC1/2-Targeted Therapy in Hepatocellular Carcinoma (HCC)

et al. 2018

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BackgroundAlthough 5-Flourouracil(5-FU) is used as the first-choice treatment for advanced hepatocellular carcinoma (HCC), it is associated with acquired and intrinsic resistance. Hyperactivation of mTOR signaling has been linked to tumorigenesis and chemoresistance in HCC. The aim of this study was to evaluate and compare the antitumor effects of mTORC1 inhibitor everolimus and mTORC1/2 inhibitor AZD8055 and to examine the interaction between 5-FU and mTORC1/2 inhibitor in HCC.Material/MethodsUsing cultured HCC cells and mouse xenograft, the antitumor effects of everolimus and AZD8055 were analyzed as mono- and combination therapy with 5-Flourouracil.ResultsTSC2-deficient HCC cell lines were more sensitive to everolimus and AZD8055. AZD8055, but not everolimus, potently prevented cells from transitioning from G1 phase to S phase in TSC2-high-expressing HCC cells. AZD8055 reduced phosphorylation of both mTORC1 and mTORC2 substrates. In contrast, everolimus reduced the phosphorylation of mTORC1 substrates, but increased the phosphorylation of AKT. Notably, AZD8055, but not everolimus, synergistically enhanced the efficacy of 5-FU via reversing 5-FU-induced upregulation of P-glycoprotein (P-gp). The synergistic antitumor effect of AZD8055 and 5-FU was also observed in a HCC xenograft mouse model.ConclusionsTSC2 in HCC is a promising efficacy-predicting biomarker for the treatment of mTORC1/2 inhibitor. AZD8055 showed stronger antitumor activity than everolimus in TSC2-high-expressing HCC cells. Moreover, the combination of mTORC1/2 inhibitor with 5-FU appears to be a promising option for HCC patients refractory to chemotherapy.

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Oxaliplatin/5-Fluorouracil in Advanced Hepatocellular Carcinoma: Case Report and Single-Center Retrospective Review

Abstract: In advanced hepatocellular carcinoma, FOLFOX can induce clinically relevant responses, but needs prospective validation.

Cited by 9 publications

References 20 publications

Apatinib for Patients With Sorafenib-Refractory Advanced Hepatitis B Virus Related Hepatocellular Carcinoma: Results of a Pilot Study

Apatinib for Patients With Sorafenib-Refractory Advanced Hepatitis B Virus Related Hepatocellular Carcinoma: Results of a Pilot Study

Apatinib treatment may improve survival outcomes of patients with hepatitis B virus-related sorafenib-resistant hepatocellular carcinoma

Targeting mTORC1/2 Complexes Inhibit Tumorigenesis and Enhance Sensitivity to 5-Flourouracil (5-FU) in Hepatocellular Carcinoma: A Preclinical Study of mTORC1/2-Targeted Therapy in Hepatocellular Carcinoma (HCC)

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