Systemic chemotherapy with doxorubicin, cisplatin and capecitabine for metastatic hepatocellular carcinoma

Park, Se Hoon; Lee, Yuna; Han, Sanghoon; Kwon, So Young; Kwon, Oh Sang; Kim, Sun Suk; Kim, Ju Hyun; Park, Yeon Ho; Lee, Jeong Nam; Bang, Soo Mee; Cho, Eun Kyung; Shin, Dong Bok; Lee, Jae Hoon

doi:10.1186/1471-2407-6-3

Cited by 81 publications

(60 citation statements)

References 27 publications

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“…Higher tumour response rates of 15 -25% were previously obtained with doxorubicin and cisplatin combinations with either capecitabine or UFT. However, this did not seem to affect significantly PFS and OS found to be less than 4 months and 8 months, respectively (Kim et al, 2006;Park et al, 2006a). A recent randomised phase III study comparing single agent doxorubicin vs PIAF regimen (cisplatin/ interferon a-2b/doxorubicin/fluorouracil) did not show any significant difference in OS between the two arms despite borderline statistical significance in favour of PIAF (6.8 and 8.7 months for doxorubicin and PIAF arms, respectively) (Yeo et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Multicentre phase II trial of capecitabine plus oxaliplatin (XELOX) in patients with advanced hepatocellular carcinoma: FFCD 03-03 trial

et al. 2007

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Evaluation of new drug combinations is needed to improve patients' prognosis in advanced hepatocellular carcinoma (HCC). The purpose of this study was to evaluate the safety and efficacy of the capecitabine -oxaliplatine combination (XELOX) in HCC patients. First-line chemotherapy with XELOX regimen consisting of a 3-week cycle of intravenous oxaliplatin (130 mg m À2 ) on Day 1, and oral capecitabine twice daily from Days 1 -14 (1000 mg m À2 ) was administered in patients with measurable, unresectable HCC. Fifty patients (male, 88%; median age, 68 years) received a total of 295 cycles (median, 6) of treatment. Disease control (three partial responses, 29 stable diseases) rate was 72% (95% CI 57 -83%). Median overall and median progression-free (PFS) survival was 9.3 months and 4.1 months, respectively. Progression-free survival rates at 6 and 12 months were 38% (95% CI 26 -52%) and 14% (95% CI 7 -26%), respectively. Main grade 3 -4 drug-related toxicities included diarrhoea (16%), elevation of aminotransferases and/or bilirubin (16%), thrombocytopenia (12%), and neurotoxicity (6%). Capecitabine plus oxaliplatin regimen showed modest anti-tumour activity with tolerable toxicities in patients with advanced HCC. However, the manageable toxicity profile and the encouraging disease control rate deserve further attention for this convenient, outpatient-based chemotherapy regimen.

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Section: Discussionmentioning

confidence: 99%

Multicentre phase II trial of capecitabine plus oxaliplatin (XELOX) in patients with advanced hepatocellular carcinoma: FFCD 03-03 trial

et al. 2007

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“…Adding capecitabine to doxorubicin and cisplatin also showed modest antitumor activity including 7 partial responses (24%) with the median PFS and median OS of 3.7 and 7.7 months, respectively (34).…”

Section: Doxorubicin Based Combination Chemotherapymentioning

confidence: 99%

Hepatocellular carcinoma (HCC): beyond sorafenib—chemotherapy

Kim

Talati

Kim

2017

J. Gastrointest. Oncol.

255

168

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Hepatocellular carcinoma (HCC) is the most common primary liver cancer with poor prognosis.The incidence of HCC and HCC-related deaths have increased over the last several decades. However, the treatment options for advanced HCC are very limited. Sorafenib remains the only drug approved for systemic treatment for advanced HCC. However, prior to sorafenib era conventional cytotoxic chemotherapies have been studied in advanced HCC. In this review, clinical studies of systemic chemotherapy for advanced HCC will be summarized and discussed.

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“…In fact, Dox was commonly used to treat HHC with two strategies. Firstly, Dox of 60 mg/m 2 was delivered as an intravenous infusion every 21 days but not exceed 500 mg/ m 2 (Park et al 2006;Uhm et al 2009). Secondly, Dox was directly delivered into tumors by drug eluting beads or liposome.…”

Section: Discussionmentioning

confidence: 99%

Doxorubicin and 5-fluorouracil resistant hepatic cancer cells demonstrate stem-like properties

Nguyen

Tran³

et al. 2012

Cytotechnology

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The efficacy of hepatocellular carcinoma (HCC) treatment is very low because of the high percentage of recurrence and resistance to anticancer agents. Hepatic cancer stem cells (HCSCs) are considered the origin of such recurrence and resistance. Our aim was to evaluate the stemness of doxorubicin and 5-fluorouracil resistant hepatic cancer cells and establish the new method to isolate the HCSCs from primary cultured HCC tumors. HCC biopsies were used to establish primary cultures. Then, primary cells were selected for HCSCs by culture in medium supplemented with doxorubicin (0, 0.1, 0.25, 0.5 or 1 lg/mL), 5-fluorouracil (0, 0.1, 0.25, 0.5 or 1 lg/mL) or their combination. Selection was confirmed by detection of HCSC markers such as CD133, CD13, CD90, and the side population was identified by rhodamine 123 efflux. The cell population with the strongest expression of these markers was used to evaluate the cell cycle, gene expression profile, tumor sphere formation, marker protein expression, and in vivo tumorigenesis. Selective culture of primary cells in medium supplemented with 0.5 lg/mL doxorubicin and 1 lg/mL 5-fluorouracil selected cancer cells with the highest stemness properties. Selected cells strongly expressed CD13, CD133, CD90, and CD326, efflux rhodamine 123 and formed tumor spheres in suspension. Moreover, selected cells were induced to differentiate into cells with high expression of CD19 and AFP (alpha-fetoprotein), and importantly, could form tumors in NOD/SCID mice upon injection of 1 9 10 5 cells/mouse. Selective culture with doxorubicin and 5-fluorouracil will enrich HCSCs, is an easy method to obtain HCSCs that can be used to develop better therapeutic strategies for patients with HCC, and particularly HCSC-targeting therapy.

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Systemic chemotherapy with doxorubicin, cisplatin and capecitabine for metastatic hepatocellular carcinoma

Cited by 81 publications

References 27 publications

Multicentre phase II trial of capecitabine plus oxaliplatin (XELOX) in patients with advanced hepatocellular carcinoma: FFCD 03-03 trial

Multicentre phase II trial of capecitabine plus oxaliplatin (XELOX) in patients with advanced hepatocellular carcinoma: FFCD 03-03 trial

Hepatocellular carcinoma (HCC): beyond sorafenib—chemotherapy

Doxorubicin and 5-fluorouracil resistant hepatic cancer cells demonstrate stem-like properties

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