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TACE with dicycloplatin in patients with unresectable hepatocellular carcinoma: a multicenter randomized phase II trial

  • Oncology
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Abstract

Objectives

To investigate the efficacy and safety of dicycloplatin as chemotherapeutic regimen in transcatheter arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC).

Methods

In this randomized, open-label, phase II trial, patients with unresectable HCC who were TACE treatment–naïve or experienced recurrence after surgical resection or ablation were enrolled at 7 centers in China from March 2019 to November 2019. Participants were randomly assigned (1:1:1) to receive TACE with chemotherapeutic regimen of dicycloplatin alone (group A1), dicycloplatin plus epirubicin (group A2), or epirubicin alone (group B). The primary endpoint was objective response rate (ORR). The secondary endpoints included disease control rate (DCR), duration of response (DOR), progression-free survival (PFS), and safety.

Results

The ORR at 6 months in group A1 (n = 22) was significantly better than that in group B (p = 0.093; 90% confidence interval [CI], 1.03–9.45). The DCR in group A1 was significantly higher than that in group B (p = 0.045; 90% CI, 1.29–12.88). There was no significant difference in DOR among the groups (p = 0.271). The median PFS were 6.00 and 3.05 months in groups A2 (n = 25) and B (n = 24), respectively (p = 0.061). Grade 3 or worse adverse events were similar among groups in the safety population (p = 0.173).

Conclusion

TACE with dicycloplatin was comparably safe and well tolerable as epirubicin alone in patients with unresectable HCC. Compared with epirubicin alone, significant improvement in ORR and DCR when dicycloplatin was applied, as well as prolonged PFS when dicycloplatin plus epirubicin was applied, was generated.

Key Points

• To our knowledge, this is the first multicenter randomized trial to assess the efficacy and safety of TACE with dicycloplatin in patients with unresectable HCC.

• This phase II trial showed that TACE with dicycloplatin alone or plus epirubicin was comparably safe and well tolerable as epirubicin alone.

• Significant improvements in ORR, DCR when dicycloplatin was applied, and prolonged PFS when dicycloplatin plus epirubicin was applied were recorded compared with epirubicin alone.

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Abbreviations

ALT:

Glutamic pyruvic transaminase

AST:

Glutamic oxaloacetic transaminase

CR:

Complete response

DCR:

Disease control rate

DOR:

Duration of response

HCC:

Hepatocellular carcinoma

IQR:

Interquartile range

mRECIST:

Modified Response Evaluation Criteria in Solid Tumors

ORR:

Objective response rate

PD:

Progressive disease

PFS:

Progression-free survival

PR:

Partial response

PS:

Performance status

SD:

Stable disease

TACE:

Transarterial chemoembolization

References

  1. Llovet JM, Kelley RK, Villanueva A et al (2021) Hepatocellular carcinoma. Nat Rev Dis Primers 7:6

    Article  Google Scholar 

  2. Llovet JM, Real MI, Montana X et al (2002) Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomised controlled trial. Lancet 359:1734–1739

    Article  Google Scholar 

  3. Lo CM, Ngan H, Tso WK et al (2002) Randomized controlled trial of transarterial lipiodol chemoembolization for unresectable hepatocellular carcinoma. Hepatology 35:1164–1171

    Article  CAS  Google Scholar 

  4. Park JW, Chen M, Colombo M et al (2015) Global patterns of hepatocellular carcinoma management from diagnosis to death: the BRIDGE Study. Liver Int 35:2155–2166

    Article  Google Scholar 

  5. Zhou J, Sun H, Wang Z et al (2020) Guidelines for the diagnosis and treatment of hepatocellular carcinoma (2019 edition). Liver Cancer 9:682–720

    Article  Google Scholar 

  6. Marrero JA, Kulik LM, Sirlin CB et al (2018) Diagnosis, staging, and management of hepatocellular carcinoma: 2018 practice guidance by the American Association for the Study of Liver Diseases. Hepatology 68:723–750

    Article  Google Scholar 

  7. European Association for the Study of the Liver (2018) EASL Clinical Practice Guidelines:Management of hepatocellular carcinoma. J Hepatol 69:182–236

  8. Omata M, Cheng AL, Kokudo N et al (2017) Asia-Pacific clinical practice guidelines on the management of hepatocellular carcinoma: a 2017 update. Hepatol Int 11:317–370

    Article  Google Scholar 

  9. Basile A, Carrafiello G, Ierardi AM, Tsetis D, Brountzos E (2012) Quality-improvement guidelines for hepatic transarterial chemoembolization. Cardiovasc Intervent Radiol 35:765–774

    Article  Google Scholar 

  10. Chen LT, Martinelli E, Cheng AL et al (2020) Pan-Asian adapted ESMO Clinical Practice Guidelines for the management of patients with intermediate and advanced/relapsed hepatocellular carcinoma: a TOS-ESMO initiative endorsed by CSCO, ISMPO, JSMO, KSMO, MOS and SSO. Ann Oncol 31:334–351

    Article  Google Scholar 

  11. Guo T, Wu P, Liu P et al (2018) Identifying the best anticancer agent combination in TACE for HCC patients: a network meta-analysis. J Cancer 9:2640–2649

    Article  Google Scholar 

  12. Ikeda M, Kudo M, Aikata H et al (2018) Transarterial chemoembolization with miriplatin vs. epirubicin for unresectable hepatocellular carcinoma: a phase III randomized trial. J Gastroenterol 53:281–290

    Article  CAS  Google Scholar 

  13. Harper BW, Krause-Heuer AM, Grant MP, Manohar M, Garbutcheon-Singh KB, Aldrich-Wright JR (2010) Advances in platinum chemotherapeutics. Chemistry 16:7064–7077

    Article  CAS  Google Scholar 

  14. Zalba S, Garrido MJ (2013) Liposomes, a promising strategy for clinical application of platinum derivatives. Expert Opin Drug Deliv 10:829–844

    Article  CAS  Google Scholar 

  15. Wheate NJ, Walker S, Craig GE, Oun R (2010) The status of platinum anticancer drugs in the clinic and in clinical trials. Dalton Trans 39:8113–8127

    Article  CAS  Google Scholar 

  16. Goncalves MS, Silveira AF, Teixeira AR, Hyppolito MA (2013) Mechanisms of cisplatin ototoxicity: theoretical review. J Laryngol Otol 127:536–541

    Article  CAS  Google Scholar 

  17. Qaddoumi I, Bass JK, Wu J et al (2012) Carboplatin-associated ototoxicity in children with retinoblastoma. J Clin Oncol 30:1034–1041

    Article  CAS  Google Scholar 

  18. Yu JJ, Yang X, Song Q, Mueller MD, Remick SC (2014) Dicycloplatin, a novel platinum analog in chemotherapy: synthesis of Chinese pre-clinical and clinical profile and emerging mechanistic studies. Anticancer Res 34:455–463

    CAS  Google Scholar 

  19. Yu JJ, Hogan T, Morley C et al (2019) Adverse effects profile of dicycloplatin (DCP) offers chemotherapeutic advantage over cisplatin and carboplatin. Anticancer Res 39:4455–4462

    Article  CAS  Google Scholar 

  20. Yang X, Zheng J, Song Q et al (2015) Determination methods for the anticancer drug dicycloplatin, a supramolecule assembled through hydrogen bonding. Analyst 140:2704–2712

    Article  CAS  Google Scholar 

  21. Li GQ, Chen XG, Wu XP et al (2012) Effect of dicycloplatin, a novel platinum chemotherapeutical drug, on inhibiting cell growth and inducing cell apoptosis. PLoS One 7:e48994

  22. Liu KJ, Guan ZZ, Liang Y et al (2014) A double-blind, randomized phase II study of dicycloplatin plus paclitaxel versus carboplatin plus paclitaxel as first-line therapy for patients with advanced non-small-cell lung cancers. Arch Med Sci 10:717–724

    Article  Google Scholar 

  23. Zhao D, Zhang Y, Xu C et al (2012) Pharmacokinetics, tissue distribution, and plasma protein binding study of platinum originating from dicycloplatin, a novel antitumor supramolecule, in rats and dogs by ICP-MS. Biol Trace Elem Res 148:203–208

    Article  CAS  Google Scholar 

  24. Lu J, Zhong BY, Zhu HD, Guo JH, Teng GJ (2019) Embolotherapy of unresectable hepatocellular carcinoma: eastern perspective. Chin Clin Oncol 8:60

    Article  Google Scholar 

  25. Sahara S, Kawai N, Sato M et al (2012) Prospective evaluation of transcatheter arterial chemoembolization (TACE) with multiple anti-cancer drugs (epirubicin, cisplatin, mitomycin c, 5-fluorouracil) compared with TACE with epirubicin for treatment of hepatocellular carcinoma. Cardiovasc Intervent Radiol 35:1363–1371

    Article  Google Scholar 

  26. Sahara S, Kawai N, Sato M et al (2010) Prospective comparison of transcatheter arterial chemoembolization with lipiodol-epirubicin and lipiodol-cisplatin for treatment of recurrent hepatocellular carcinoma. Jpn J Radiol 28:362–368

    Article  CAS  Google Scholar 

  27. Park JW, Amarapurkar D, Chao Y et al (2013) Consensus recommendations and review by an International Expert Panel on Interventions in Hepatocellular Carcinoma (EPOIHCC). Liver Int 33:327–337

    Article  CAS  Google Scholar 

  28. Yamanaka K, Hatano E, Narita M et al (2011) Comparative study of cisplatin and epirubicin in transcatheter arterial chemoembolization for hepatocellular carcinoma. Hepatol Res 41:303–309

    Article  CAS  Google Scholar 

  29. Homma H, Mezawa S, Doi T et al (2004) A comparative randomized trial of intermittent intrahepatic arterial carboplatin- versus doxorubicin-lipiodol emulsion in advanced hepatocellular carcinoma (stage IV). Hepatogastroenterology 51:1135–1139

    CAS  Google Scholar 

  30. Apps MG, Choi EH, Wheate NJ (2015) The state-of-play and future of platinum drugs. Endocr Relat Cancer 22:R219–R233

    Article  CAS  Google Scholar 

  31. Zhao M, Xiang P, Jiang H (2018) Transarterial chemoembolization (TACE) with platinum versus anthracyclines for hepatocellular carcinoma: a meta-analysis. Int J Surg 53:151–158

    Article  Google Scholar 

  32. Li S, Huang H, Liao H et al (2013) Phase I clinical trial of the novel platin complex dicycloplatin: clinical and pharmacokinetic results. Int J Clin Pharmacol Ther 51:96–105

    Article  CAS  Google Scholar 

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Acknowledgements

We thank the patients and their families for participating in this trial.

Funding

The funders of the study (Beijing Suopuxingda Pharmaceutical Research Co., Ltd.) had no role in study protocol design, data analysis and interpretation, or writing of the report.

Author information

Author notes

  1. Hai-Dong Zhu and Xiao Li contributed equally as the joint first authors.

Authors and Affiliations

  1. Center of Interventional Radiology & Vascular Surgery, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, 87 Dingjiaqiao Road, Nanjing, 210009, China

    Hai-Dong Zhu, Jian Lu, Chu-Hui Zeng & Gao-Jun Teng

  2. Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China

    Xiao Li & Zheng-Qiang Yang

  3. Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, Lishui Hospital of Zhejiang University, Lishui, 323000, China

    Jian-Song Ji & Jian-Fei Tu

  4. Department of Minimally Invasive Interventional Radiology, Yunnan Tumor Hospital, the Third Affiliated Hospital of Kunming Medical University, Kunming, 650106, China

    Ming Huang & Jin-Mei Zhou

  5. Department of Radiology, Cancer Hospital Affiliated to University of Chinese Academy of Sciences, Hangzhou, 310022, China

    Guo-Liang Shao

  6. Department of Interventional Radiology, Guizhou Cancer Hospital, Cancer Hospital of Guizhou Medical University, Guiyang, 550000, China

    Xu-Ya Zhao

  7. Department of Intervention Radiology, Henan Cancer Hospital, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, 450008, China

    Hai-Liang Li

Authors
  1. Hai-Dong Zhu
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  2. Xiao Li
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  6. Jian Lu
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  13. Gao-Jun Teng
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Corresponding author

Correspondence to Gao-Jun Teng.

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Conflict of interest

The authors declare no competing interests.

Informed consent

Written informed consent was obtained from all trial participants included in the study.

Ethical approval

Institutional Review Board approval was obtained.

Methodology

• Prospective

• Interventional

• Performed at seven institution

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Zhu, HD., Li, X., Ji, JS. et al. TACE with dicycloplatin in patients with unresectable hepatocellular carcinoma: a multicenter randomized phase II trial. Eur Radiol 32, 7335–7343 (2022). https://doi.org/10.1007/s00330-022-08848-7

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  • DOI: https://doi.org/10.1007/s00330-022-08848-7

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