CUHK develops new anhydrous drug formulation for TACE, doubles progression-free survival period in patients with hepatocellular carcinoma
CU Medicine has developed a novel drug formulation based on conventional transarterial chemoembolisation, combining an anhydrous pure cisplatin powder with ethiodised oil to treat patients with hepatocellular carcinoma (HCC). Results from a clinical trial demonstrated that the new formulation is significantly better across all treatment outcome parameters compared with the conventional formulation, offering a new option for patients with intermediate-stage HCC.
(From left) Dr Lee Kit-fai, Clinical Associate Professor (Honorary) in the Department of Surgery at CU Medicine; Professor Simon Yu Chun-ho, Clinical Professor (Honorary) in the Department of Imaging and Interventional Radiology at CU Medicine; and Professor Stephen Chan Lam, Ip’s Family Trust Professor in Clinical Oncology and Professor of the Department of Clinical Oncology at CU Medicine.
Liver cancer is the third leading cause of cancer death and the fifth most common cancer in Hong Kong. The Department of Imaging and Interventional Radiology at The Chinese University of Hong Kong (CUHK)’s Faculty of Medicine (CU Medicine) has developed a novel drug formulation based on conventional transarterial chemoembolisation (cTACE), combining an anhydrous pure cisplatin powder with ethiodised oil (aTACE), to treat patients with hepatocellular carcinoma. Results from a clinical trial showed that all tumours were completely eliminated on imaging in 90% of patients after treatment, nearly double the rate achieved by cTACE. Progression-free survival was extended as much as twofold, and overall survival was prolonged by more than 17 months, highlighting the formula’s remarkable tumour eradication efficacy. The findings have been published in the internationally renowned journal Radiology.
Complete response rate of current transarterial chemotherapy remains below 30%
According to the latest figures from the Hospital Authority’s Hong Kong Cancer Registry, 1,700 new liver cancer cases were diagnosed in Hong Kong in 2023, 1,400 of them hepatocellular carcinoma (HCC). Nearly half the patients with HCC were at an intermediate or advanced stage when it was first diagnosed, making surgical treatment unfeasible. For patients for whom liver resection is no longer an option, transarterial chemoembolisation is the first-line treatment. Developed decades ago, cTACE produces therapeutic effects by delivering aqueous cisplatin mixed with iodised oil to tumours through a catheter placed at hepatic tumour arteries via an artery in a limb. This procedure was followed by embolisation of blood vessels supplying the tumours, cutting off the tumour’s blood supply and leading to cancer cell death. Currently, three types of transarterial therapies are commonly used to treat HCC. Among them, cTACE has been used for many years, while drug-eluting bead TACE and Yttrium 90 radioembolisation are more recent innovations. However, the rate of complete tumour elimination on imaging from all three treatments remains below 30%.
The Department of Imaging and Interventional Radiology of CU Medicine has developed a novel drug formulation for transarterial chemoembolisation (aTACE), consisting of a suspension of pure anhydrous cisplatin powder mixed with ethiodised oil. Taking advantage of the slow dissolution rate of anhydrous pure cisplatin powder in blood, the drug is not rapidly diluted by blood flow within the tumour. This allows for a high concentration of the drug to be retained and released in a sustained way within the tumour over a prolonged period. This property of aTACE effectively overcomes the drawback of cTACE’s aqueous cisplatin emulsion formulation, in which the drug quickly leaves the tumour through blood flow.
aTACE achieves 90% complete tumour response rate
A multidisciplinary team at CU Medicine conducted a multi-centre, randomised controlled trial between 2016 and 2023 in Hong Kong. It involved 77 participants with intermediate-stage HCC, aged between 49 and 86, who were randomised into aTACE and cTACE groups to compare the efficacy of the treatments. Each participant received two or three treatments every two months, over a period of six months.
Results from the clinical trial showed that the anhydrous cisplatin suspension outperformed the aqueous cisplatin emulsion in all efficacy and survival outcomes. The aTACE group achieved a complete tumour response rate nearly double that of the cTACE group, with a three-year progression-free survival rate three times that of the cTACE group. The median overall survival period in the aTACE group exceeded 53 months, 17.3 months longer than the cTACE group.
Within 30 days after the first treatment, the new formulation had fewer side effects compared to the conventional treatment. Although elevated serum alanine aminotransferase (ALT) levels were more common in the new formulation group, liver function derangement was reversed within two weeks in the majority of participants, with the remainder recovering within 30 days. Serious adverse events such as liver abscess or failure occurred at a lower frequency with aTACE than cTACE.
Comparison of therapeutic efficacy between cTACE and aTACE
| cTACE (38 patients) | aTACE (39 patients) |
|---|---|---|
Complete response rate | 47% | 90% |
Median overall survival period (months) | 36 months | 53.3 months |
Median progression-free survival (months) | 10.4 months | 21.1 months |
Median time to disease progression (months) | 10.7 months | 24.6 months |
Three-year progression-free survival rate | 11.9% | 38.3% |
Adverse event occurrence rate within 30 days of the first treatment |
|
|
| 98% | 82% |
| 87% | 80% |
| 87% | 100% |
Serious adverse event occurrence rate within 30 days | 5.22% | 2.34% |
Dr Lee Kit-fai, Clinical Associate Professor (Honorary) in the Department of Surgery at CU Medicine, said: “These results are encouraging. Currently, the three commonly used transarterial therapies for HCC have similar treatment outcomes, with no significant differences in overall survival. The emergence of aTACE provides a promising treatment option for patients with intermediate-stage HCC.”
Professor Simon Yu Chun-ho, Clinical Professor (Honorary) in the Department of Imaging and Interventional Radiology at CU Medicine, said: “In the past 39 years since the invention of conventional chemoembolisation, medical professionals all over the world have tried their very best to improve the treatment outcomes of transarterial treatment for hepatocellular carcinoma, but there has been no significant breakthrough. After seven years of hard work, the CUHK team is pleased to see that aTACE was shown to be significantly better across all treatment outcome parameters compared with the conventional formulation. This indicates that we have probably developed a better treatment option for patients with intermediate-stage HCC. I would like to sincerely thank all the patients and colleagues who have participated in this study.”
Professor Stephen Chan Lam, Ip’s Family Trust Professor in Clinical Oncology of the Department of Clinical Oncology at CU Medicine, said: “aTACE has not only surpassed the efficacy of existing treatments but also demonstrates CU Medicine’s strength in medical research. The team believes that further larger-scale clinical trials on aTACE will help to promote its wider adoption and benefit more patients.”
Mr. Mak (right), in his seventies, was diagnosed with late stage hepatocellular carcinoma ten years ago. He was subsequently referred to receive four cycles of the novel drug formulation, which successfully reduced the total tumour volume by more than 90%. Nearly ten years after treatment, there has been no sign of recurrence.
The new anhydrous drug formulation, which consists of a suspension of pure anhydrous cisplatin powder mixed with ethiodised oil, delivers therapeutic effects by administering the aqueous cisplatin and iodised oil mixture directly to tumours via a catheter. This is followed by embolisation of the blood vessels supplying the tumours, thereby cutting off the tumour’s blood supply and resulting in cancer cell death.
