European Radiology: Which drugs should patients with HCC choose for TACE treatment?

Hepatocellular carcinoma (HCC) is the most common liver malignancy, accounting for 90%
of the total.
Transcatheter arterial chemoembolization (TACE) significantly improves patient survival compared with conservative management
.
Currently, TACE is the most commonly used treatment modality for unresectable HCC, with doxorubicin being the most widely used
as monotherapy or in combination with other drugs such as mitomycin C or cisplatin.
Unfortunately, the regimens recommended in the TACE guidelines are not supported
by a high level of evidence as only a few clinical studies have compared the use of various chemotherapeutic agents in TACE for HCC.

In the past decade, only two novel platinum-based drugs, LA-12 and bicyclic platin, have been introduced into clinical practice for better clinical tolerability
.
Dicycloplatinum is a supramolecular substance composed of 1,1-cyclobutane dicarboxylate and carboplatin through the four O-H.
.
.
O hydrogen bonds are connected to
each other.
This chemical structure makes it chemically stable, water/fat soluble, and safe, making bicyclic platinum more advantageous
than cisplatin and carboplatin.
Dicyclic platinum can inhibit the proliferation of cancer cells, increase the production of reactive oxygen species and promote apoptosis
.
Since the approval of bicyclic platinum by the State Administration of Pharmaceutical Products in 2012, its anti-cancer effect and drug tolerance have been fully demonstrated
by a series of preclinical in vitro and in vivo studies and clinical trials.

A study published in the journal European Radiology evaluated the effectiveness and safety of bicycline as a chemotherapy regimen for transcatheter arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) and compared
it with other chemotherapy agents in HCC patients who did not respond to TACE or relapsed after cure.

From March 2019 to November 2019, patients with unresectable HCC were enrolled in seven centers in China, each of whom did not respond to TACE or relapsed after surgical resection
or ablation 。 Participants were randomly assigned (1:1:1) to receive a chemotherapy regimen of TACE versus bicycline alone (group A1), bicycline plus epirubicin (group A2), or epirubicin alone (group B).

The primary endpoint was objective response rate (ORR).

Secondary endpoints included disease control rate (DCR), reaction time (DOR), progression-free survival (PFS), and safety
.

The ORR at 6 months was significantly better in group A1 (n = 22) than in group B (p = 0.
093; 90% confidence interval [CI], 1.
03-9.
45).

The DCR in group A1 was significantly higher than in group B (p = 0.
045; 90% CI, 1.
29-12.
88）
。 There was no clear difference in DOR between groups (P = 0.
271).

The median PFS in the A2 group (n = 25) and group B (n = 24) was 6.
00 and 3.
05 months (p = 0.
061),
respectively.
In the safety population, grade 3 or greater adverse events were similar in each group (p = 0.
173).

Figure Kaplan-Meier estimates of progression-free survival in the complete analysis group

This study suggests that TACE with bicycline is comparable
to epirubicin alone in patients with unresectable HCC.
Compared with epirubicin alone, both ORR and DCR were significantly improved
when bicyclic platinum was applied.

Original source:

Hai-Dong Zhu,Xiao Li,Jian-Song Ji,et al.
TACE with dicycloplatin in patients with unresectable hepatocellular carcinoma: a multicenter randomized phase II trial.
DOI:10.
1007/s00330-022-08848-7