Patients with inoperable advanced hepatocellular carcinoma (HCC) may have a chance to live significantly longer by receiving a combined therapy, according to recently reported, mature results from a trial.

The multicenter phase II clinical trial, conducted by the Asia-Pacific Hepatocellular Carcinoma Trials Group and led by the National Cancer Centre Singapore (NCCS) and Singapore General Hospital (SGH), evaluated the efficacy of combining two existing treatment modalities: sorafenib and selective internal radiation therapy (SIRT). The combination therapy involves starting patients on SIRT using SIR-Spheres, a medical device that contains radioactive microspheres labeled with yttrium-90 for short-range, high-energy radiation therapy, followed by systemic therapy with the oral chemotherapy drug sorafenib after 14 days.

Median overall survival was 20.3 months for patients with intermediate-stage HCC and 8.6 months for patients with advanced liver cancer. These final results were better than the preliminary data released in 2010. The mature results were published recently in PLOS ONE (2014; doi:10.1371/journal.pone.0090909).  The trial, which began in 2008, included 29 patients from the countries of Malaysia, Myanmar, Singapore, and South Korea.


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HCC is the most common type of liver cancer with limited treatment options. The disease is diagnosed in approximately 1 million persons annually and only 20% of them are eligible for potentially curative treatment. “This is a major concern and we aim to change that,” said lead investigator Pierce Chow, MBBS, MMed, FRCS, FAMS, PhD, of Singapore General Hospital.

The trial revealed that median time to progression was 15.2 months and 9 months for patients with locally advanced HCC and patients with metastatic liver cancer, respectively. This means that patients are able to enjoy better quality of life for a longer period, from the time therapy starts until the disease progresses.

The results of the trial also compare favorably with the known outcomes of current monotherapy treatments such as the overall survival following transarterial embolization in Asia-Pacific patients with intermediate or advanced HCC (median 18.2 and 6.8 months, respectively).

The trial also demonstrated that patients with locally advanced HCC can also be downstaged to receive potentially curative treatment. In the trial two patients were downstaged to receive radio-frequency ablation. Outside of this phase II trial, four other clinical patients became amendable to surgery after treatment with SIRT and another became amendable to liver transplantation after receiving combination SIRT and sorafenib therapy. Potentially curative treatment such as surgical resection, transplantation, and radiofrequency ablation are otherwise not options for patients with advanced HCC. If left untreated, they have a median survival of about 4 to 8 months.

HCC, a form of liver cancer, is the fifth most common cancer worldwide. Almost 80% of HCC cases are found in the Asia-Pacific region. As the majority of patients with liver cancer do not develop any symptoms, only 1 in 5 patients can potentially be cured by surgery at diagnosis.