The mature results from a trial conducted by the Asia-Pacific Hepatocellular Carcinoma Trials Group led by the National Cancer Centre Singapore (NCCS) and Singapore General Hospital (SGH) have shown that patients who suffer from inoperable advanced hepatocellular carcinoma (HCC) may have a chance to live significantly longer by using a combined therapy.
The multi-centre phase II clinical trial was conducted at four Asia Pacific tertiary medical centres to evaluate 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 microspheres, a medical device that contains radioactive microspheres labeled with yttrium-90 for short range high energy radiation therapy, followed by systemic therapy with an oral chemotherapy drug, Sorafenib, 14 days later.
The mature results of the trial published recently in a peer-reviewed journal, PLOS ONE, show that 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.
Led by Prof Pierce Chow, Senior Consultant Surgeon at NCCS and SGH, the investigator-initiated trial, which commenced in June 2008, recruited 29 patients from four countries namely Malaysia, Myanmar, Singapore and South Korea.
"Hepatocellular carcinoma is the most common type of liver cancer with limited treatment options. About 1 million individuals are diagnosed with the condition annually and only 20 per cent of them are eligible for potentially curative treatment. This is a major concern and we aim to change that," said Prof Chow.
"It is through collaboration with hospitals and medical centres in the region that we can further our understanding of this disease that is so prevalent in the Asian population. This multi-centre phase II clinical trial, which showed that the combination therapy improves survival, is an example of how patients can benefit from the collaboration."
The trial also 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 till 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).
"This is an improvement of the initial result in 2010, which were already better than treatment with either therapy alone. It is very encouraging as it justifies our perseverance in seeking a deeper understanding of how we can treat this form of cancer to achieve the best results for our patient, " said Prof Soo Khee Chee, Director of NCCS who is also involved in the Phase II study.
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 5th most common cancer worldwide. Almost 80 per cent of HCC cases are found in the Asia-Pacific region. As the majority of patients with liver cancer do not develop any symptoms, only one in five of them can potentially be cured by surgery when diagnosed.
In view of the success of the phase II trial, the phase III multi-centre trial has commenced to determine if SIRT would help patients survive longer and would potentially be the first line therapy for advanced HCC.