Clinical trials for liver and pancreatic cancer in Taiwan

Although with limited clinical activity, gemcitabine monotherapy is still the standard of care for patients with advanced pancreatic cancer. To improve the therapeutic results of gemcitabine for advanced pancreatic cancer, we firstly had a phase I/II study to determine the maximum tolerated dose of 24-hour infusion of high-dose 5-FU and leucovorin (HDFL) in combination with weekly 800 mg/m2 of gemcitabine in advanced pancreatic cancer. With the recommended dose of 5-FU, which was determined to be 2000 mg/m2, the gemcitabine-HDFL regimen could achieve 22% of response rate, 6.9 months of overall survival and acceptable toxicity profile in advanced pancreatic cancer. Then we further incorporated oxaliplatin into the gemcitabine-HDFL regimen. The three drug combination – gemcitabine, oxaliplatin plus infusional 5-FU and leucovorin (GOFL regimen) has been shown to be feasible and moderate active in patients with advanced pancreatic cancer, not only as the primary therapy for patients with advanced diseases but also as an inductional chemotherapy for patients with unresectable, locally advanced diseases. Further randomization will be warranted to evaluate the true clinical benefit of the triplet regimen in patients with advanced pancreatic cancer.
In recently years, molecular targeting agent either alone or in combination with chemotherapy or other targeting agents is the mainstream for hepatocellular carcinoma (HCC) studies in Taiwan, as well as the rest part of the world. However, the targeting therapy for advanced HCC in Taiwan was started with the thalidomide program in 1999. We firstly completed a phase I and pharmacokinetic study to show that severity of underlying cirrhosis does not affect the absorption and elimination of thalidomide in HCC patients, and the maximum tolerated dose and recommended dose of thalidomide for HCC patients was 300 and 200 mg/day, respectively. Further studies suggested that oral thalidomide has a potential to stabilizing the progression of advanced HCC (30-40% of disease stabilization rate with objective response in 5-10%) even in patients with severe underlying cirrhosis. Based on such observations, a placebo-controlled phase III trial has been taken to evaluate the true therapeutic effects of thalidomide in Child-Pugh’s B/C HCC patients. In addition, to improve the surgical outcome of patients with curative resection of HCC, we had also conducted a randomized, phase III TCOG trial to evaluate whether the use of interferon-α, an anti-virus, anti-proliferative, and anti-angiogenic immunomodulator, could reduce or delay the recurrence and thus, to improve the survival in post-operative HCC patients or not. This is the largest adjuvant therapy trial for (target patients population: 268) post-operative HCC in the world. The preliminary results will be disclosed in the text.