Induction: All patients receive oral sorafenib twice daily on days 1-28. Treatment continues for 2 cycles in the absence of disease progression or unacceptable toxicity. Patients with stable disease proceed to randomization.

Randomization: Patients with stable disease after the induction treatment were randomized to receive either sorafenib or placebo. Patients on the sorafenib arm receive sorafenib twice daily for up to 1 year in the absence of disease progression or unacceptable disease.

In the study design, only patients on the placebo arm with progressive disease may cross over to receive sorafenib. Due to drug dispensing error, even though some patients actually received straight sorafenib during Step 2 (randomization) treatment, they were thought to be randomized onto the placebo arm upon progression and unblinding (before finding out the fact of the dispensing error). Consequently, these patients were crossed over to Step 3, and there were 10 of them.

Induction: All patients receive oral sorafenib twice daily on days 1-28. Treatment continues for 2 cycles in the absence of disease progression or unacceptable toxicity. Patients with stable disease proceed to randomization. Patients with responding disease continue to receive sorafenib for up to 1 year in the absence of disease progression.

Randomization: Patients with stable disease after the induction treatment were randomized to either the sorafenib arm or the placebo arm. Patients on the sorafenib arm receive sorafenib twice daily for up to 1 year in the absence of disease progression or unacceptable disease. Patients on the placebo arm receive oral placebo twice daily for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients on the placebo arm who develop disease progression within 1 year after randomization may cross over to sorafenib arm.

Induction: All patients receive oral sorafenib twice daily on days 1-28. Treatment continues for 2 cycles in the absence of disease progression or unacceptable toxicity.

Patients with responding disease continue to receive sorafenib for up to 1 year in the absence of disease progression.

Randomization: Patients with stable disease after the induction treatment were randomized to either the sorafenib arm or the placebo arm.

To show baseline characteristics for eligible and treated patients in both the randomization phase (the most important part of this study) and the induction phase, this group contains the following patients:

• eligible and treated patients who were not randomized (n=194)
• randomized patients who were not eligible or did not start treatment in the randomization phase (n=24)

There were 218 patients in this group so the total number of patients is 299 and the entire cohort represents all eligible and treated patients in the induction phase.

Total of all reporting groups

All patients who received induction treatment (333 patients), regardless of eligibility status, were included in the toxicity analysis.

After induction treatment, 59 patients were randomized to the sorafenib arm. Among these, 55 received treatment. However, due to drug dispensing error, 10 of them received mixed treatment with sorafenib and placebo and were categorized into "Randomization (Step 2): Mixed" group when reporting toxicities. As a result, 45 treated patients were included in the "randomization (step 2): sorafenib" group.

After induction treatment, 46 patients were randomized to the placebo arm. Among these, 40 received treatment. However, due to drug dispensing error, 2 of them received mixed treatment with sorafenib and placebo and were categorized into "Randomization (Step 2): Mixed" group when reporting toxicities. As a result, 38 treated patients were included in the "randomization (step 2): placebo" group.

After induction treatment, patients with stable disease were randomized to receive either sorafenib or placebo. Due to drug dispensing error, 10 patients from the sorafenib arm and 2 patients from the placebo arm (12 pts in total) received mixed treatment with sorafenib and placebo and were categorized into "Randomization (Step 2): Mixed" group when reporting toxicities.

Patients on the placebo arm who develop progressive disease may cross over to receive sorafenib, and 27 patients from the placebo arm received sorafenib in Step 3 (crossover). Due to drug dispensing error, even though some patients actually received straight sorafenib during Step 2 (randomization) treatment, they were thought to be randomized onto the placebo arm upon progression and unblinding (before finding out the fact of the dispensing error). Consequently, these patients were crossed over to Step 3, and there were 10 of them. In total, 37 patients registered to step 3 (crossover). Of these, 35 patients received treatment and were included in the toxicity analysis for the crossover (step 3) part.