Nakata et al. Journal of Experimental & Clinical Cancer Research 2010, 29:15 http://www.jeccr.com/content/29/1/15 Page 3 of 7 Figure 1 Drug administration and blood sampling schedule. calculated according to the trapezoidal rule using the WinNonlin program (Ver. 5.2; Pharsight Co., Mountain View, CA, USA). Two-sided paired Student’s t-test on log-transformed plasma concentration data was used to compare the maximum concentration (Cmax) and AUCinf between single administration and co-adminis- tration. The two-sided paired Student’s t-test was con- ducted on the elimination half-life (T 1/2) and time required to reach Cmax (T max) in order to compare data for single administration and co-administration. A P value of < 0.05 was considered to be statistically significant. Results Clinical outcome Five of six patients were treated by GEM+S-1 for 5 to 16 courses (median, 8 courses). However, it was neces- sary to reduce the doses of S-1 and/or GEM by approxi- mately 25% due to grade 3 or more neutropenia for two patients after one course, and for two patients after three courses. The regimen was stopped at the end of one course in one patient who could not continue oral intake of S-1 due to developing the stenosis at Treitz ligament by cancer invasion. The MST of total patients studied was 12.5 months, ranging from 3 to 22 months. The 1-year survival rates were 67%. One partial response was observed. SPan-1, one of reliable tumor marker for pancreatic cancer [9], titers in sera were decreased 50% or more in all of 5 patients who had abnormal level of SPan-1 prior to the treatment. Plasma PK There were no significant differences between plasma PK parameters of GEM after administration of GEM alone and GEM+S-1 (Table 1, Figure 2). There were no significant differences between the plasma PK para- meters of 5-FU after administration of S-1 alone and GEM+S-1 (Table 2, Figure 3). Discussion For the last decade, GEM monotherapy has been the standard chemotherapy regimen to treat advanced pan- creatic cancer. The drug has an approximately 5% response rate and improves MST to less than 6 months [10]. Clinical trial data has demonstrated a response rate of 44-48% and an MST of 10.1-12.5 months when S-1 is administrated with GEM [6,7]. The efficacy of this com- bination therapy, including our regimen, thus appears to