[Optimal therapeutic concentration of tacrolimus in adult patients undergoing reduced-intensity cord blood transplantation].

To investigate the effectiveness and safety of GVHD prophylaxis using FK506 alone as a continuous infusion, 104 patients who underwent reduced-intensity cord blood transplantation were retrospectively reviewed. The respective incidence of acute GVHD was 25 grade 1(24. 1%), 19 grade2(18. 3%), 15 grade3(14. 4%), and 4 grade4(3. 8%), which are comparable to that in the literature. The incidences of grade 2 and greater acute GVHD were 32 out of 69(46. 4%)for those whose wholeblood concentration of FK506 werele ss than 13 ng/mL, whereas 6 out of 35(17. 1%)for those FK5 06 were greater than 13 ng/mL. The differenceies between above and below 13 ng/mL were statistically significant(p=0. 008). There were 19 cases(18. 3%)of renal dysfunction, although none required hemodialysis. There were only 4 patients who discontinued FK506, which further confirmed the safety of FK506 alone. Together with our previous report on the upper limit of FK506(17 ng/mL)and these results, we recommend the optimal serum concentration of FK506 to range from 13 to 17 ng/ mL.

[Evaluation of efficacy and safety of first-line docetaxel/cisplatin/5-FU combined therapy for advanced esophageal cancer].

We retrospectively evaluated the efficacy and safety of a first-line combination chemotherapy with Docetaxel, Cisplatin, and 5-fluorouracil (DCF therapy) in nine patients with advanced esophageal cancer. Dose administrated were 75 mg/m² of Docetaxel on day 1, 75 mg/m² of CDDP on day 1, and 750 mg/m² of 5-FU on day 1-5. Complete response (CR) in two patients (22. 2%), partial response (PR)in three patients ( 33. 3%), and no change (NC) in four patients (55. 6%) were shown for main lesions, while CR in one (11. 1%), PR in five (55. 6%), and NC in three (33. 3%) were shown for lymph node metastases. Response rates of the DCF therapy were 55. 6% for main lesions and 66. 7% for lymph node metastases. Five patients who achieved PR or CR underwent esophagectomy with lymph node dissection. Toxicity from DCF therapy was grade 3 or 4 emergent adverse events (77. 8% of neutropenia, 55. 6% of febrile neutropenia, and 55. 6% of anorexia). DCF therapy improved the response rate in esophageal cancer patients, but resulted in some increase in toxicity. Prospective study with prevention of toxicity should be planned in order to evaluate first-line DCF therapy for advanced esophageal cancer.

[Analysis of blood concentrations following oral administration of beclomethasone dipropionate for gut GVHD].

In this study, we investigated the level of gut absorption following oral beclomethasone dipropionate (BDP) administration by measuring the blood concentration of its metabolites measured by LC-MS/MS using the HPLC method. Five patients who were administered BDP orally for gut GVHD were included. The blood concentrations of beclomethasone-17-monopropionate (17BMP), which is one of the active metabolites of BDP, were 618 approximately 1, 749 pg/mL in 4 of the studied 5 patients, which was comparable to that after inhalation of BDP; however, it was relatively higher in one patient (2,439+/-161 pg/mL). As the blood concentration of 17BMP in this study patient was higher compared with healthy volunteers administered a single oral BDP 4 mg, GVHD patients might have a higher concentration than healthy volunteers. Given that a higher grade of gut GVHD was associated with a higher blood level of 17BMP, BDP absorption might be associated with gut mucosal injury. Thus, the systemic adverse effect following oral BDP administration might not be negligible especially in gut GVHD patients.