Comparison between filgrastim biosimilar and filgrastim original for the management of neutropenia after salvage chemotherapy for malignant lymphoma.

In this study, the efficacy and safety of filgrastim biosimilar (F-BS) were retrospectively compared to those of filgrastim original in the treatment of malignant lymphoma with CHASE (± R) or DeVIC(± R) in 78 patients. The median number of filgrastim doses was 11 in the F-BS group and 8 in the filgrastim group after CHASE (± R) (p = 0.8), and 10 in the F-BS group and 10 in the filgrastim group after DeVIC (± R) (p = 0.45). The median days until neutrophil recovery to ≥ 1000/µL was 10 days with F-BS versus 10 days with filgrastim after CHASE ± R (p = 0.59), and 9 days with F-BS versus 10 days with filgrastim after DeVIC ± R (p = 0.828). Febrile neutropenia (FN) was observed in 5 patients (41.7%) in the F-BS group and 9 (52.9%) in the filgrastim group after CHASE ± R therapy (p = 0.616), and in 11 patients (36.7%) in the F-BS group and 9 (47.4%) in the filgrastim group after DeVIC ± R (p = 0.462). The present results suggest that the efficacy and safety of F-BS are comparable to those of filgrastim original, with no significant differences in clinical factors. Use of F-BS also reduced medical costs per course of CHASE ± R therapy by 170.22 US dollars.

A prospective feasibility study of primary prophylaxis against invasive fungal disease with voriconazole following umbilical cord blood transplantation with fludarabine-based conditioning.

Despite the recent introduction of a new class of anti-Aspergillus agents, no standard regimen for the prevention of invasive fungal disease (IFD) following allogeneic hematopoietic stem cell transplantation has been shown to be superior to fluconazole. The present prospective, single-arm study investigated the feasibility of voriconazole (VOR) administration as primary prophylaxis in 52 recipients of umbilical cord blood transplantation (CBT) with fludarabine-based conditioning, who had no previous IFD episodes. Proven or probable IFD was determined using the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group, and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) criteria were considered as breakthrough infections. VOR was administered as prophylaxis for a total of 6884 patient-days following CBT. The mean duration of VOR administration after transplantation was 132 days (range, 1-769); 44 patients (85 %) had advanced disease, 15 (29 %) had a history of allogeneic HSCT, and 29 (56 %) received systemic corticosteroid therapy for allogeneic immune-mediated complications. Under the prophylaxis with VOR, one patient developed probable invasive aspergillosis on day 71, and the cumulative incidence of IFD was 4.5 % at day 180. None of the patients developed breakthrough candida or zygomycetes infections. Under the extensive therapeutic dose monitoring, VOR was safely administered with a calcineurin inhibitor and was well tolerated. These results suggest that VOR represents a feasible primary prophylactic agent for IFD after CBT with fludarabine-based conditioning.

[Magnesium premedication prevents Cisplatin-induced nephrotoxicity in patients with esophageal and hypopharyngeal cancer].

Hypomagnesemia is one of the well-known side effects in patients receiving cisplatin-containing chemotherapy. However, the relevance between hypomagnesemia and cisplatin-induced nephrotoxicity remain to be completely elucidated. Although patients with esophageal and hypopharyngeal cancer are susceptible to dehydration, there is no evidence yet that magnesium supplementation for these patients will prevent nephrotoxicity during cisplatin-containing chemotherapy. The aim of this study was to examine the effect of magnesium supplementation on the prevention of cisplatin-induced nephrotoxicity for patients with esophageal and hypopharyngeal cancer. Twenty-three patients with esophageal or hypopharyngeal cancer were studied over 2 weeks. Ten of them received magnesium supplementation and 13 did not. Magnesium sulphate(20 mEq) was administered before 5-fluorouracil(800mg/m2/24 h/day 1-5)and cisplatin(80mg/m2/day 1)(FP)treatment. The maximum serum creatinine concentration of magnesium-supplemented group demonstrated a significantly lower concentration compared to the non-magnesium-supplemented group(p=0. 018). As a result, magnesium supplementation successfully reduced the incidence rate of nephrotoxicity(p=0. 038). These results showed that magnesium supplementation before FP treatment may be quite beneficial for preventing nephrotoxicity in patients with esophageal and hypopharyngeal cancer, and it is therefore recommended that magnesium be routinely supplemented during FP treatment for esophageal or hypopharyngeal cancer.

[A case report of severe hypo-phosphatemia due to paraneoplastic syndrome followed by severe hyper-phosphatemia due to tumor lysis syndrome after CHOP chemotherapy].

A 51-year-old man who underwent umbilical cord blood transplantation for acute lymphoblastic leukemia with a Philadelphia chromosome in April 2006 achieved complete remission. In June 2008, progressive renal dysfunction and melena emerged and the patient was diagnosed with B-cell-type malignant lymphoma. He presented with severe hypo-phosphate- mia(0. 1m g/dL)due to paraneoplastic syndrome, simultaneously. Because the development of tumor lysis syndrome followed by hyper-phophatemia was feared to occur after CHOP chemotherapy, we discontinued the adjustment of serum phosphorus. The serum phosphorus level was elevated to 11.6mg/dL after 3 days and decreased to 3. 8mg/dL after 5 days. We must be careful regarding hyper-phosphatemia and phosphorus adjustment even in patients with severe hypo-phosphatemia that is due to paraneoplastic syndrome.

[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.

[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.

[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.

[Modified FOLFOX6 in a patient on hemodialysis with metastatic colorectal cancer].

Since pharmacokinetics in patients undergoing hemodialysis differs from that in patients with normal renal function, chemotherapy for a hemodialysis patient should be considered with due care. We administered chemotherapy of modified FOLFOX6 to a patient on hemodialysis with inoperable metastatic colorectal cancer, and measured his plasma concentration of total platinum and non-protein-bound platinum. Since there is no reported case of oxaliplatin use in patients on hemodialysis so far, we evaluated whether it could be safely used for such patients. We made a dose escalation study with 40, 50, 60, 70 and 85 mg of oxaliplatin, and evaluated the pharmacokinetics at each dose. AUC was 5.67-10.21 mg/L x h. The dialysis removal rate was 84.0%. Although this patient could accept it relatively safely without any severe side effect, the optimal dosage and the timing of hemodialysis for inoperable metastatic colorectal cancer patients should be determined by a further study using more cases.

[Therapeutic drug monitoring].

Practicing pharmaceutical care is necessary to promote the appropriate use of medicines. In the practice of pharmaceutical care, monitoring the efficacy and safety of drugs from the pharmacists' point of view is an important role for clinical pharmacists and it is necessary to standardize clinical skills. We would like to introduce the monitoring skills of pharmacotherapy of clinical pharmacists by taking vancomycin injection and injectable anticancer drugs that have different monitoring points as examples.