Stability of lenalidomide suspension after preparation by a simple suspension method for enteral tube administration.

PURPOSE: A simple suspension method has been developed for tube administration, in which tablets (and capsules) are disintegrated in hot water (55℃) without grinding (or opening) them. In the present study, we evaluated the feasibility of this simple suspension method for the preparation of lenalidomide (Celgene, Summit, New Jersey and USA) suspension by testing the stability of this drug at 55℃ and its adsorbability on the tube. METHODS: We examined, by high-performance liquid chromatography, the time-dependent changes in the concentration of lenalidomide in suspensions of the drug prepared by the simple suspension method. The high-performance liquid chromatography analyses of lenalidomide were performed on Prominence LC-20AB/SPD-20 A (Shimadzu, Kyoto, Japan) with a ZORBAX SB-C18 RR analytical column (Agilent Technologies, Santa Clara, California, USA; particle size: 2.1 × 100 mm, 3.5 µm) at a flow rate of 0.4 mL/min. A solvent system consisting of 10 mM ammonium acetate (pH 7.0)/acetonitrile was used as the eluent and the eluate was detected by UV at 254 nm. RESULTS: Lenalidomide was confirmed to remain stable in hot water at 55℃ for 24 h in the prepared suspension by the simple suspension method, and more than 99% of the drug could be recovered from the suspension. In addition, 94.5-98.0% of the drug amount could pass through a percutaneous endoscopic gastrostomy tube. Lenalidomide was scarcely adsorbed on to the percutaneous endoscopic gastrostomy tube made of polyurethane or polyvinyl chloride. CONCLUSION: Lenalidomide was found to be stable even in hot water and was not adsorbed on to the percutaneous endoscopic gastrostomy tube.

[Evaluation of aprepitant as a prophylactic antiemetic in the Cisplatin split regimen combined with radiation for patients with head and neck cancer].

The cisplatin split regimen has not been sufficiently well investigated to validate the use of aprepitant as a prophylactic antiemetic. This study aimed to retrospectively evaluate the efficacy of repeated administrations of 3-day courses of aprepitant according to the cisplatin split regimen (20mg/m² day, days 1-4, 22-25, 43-46) in combination with radiation. We compared the worst Grade of nausea between 23 patients with head and neck cancer who had been administered with aprepitant (group A: between January 2010 and June 2010) and 34-patients who were not administered with aprepitant (group B: between July 2011 and December 2012). In group A, the median age was 60 years (range, 35-73 years), the male/ female ratio was 18: 5, and the Eastern Cooperative Oncology Group (ECOG) performance status (PS) was 0 in 20 patients and 1 in 3 patients. In group B, the median age was 62 years (range, 31-71 years), the male/female ratio was 30: 4, and the ECOG PS was 0 in 31 patients and 1 in 3 patients. The worst nausea grade was 0, 1, and 2 in 21, 2, and 0 patients in group A and in 19, 9, and 6 patients in group B, respectively. The proportion of patients who developed nausea was significantly lower in group A than in group B (8% vs 44%, p<0.01). Of 6 patients who experienced Grade 2 nausea, 5 patients were administered with aprepitant during the next course of chemotherapy, and 60% of them had a lower severity of nausea. Thus, aprepitant could be effectively used as a prophylactic antiemetic in the cisplatin split regimen.

Moderate renal dysfunction may not require a cisplatin dose reduction: a retrospective study of cancer patients with renal impairment.

OBJECTIVE: The aim of this study was to assess the tolerability of cisplatin (CDDP) in patients with moderate renal dysfunction. METHODS: To investigate the relationship between CDDP dose and nephrotoxicity, a retrospective chart review was conducted of patients with a creatinine clearance (Ccr) of 30-60 mL/min. Subjects were classified into three groups according to the CDDP dose, as determined by the physician, and the nephrotoxicity among these groups was compared. Additionally, we investigated the correlation coefficients between maximum serum creatinine (Scr) level or minimum estimated glomerular filtration rate (eGFR) and baseline Ccr. RESULTS: Fifty-six patients were included in this study. Among these patients, 13 patients received 30-40 mg/m(2) CDDP (group I), 18 patients received 40-70 mg/m(2) (group II), and 25 patients received 70-80 mg/m(2) (group III). No significant difference in nephrotoxicity was observed (median Scr 1.53, 1.61, and 1.53 mg/dL, respectively), and no correlation was observed between baseline Ccr and maximum Scr (r = 0.004, p = 0.979) or minimum eGFR (r = 0.21, p = 0.119). Only two patients (3.5 %) experienced grade 3 or 4 Scr elevation-one patient with a Ccr of 52.6 mL/min received 60 mg/m(2) CDDP, and the other patient with a Ccr of 52.1 mL/min received 70 mg/m(2) of CDDP. Hemodialysis was not observed. CONCLUSION: CDDP was tolerated at doses of 35-80 mg/m(2) among patients with moderate renal impairment. Empiric dose reduction might create a risk of under-treatment.

[Hyperglycemia due to atypical antipsychotics in cancer patients with delirium].

We investigated hyperglycemia due to atypical antipsychotics in cancer patients with delirium. Using patient records retrospectively, we investigated 189 cancer patients who were diagnosed with delirium between June 2008 and May 2009. One- hundred fifty-four of the 189 patients used atypical antipsychotics for delirium treatment. Three percent(5/154)of them were admitted with over 350 mg/dL blood glucose during their atypical antipsychotics treatment, however, all cases did not relate the adverse reaction of hyperglycemia with the use of antipsychotics. Most cancer patients with delirium used atypical antipsychotics, and the incidence of hyperglycemia was low.

Relationship between plasma concentrations of morphine and its metabolites and pain in cancer patients.

OBJECTIVE: This study was undertaken to investigate the relationship between the plasma concentration of morphine, morphine-3-glucuronide and morphine-6-glucuronide and pain in cancer patients receiving oral morphine. METHODS: The trough value of plasma concentrations of morphine and its metabolites were measured by high performance liquid chromatography using an ultraviolet detector. Using this assay system, the plasma concentrations of morphine, morphine-3-glucuronide and morphine-6-glucuronide in 26 cancer pain patients were measured and compared with pain intensity. The pain intensity was assessed at the time of blood sampling using the visual analog scale. RESULTS: The trough value of morphine and morphine-6-glucuronide did not show a significant correlation with pain intensity by visual analog scale assessment, but morphine-3-glucuronide and the ratio of morphine-3-glucuronide/morphine showed a significantly positive correlation (r = 0.528, P = 0.006 and r = 0.671, P < 0.001, respectively). By dividing the group according to low (≤ median value) or high (> median value) VAS scores a significant difference was found between the two groups in morphine-3-glucuronide and the ratio of morphine-3-glucuronide/morphine (P = 0.045 and P = 0.007, respectively). CONCLUSION: These results indicated that the level of morphine-3-glucuronide is related to the patient's perception of morphine effect, and the plasma concentration of morphine-3-glucuronide and the ratio of morphine-3-glucuronide/morphine indicated potency to assess clinical effect.

[Assessment of total bilirubin or SN-38/SN-38G ratio as a predictor of severe irinotecan toxicity].

SN-38, an active metabolite of irinotecan (CPT-11), is glucuronidated into SN-38G mainly by UGT1A1, during detoxification. However, significant interindividual pharmacokinetic variability in SN-38 is caused by factors, including inherited predispositions that may affect the function and expression of UGT1A1. Moreover, these individual differences can contribute to the development of clinical conditions, such as severe leucopenia and diarrhea. Similar to SN-38, bilirubin is excreted into bile after being glucuronidated by UGT1A1. Thus, bilirubin is metabolized by a mechanism similar to that of SN-38. This suggests that the bilirubin level may be an indicator of the adverse effects caused by CPT- 11. On the other hand, the ratio between the AUC of SN-38 and the AUC of SN-38G (AUCSN-38/AUCSN-38G) indicates the ability of SN-38 to be glucuronidated, and is known to correlate with leucopenia and diarrhea. However, many blood sampling points are required to calculate these AUCs. Therefore, the daily estimation of the AUCSN-38/AUCSN-38G values of individual patients is not practical at the clinical level. Thus, the objectives of this study were as follows: (1) to establish whether or not the total bilirubin level is a useful indicator in predicting the development of CPT-11 toxicity. (2) to investigate the correlation of SN-38/SN-38G (the ratio of the serum concentrations of SN-38 and SN-38G) with AUCSN-38/AUCSN-38G. Based on the result of this investigation, it will be discussed whether or not SN-38/SN-38G may be used as an alternative to AUCSN-38/AUCSN-38G. This study included 14 patients with small cell lung cancer or non-small-cell lung cancer, in whom serum concentrations of CPT-11, SN-38, and SN-38G were measured by HPLC. The results demonstrated a significant correlation between the total bilirubin levels prior to chemotherapy and the logarithmic values for AUCSN-38/AUCSN-38G (r2=0.852). Among the cases with high values for both the total bilirubin level and the AUCSN-38/AUCSN-38G ratio, none of the patients had grade-3 diarrhea, while many cases tended to have grade-3 to -4 neutropenia. Additionally, the results of regression analysis suggest that SN-38/SN-38G (2 hr) and SN-38/SN-38G (4 hr) might be preferable as a predictive index for AUCSN-38/AUCSN-38G. These findings suggest that the total bilirubin level and SN-38/SN-38G, 2 to 4 hours after administration might be used as indicators to predict CPT-11-induced neutropenia. These indicators are likely to contribute to the pharmacogenetic analysis of UGT1A1 genes, as well as individualized therapy, in future, and further studies on this subject are expected.

Evaluation of the impact of a flowchart-type leaflet for cancer inpatients.

OBJECTIVES: This study aimed to evaluate the benefits of an interactive and visual flowchart-type leaflet for head and neck cancer inpatients who received induction chemotherapy, docetaxel, cisplatin, and 5-fluorourasil (DCF), or docetaxel, cisplatin, and S-1 (DCS) from September 2009 to April 2012. The flowchart-type leaflet group used a flowchart-type leaflet during chemotherapy, while the non-flowchart-type leaflet group did not. METHODS: A retrospective cohort study was performed using patient records. The endpoints of this study were to determine the following: the number of emergency hospital admissions/visits, incidence of Grade 2 or higher non-haematological adverse drug reactions, nonadherence to treatment, and the number of telephone calls from subjects. RESULTS: A total of 109 subjects were identified as follows: 49 in the flowchart-type leaflet group (139 chemotherapy sessions) and 60 in the non-flowchart-type leaflet group (163 chemotherapy sessions). No significant differences were observed in age, performance status, or chemotherapy regimen. The incidence of emergency hospital admissions was significantly lower in the flowchart-type leaflet than in the non-flowchart-type leaflet group (1% vs 10%, p < 0.01). No difference was seen between groups (12% vs 19%, p = 0.1) in the nonadherence rate of supportive medication for adverse drug reactions. Telephone call rates were significantly higher in the flowchart-type leaflet (16%, 30 calls) than in the non-flowchart-type leaflet group (7%, 11 calls) in each chemotherapy regimen. Of the 30 calls from patients in the FCL group, 24 (80%) were made to the hospital, compared with only 5 (45%) of the 11 calls from patients in the non-flowchart-type leaflet group. CONCLUSIONS: Our results suggest that the flowchart-type leaflet can reduce nonadherence and improve patient judgment during chemotherapy, leading to a decrease in emergency hospital admissions.