Although testicular cancers are highly curable malignancies, conventional cisplatin based therapy often causes important toxicities, not often easily manageable. Nephrotoxicity occurs in almost all patients, and is potentialized in patients suffering from renal failure. Monitoring of residual levels of unbound platinum was used to define guidelines for cisplatin administration.

Monitoring of cisplatin was initiated in a patient treated for metastatic testicular cancer and acute renal failure. Reduced doses of cisplatin were first administered in conjunction with hemodialysis. Unbound and total platinum levels were determined by flameless atomic absorption spectrophotometry.

The data found allowed us to adapt and increase sequentially cisplatin doses, accordingly with the renal function. Full regimen doses were eventually administered when useful renal function returned.

This simple approach may be useful in monitoring cisplatin administration during acute renal failure.

Purpose. To review current knowledge about tumor lysis syndrome (TLS), a set of metabolic imbalances, including hyperuricemia, that often occur during chemotherapeutic or biotherapeutic treatment of patients with hematologic malignancies.

Data sources. English language journal articles indexed in PubMed.

Study selection. Recent reviews and original research articles related to TLS, hyperuricemia, and treatment of hyperuricemia were selected for inclusion.

Results. The incidence of TLS depends highly on the type of malignancy, its growth characteristics, and the total tumor burden. Patients are at heightened risk if they have hyperuricemia, hypovolemia, or poor renal function before anticancer therapy begins. Recently published guidelines make risk assessment and patient staging more systematic. Prophylactic measures should be used to reduce the risk for TLS in vulnerable patients. Such measures include hydration to facilitate urinary excretion and administration of allopurinol to prevent de novo production of uric acid. If hyperuricemia occurs despite preventative efforts, uric acid concentrations can be reduced with rasburicase, a recombinant, intravenously administered urate oxidase. The cost of rasburicase therapy is substantial but is considerably less than that of hemodialysis and extended hospitalization. Shorter courses or smaller doses of rasburicase than those recommended may be effective in reducing hyperuricemia in some patients, but it is important to recognize that the alternative dosing still awaits validation.

Conclusions. Allopurinol and rasburicase are recommended for preventing hyperuricemia in patients at intermediate or high risk for TLS, respectively. If hyperuricemia develops despite preventative measures, rasburicase treatment is an effective method for lowering uric acid concentrations within normal limits.

Purpose. The pharmacology, pharmacokinetics, pharmacodynamics, clinical utility, adverse effects, dosage, and cost of lenalidomide are reviewed.

Summary. Lenalidomide is a thalidomide analogue approved for treatment of myelodysplastic syndromes (MDS) associated with a cytogenetic 5q deletion. In combination with dexamethasone, lenalidomide has been approved by the FDA in the United States for the treatment of relapsed or refractory multiple myeloma, and is sometimes used for induction therapy. Although the precise mechanism of action of lenalidomide remains unknown, it does exhibit antineoplastic and immunomodulatory properties. Lenalidomide is quickly absorbed after oral administration and is renally eliminated. In patients with myelodysplatic syndromes, lenalidomide reduces the need for transfusion. In patients with refractory or relapsed multiple myeloma, lenalidomide in combination with dexamethasone demonstrated a significantly longer time to tumor progression compared to placebo plus dexamethasone. Lenalidomide in combination with dexamethasone also elicited an objective response from patients with newly diagnosed symptomatic multiple myeloma. Treatment with lenalidomide was associated with neutropenia, thrombocytopenia, constipation, pruritus, and fatigue. Due to the teratogenic nature of thalidomide, lenalidomide must be obtained through a restrictive distribution program. The initial daily dosing of lenalidomide is 10 mg for MDS with a 5q deletion and 25 mg for relapsed or refractory multiple myeloma. Dose modifications are required for renal impairment and grade 3–4 adverse events.

Conclusion. Lenalidomide is an effective agent for the treatment of MDS with a 5q deletion and relapsed or refractory multiple myeloma.

Purpose. Oral mucositis is a serious problem that affects a significant number of hematopoietic cell transplant (HCT) patients. There are many gaps in management, and evidence-based guidelines do not provide consistent recommendations. The purpose of this pilot study was to develop a mucositis oral care protocol for the prevention and management of mucositis in the HCT patient and to evaluate the clinical impact of its implementation.

Methods. After receipt of Institutional Review Board approval, all patients admitted to the Hematology–Oncology service for high-dose chemotherapy followed by an autologous or allogeneic HCT were eligible for the study. As part of a change in practice, a new mucositis protocol consisting of a specific oral care regimen was instituted for prevention and treatment of mucositis. Assessment of mucositis began upon admission to the hospital and the patient was evaluated using a mucositis grading scale on a daily basis by the physician and nursing staff. The new mucositis protocol was a part of the HCT service admission orders for each patient. The group of patients treated according to the new mucositis protocol were compared with a retrospective control group consisting of patients who had undergone management of oral mucositis under the previous standard of care. The primary endpoints were to evaluate incidence, severity, and duration of oral mucositis. Secondary endpoints included days requiring narcotics; days of parenteral nutrition, febrile neutropenia, antimicrobial therapy, and length of hospital stay.

Results. There were 13 patients enrolled in the control group and 12 patients in the new protocol group. The new protocol resulted in a decreased incidence (100% vs. 75%) and duration (19.2 vs. 8.3 days) of mucositis. Days of maximum grade one and three mucositis were decreased by 56%, and 70%, respectively. Days of maximum grade two mucositis, however increased by 22%. The days of narcotic use were reduced by 19% in the new protocol group (15.8 vs. 12.8 days). All patients in the new protocol group required parenteral nutrition, but days of use were reduced by 41% (17 vs. 10.2 days). The incidence of infection measured by days of febrile neutropenia and antimicrobial therapy were reduced by 35% (10.2 vs. 6.5 days) and 33% (17 vs. 11.4 days). Finally, the overall length of hospital stay was reduced by 7 days (30 vs. 23 days).

Conclusion. Implementation of a standardized oral care protocol for mucositis management resulted in a decreased incidence, duration and severity of mucositis, and also reduced the global negative impact of mucositis. Future studies may further evaluate the global impact by adjusting for confounding factors.

Introduction. One of the main reasons for the implementation of computer-based prescribing was to reduce medication errors. However, the risk has not fallen to zero and new kinds of errors have been detected.

Setting. The following case relates one of these medication errors involving a preparation of vincristine. This antineoplastic drug was injected to a patient via a subcutaneous route of administration instead of an intravenous bolus injection.

Results. Consequently, a cutaneous erythema appeared. This incident resulted from an error in the programming of the administration route of the protocol operated by a pharmacist and a physician. The pharmacist, who was responsible for the validation of the computerized medical order and then for the compounding and the dispensing of the drug, did not detect the error.

Conclusion. This case highlights the need of improved and irreproachable therapeutic protocols. Recorded in a database, they must be validated pharmaceutically and medicinally to secure computer-based prescribing, drug handling, dispensing, and administering of the antineoplastic drugs. Even if the pharmaceutical analysis of prescriptions is made easier with computerization, we encourage the training of nurses and the evaluation of their knowledge as well as the necessity for pharmacists to learn to detect new kinds of errors and to verify periodically protocols.

Introduction. Capecitabine is an oral fluoropyrimidine that was designed to allow selective activation in tumour tissues, thus reducing toxicity. The neurologic toxicity of 5-fluorouracil, the original fluoropyrimidine, including an ataxic cerebellar syndrome is well described. However, only a few case reports exist describing a similar syndrome associated with capecitabine administration.

Case Report. We report a case of reversible cerebellar toxicity during chemotherapy with a combination of capecitabine and oxaliplatin.

Discussion. Rare fluoropyrimide-related toxicities are increasingly being reported in association with capecitabine. Clinical vigilance is required to ensure appropriate investigation and treatment.

Purpose. To describe the successful use of glucarpidase (carboxypeptidase G2) in the treatment of high-dose methotrexate-induced nephrotoxicity in a patient with osteosarcoma.

Summary. A 12-year-old female patient who had been diagnosed with low-grade right mandibular osteosarcoma was started on a protocol of cisplatin plus doxorubicin alternating with high-dose methotrexate. Following her first dose of methotrexte, she developed acute renal failure and higher than expected 24 h methotrexate level of 478 µM/L. High-dose leucovorin rescue was started with vigorous hydration and urine alkalinization together with two sessions of hemodialysis. Because her methotrexate level was persistently high, the investigational drug glucarpidase was administered. Methotrexate level dropped from 65 to 16.3 µM/L after a single dose of glucarpidase measured by fluorescence polarization immunoassay. Leucovorin and urine alkalinization were continued until day 17 when the patient’s kidney function normalized and methotrexate level reached 0.05 µM/L. The patient tolerated glucarpidase well without any significant adverse events.

Conclusion. Glucarpidase is a safe and effective agent in the management of high-dose methotrexate-induced nephrotoxicity and delayed methotrexate elimination.

Background. Platinum, antracyline, and fluoropyrimidine combination chemotherapy has been widely used as a first-line treatment for advanced gastric cancer (AGC). In the present study, we determined the efficacy and the safety of docetaxel and oral etoposide as second-line combination chemotherapy after failure of commonly used combination regimens in AGC.

Methods. Patients with histologically proven gastric cancer and measurable metastatic disease received docetaxel 75 mg/m² as a 1-h intravenous infusion on day 1, and oral etoposide 50 mg/m² once daily on days 1–5, every 3 weeks until disease progression or unacceptable toxicities.

Results. Between June 2006 and September 2008, 32 patients, of median age 60 years (range 32–77 years) were included in the study. Overall response rate was 9.4% and 31.3% of patients achieved a stable disease. Median progression-free survival was 3 months (95% CI, 2.5–3.5). Median overall survival was 6 months (95% CI, 3.8–8.2) with 16.9% 1-year survival rate. Grade 3–4 toxicities included neutropenia (28.8%), febrile neutropenia (18.8%), thrombocytopenia (3.1%), nausea and vomiting (15.6%), diarrhea (9.4%), and mucositis (6.2%).

Conclusion. Docetaxel and oral etoposide combination was moderately effective and safe in appropriately selected AGC patients after failure of platinum- and fluoropyrimidine-based combination regimens.

Purpose. Standardizing body surface area (BSA) determination is essential for avoiding variation in chemotherapy dosage calculations. In this study, we compared variation in BSA calculation using weight and height by the Mosteller formula with weight alone using recently adapted table at a local oncology center.

Methods. Cross-sectional study of pediatric oncology patients presenting to a pediatric oncology clinic over a week period of time.

Results. One-hundred consecutive pediatric oncology patients presented to the clinic. The mean BSA calculated by the Mosteller formula was 0.83 m² (SD 0.24) and the mean BSA determined by the table (based on weight alone) was 0.82 m² (SD 0.25). The mean variation in dosing between the two methods was 1.64% (SD 3.4). Only 13 out of 100 patients (13%) had equal dosing using both methods and 21 out of 100 patients (21%) had dosing variation greater than 5%. When comparing both methods, using paired t-test, the difference was statistically significant (t₍₉₉₎ = 3.99 and p < 0.001).

Conclusion. Significant differences in BSA-based chemotherapy dosing exist in our center. The Mosteller method should remain the standard until prospective studies are performed to determine the significance of this dosing variability on toxicity and survival outcome.

Objectives. Preparation of intravenous solution in advance could be efficient to improve quality assurance, security, time management, and cost saving of drug delivery. The purpose of this study was to investigate the stability of a mixture of tramadol chlorhydrate and metoclopramide hydrochloride in dextrose 5% polyolefin bags at 4°C.

Methods. The stability of five bags of solution containing 100 mg tramadol and 10 mg metoclopramide per 100 mL dextrose 5% and stored at 4°C was studied during 32 days and concentrations measured by high performance liquid chromatography-diode array detection.

Results. No degradation interference nor modification in retention times were observed throughout the study period. At day 32, tramadol concentration was 96.9% ± 2.1 and metoclopramide 97.2% ± 1.3 of the initial concentration.

Conclusion. Based on a shelf-life of 90% residual potency, tramadol and metoclopramide were compatible and stable for at least 32 days at 4°C and can be prepared in advance in a centralized intravenous additive service facility.

Objective. To determine whether forced diuresis and sodium loading or sodium loading alone is better at preventing cisplatin-induced nephrotoxicity.

Methods. Records of 92 patients receiving cisplatin >40 mg/m² and sodium loading with or without mannitol were reviewed to determine the incidence of nephrotoxicity, average decline in creatinine clearance, degree of nephrotoxicity, time to resolution, rates of hospitalization, and electrolyte abnormalities among patients receiving sodium loading or sodium loading with forced diuresis.

Results. The mean cisplatin dose was 64.5 mg/m² with a majority of the subjects receiving treatment for lung cancer. The patients who received sodium loading experienced an average decline in creatinine clearance of 33.9 mL/min versus a decline of 38.9 mL/min in the group receiving forced diuresis and sodium loading (p = 0.09). Incidence of nephrotoxicity, rate of hospitalization and rates of hypokalemia or hypomagnesemia were similar between the groups. Time to resolution of nephrotoxicity was significantly different between the groups, although there were limitations in evaluating this outcome. Majority of the subjects in the sodium loading group experienced NCIC-TC Grade 0 nephrotoxicity, whereas half of the patients in the forced diuresis group experienced Grade 2 nephrotoxicity.

Conclusion. We detected no difference in the prevention of cisplatin-induced nephrotoxicity when patients were treated with sodium loading alone or with sodium loading with mannitol. No differences were detected in average decrease in creatinine clearance, incidence of nephrotoxicity, or rates of hypomagnesemia and hypokalemia. The difference in time to resolution of toxicity appeared to be significant, however there were limitations in evaluating this outcome.

Purpose The aim of the study was to analyze patients' busulfan (BU) exposure after oral administration of extemporeanously prepared BU capsules prior to blood stem cell transplantation.

Methods Patients were treated with 1 mg/kg body weight BU administered orally every 6 h on each of 4 consecutive days prior to blood stem cell transplantation. Each BU dose was administered in 1 gelatine capsule to be swallowed and containing the individually calculated dose of pure BU active substance. Blood samples were obtained from 6 adult patients 0, 30, 60, 90, 120, 180, 240, 300, and 360 min after the 1st, 5th, and 13th BU dose, frozen and analyzed subsequently by using a HPLC assay with UV detection. In addition, in two patients concomitant TDM was executed. BU exposure was monitored concurrently and BU doses were targeted to achieve a steady-state plasma concentration (C_SS) of 600–900 ng/mL or 900–1100 ng/mL depending on the underlying disease. In these patients blood samples were obtained 0, 60, 120, 180, 240, and 360 min after the 1st, 5th, 9th, and 13th BU dose and analyzed concurrently.

Results For the six patients monitored retrospectively, the time to reach peak plasma BU concentration (C_max) ranged from 1 to 5 h (mean 2.4 h). BU C_max – values varied from 728 to 1807 ng/mL (mean 1174 ng/mL), and BU clearance (CL/F) from 2.32 to 3.75 mL/min/kg (mean 2.97 mL/min/kg). The mean BU steady state (C_SS) concentration calculated was 973 ng/mL (range 754–1226 ng/mL) with a mean AUC of 5818 ng·h/mL (range 4521–7171 ng·h/mL). One of the two patients receiving targeted BU doses required an upward dose adjustment. None of the eight patients suffered from vomiting during BU therapy.

Conclusions BU active substance encapsulated without further excipients in gelatine capsules is highly suitable for oral BU therapy. However, therapeutic drug monitoring and BU dose adjustment is still advisable to achieve optimal systemic BU exposure in each individual patient.

Introduction. Antineoplastic drug therapy errors represent a high iatrogenic potential due to antineoplastic drugs narrow therapeutic ranges and the complexity of chemotherapy regimens that may increase the risk of morbidity and mortality for oncology patients.

Setting. We report a 57-year-old man with head and neck cancer who mistakenly received 180 mg/m² of cisplatin overdose despite the safety measures and validations carried out during preparation. The patient developed moderate nausea and vomiting, acute renal failure, hearing difficulty (tinnitus), and severe myelodepression.

Patient management. Prophylactic and symptomatic treatments were applied in order to prevent and correct toxicity during the 9 days stay at hospital.

Result. He recovered with mild tinnitus and mild renal impairment as the only sequelae. This case presents a hospital stay and treatment quite different to others used to reverse all cisplatin overdose toxicity and it shows the benefits of prompt management.

Capecitabine is an oral pro-drug of fluorouracil, which is a commonly used cytotoxic drug in the treatment of colorectal carcinoma. Many adverse effects are known to occur with capecitabine including diarrhea, palmar-planter erythrodysesthesia and nausea. We report a case of capecitabine-induced pancreatitis, also occurring with re-challenge.

Background. Heparin-induced thrombocytopenia (HIT) is a serious adverse effect associated with heparin therapy. Current laboratory confirmation for immune mediated HIT often results in false positives and unnecessary treatment, exposing individuals to possible complications. As a result, clinical evaluation has been recommended in conjunction with laboratory testing. We hypothesize that utilization of a clinical scoring scale, the 4T’s, will result in the initial appropriate therapy for suspected HIT.

Methods. This is a retrospective chart review of 108 patients who underwent ELISA testing for HIT at a university hospital. The 4T’s scale was applied, stratifying individuals into low, intermediate, and high-risk categories. Each risk score was compared to the ELISA results to determine if the 4T’s can predict the diagnosis of HIT and result in appropriate management. ELISA optical density scores as well as incidence of adverse events were also compared among risk categories.

Study Results. Individuals with low risk correlate with a negative ELISA compared to intermediate and high-risk individuals (p = 0.01 and p < 0.01) and also were significantly more likely to predict institution of appropriate therapy (p < 0.01). Median optical density scores were 0.184 (0.046--2.116), 0.226 (0.067--1.887), and 0.476 (0.096--1.309) for low, intermediate, and high 4T scores. Major adverse events include thrombosis and bleeding.

Conclusions. Individuals with low risk were more likely to receive initial, appropriate therapy and were also significantly more likely to have a negative ELISA test result. Individuals with low risk determined by the 4T score therefore may have therapy and serologic testing for HIT withheld.

Objective. To analyze medication errors (MEs) in a multidisciplinary system with a Computerized Pharmacotherapy Process (CPP) in cancer patients.

Design. A longitudinal, prospective 2-year (January 2003 –to December 2004) cohort study was made in adult patients administered antineoplastic treatment in Services of Oncology and Haematology. MEs were identified by double cross-validation of each stage of the pharmacotherapeutic process (prescription, preparation, dispensing, administration, and follow-up) carried out by the multidisciplinary team (physician, pharmacist, nurse) with CPP assistance.

Variables. Number of MEs per 1000 patient-days, percentage according to the stage of the pharmacotherapeutic process and the severity of intercepted ME (scored from 1 = no damage to the patient, to 5 = patient death).

Results. A total of 1311 patients were receiving treatment, and MEs were identified in 225. Out of a total of 13,158 patient-days, 276 MEs were detected, equivalent to 20.9 MEs per 1000 patient-days; of these, 16.8 MEs per 1000 patient-days (80%) were intercepted and did not affect any patient.

The detected ME distribution according to pharmacotherapeutic stage was: prescription 75.7%, preparation 21.0%, dispensing 1.8%, administration 1.1%, and follow-up 0.4%. ME distribution according to severity was: grade 1 : 15.9%, grade 2 : 49.6%, grade 3 : 33.7%, grade 4 : 0.7%, and grade 5 : 0%.

The system intercepted 98.9% of all MEs with severity ≥3 (MEs with a potential for causing patient damage).

Conclusions. The multidisciplinary system with a well-established CPP detects 20.9 MEs per 1000 patient-days and intercepts 98.8% of all MEs with a potential for causing patient damage.

We report a hemifacial paralysis as an adverse drug reaction possibly related to the use of omeprazole in a patient with acute lymphoblastic leukemia. We believe that this case, although very rare, is clinically significant and worth mentioning, owing to the frequent use of omeprazole in the oncology setting.

Purpose. The aim of this study was to determine the loading efficiency, physicochemical stability, and release of irinotecan-loaded DC Beads^TM (bead size 100–300 µm, 300–500 µm) before and after mixing with nonionic contrast medium (Accupaque® 300, Imeron® 300, Ultravist® 300) during a prolonged period of time (28 days) when stored at room temperature or refrigerated.

Methods. DC Beads^TM were loaded with 50 mg irinotecan (Campto®) per milliliter beads in a 2 h loading period. Drug loading efficiency and stability were determined by measuring the irinotecan concentration in the excess solution. A free-flowing in vitro elution method for a period of 2 h and phosphate buffered solution (PBS, pH 7.2) as elution medium were used to analyze the integrity of the irinotecan-loaded. Stability of irinotecan-loaded beads after mixing with an equal volume of three different nonionic contrast agents was determined by measuring irinotecan concentrations in the excess solutions. Vials with loaded beads were stored protected from light at room temperature. Mixtures with contrast media were stored protected from light under refrigeration (2–8°C). Samples were taken periodically over a 4 week period (day 0, 1, 3, 7 and 28). A reversed phase HPLC assay with ultraviolet detection was utilized to analyze the concentration and purity of irinotecan.

Results. The loading procedure of DC Beads^TM with irinotecan drug solution resulted in a loading percentage of 96% (bead size 100–300 µm) independent of the storage time. No differences in loading levels and no irinotecan degradation products were observed over the period of 28 days, while the test vials were stored light protected at room temperature. Integrity of loaded irinotecan was also given over that same period of time according to the purity and concentration of irinotecan measured after intentional elution with PBS. Mixing of irinotecan-loaded beads (bead size 100–300 µm, 300–500 µm) with nonionic contrast media decreased the irinotecan loading efficiency by ~5–10% during a maximum period of 24 h. However, no further elution or degradation was observed during a 4-week period when stored protected from light under refrigeration.

Conclusions. Irinotecan-loaded DC Beads^TM are shown to have adequate physicochemical stability over a period of at least 28 days when stored light protected at room temperature. Due to concerns of microbiological overgrowth refrigeration should always be considered. The preparation of admixtures of irinotecan-loaded beads with contrast medium in centralized cytotoxic preparation units is not recommended, because of rapid elution of 5–10% of irinotecan from the loaded beads. Furthermore, physicians see no advantages of admixtures due to the wide variation of mixing ratios of drug-loaded beads with contrast medium. In addition varying volumes of 0.9% sodium chloride solution are to be admixed during the chemoembolization procedure.

Background. Glomerular filtration rate (GFR) is often used to determine initial dosing of renally excreted cancer drugs. GFR can be calculated using the Cockcroft-Gault (CG) or the modified diet in renal diseases (MDRD) study formulas, both of which are based on serum creatinine levels. The MDRD formula is more accurate in noncancer patients, does not require patient weight, and is reported automatically by all laboratories in British Columbia, Canada. We previously showed that the CG and MDRD formulas have similar accuracy for carboplatin dosing in patients with gynecological malignancies. We now examine dosing of all renally excreted cancer drugs in the general cancer population. Since this setting does not include routine measurement of GFR, we report the concordance of estimates of GFR derived from the CG and MDRD formulas.

Methods. Patient data were collected retrospectively at the BC Cancer Agency. The primary outcome was the proportion of patients who would have received a different initial dose due to difference in the GFR. Each patient’s dose was determined from dose adjustment tables stated in specific treatment protocols. The secondary outcome was concordance of the GFR derived from CG and MDRD, using the method of Bland and Altman. A difference of >30% was assumed to be clinically significant because this difference would usually lead to dose adjustment based on reclassification of renal function.

Results. A total of 313 patients were evaluated, with 40% male. The median age was 56 years, weight 67.5 kg, height 166 cm, and serum creatinine 74 µmol/L (0.84 mg/dL). The median GFR derived from the CG and MDRD formulas were 86.8 mL/min (mean 91 mL/min, SD ± 30 mL/min) and 87.6 mL/min (mean 88 mL/min, SD ± 26 mL/min), respectively. A total of 86% (27/313) of patients would have received a different dose due to difference in the GFR; of these, 67% (18/27) would have received a higher dose. A difference of >30% in GFR was found in 17.9% (56/313) of patients.

Conclusions. There is good concordance of the GFR derived from the CG and MDRD formulas for most cancer patients, with less than 10% of patients expected to receive a different initial dose of chemotherapy. The MDRD formula may be a reasonable alternative to the CG formula for dosing of cancer drugs which are renally excreted or nephrotoxic.

Objective. To highlight the patient care activities performed by pharmacists during their ward rounds in medical oncology ward of a tertiary care hospital in western region of Nepal.

Methods. The study was conducted for 3 months. Two pharmacists joined the clinicians and nurses in the ward rounds every morning as a member of healthcare team. The data used in this study was obtained from different documented files in hospital and were analyzed as per study objectives.

Results. During 3 months (May 20, 2008 to August 20, 2008), pharmacists provided answers to eight queries asked by clinicians and nurses for the patient care purpose. During the same period pharmacists detected four cases of medication errors and provided suggestions on them. A total of 30 adverse drug reaction (ADR) reports were reported to the regional pharmacovigilance center during the study time. Altogether there were 84 types of adverse drug reaction seen on those patients. Most of them were related to hematological system.

Conclusion. The study evaluated the drug information provided by pharmacists, spontaneous reporting of ADRs by the pharmacists, and their intervention on treatment plan of patients during ward round. This suggests pharmacists can play a significant role on patient care when he or she joins round with other healthcare personnel in the oncology ward.

Objectives. Initial androgen deprivation therapy (ADT) for metastatic prostate cancer with combined androgen blockade (luteinizing-hormone releasing hormone agonist [LHRH agonist] plus antiandrogen) is not recommended in British Columbia (BC). However, this is difficult to monitor since ADT includes concurrent antiandrogen for the first month of LHRH agonist to prevent disease flare. We describe the prevalence of CAB use in BC and its financial impact.

Methods. This was a population-based, retrospective analysis. Patients started on LHRH agonist in January 2005 to December 2006 were identified from the BC Cancer Agency database. CAB was defined as greater than 1 month of antiandrogen concurrently with LHRH agonist. Incremental cost of CAB was based on an average 18 months of therapy from the pivotal CAB study. Incremental cost-effectiveness ratio (ICER) was based on life-year gained (LYG) from the Prostate Cancer Trialists’ Collaborative Group meta-analysis. Estimated financial impact for 2007–2008 was based on an annual increase by 5.5% in prevalence of prostate cancer in BC.

Results. A total of 2751 patients were identified. CAB was used in 607 patients (22%), associated with an incremental cost of CDN$1768 and ICER of CDN$11,220/LYG per patient. Total incremental cost was CDN$1,073,176 and estimated to be CDN$1,398,644 for January 2007 to December 2008.

Conclusion. Nearly one-quarter of patients were treated with CAB for metastatic prostate cancer even though it was not recommended in BC. Additional cost of CAB use was considerable, at CDN$1768 per patient. With increased prevalence of prostate cancer, this has important budget implication for funding agencies which do to recommend CAB.

Objective. To review the pharmacology, pharmacokinetics, efficacy, and safety of two new thrombopoietic (TPO) receptor agonists, romiplostim and eltrombopag, in the treatment of chronic idiopathic thrombocytopenic purpura (ITP) in adults.

Data sources. A MEDLINE search was conducted (1966 to March 2009) using the search terms romiplostim, AMG 531, eltrombopag, SB-497115, idiopathic thrombocytopenic purpura. Articles on phases 1–3 clinical trials in patients with ITP were identified and reviewed. References from manufacturer information, and abstracts from recent hematology meetings, were also evaluated.

Study selection and data extraction. Controlled clinical trials evaluating romiplostim and eltrombopag for treatment of chronic ITP in adults were selected from the data sources. All published relevant abstracts were also included.

Data synthesis. Limited randomized controlled trials and open-label ongoing long-term extension studies for romiplostim and eltrombopag, have<continued/>shown that both TPO agonists are effective in improving the platelet count and reducing the bleeding episodes in adult patients with ITP unresponsive to at least one standard treatment. The most common adverse events associated with the drugs are mild to moderate headaches. The use of these agents has also been associated with rare but serious side-effects including bone marrow reticulin fibrosis, thrombotic events, and myeloid malignancies.

Conclusions. Until more long-term follow-up data regarding the safety, as well as comparative studies that further define the role of TPO agonists versus other agents in the treatment of chronic ITP are available, these agents should be reserved for patients with ITP refractory or intolerant to standard therapy.

Purpose. This study describes the efficacy of aprepitant in preventing nausea and vomiting associated with high-dose chemotherapy in hematopoietic stem cell transplant (HSCT) patients. Our hypothesis is the addition of aprepitant to 5-HT3 antagonists and dexamethasone would result in a 20% increase in complete response (CR) rates compared to CR rates from published studies evaluating antiemetic regimens without aprepitant.

Methods. Adult HSCT patients receiving high-dose chemotherapy and aprepitant as part of their antiemetic regimen were included following written informed consent. CR was defined as no emesis, none to mild nausea, and no breakthrough antiemetic use. Daily patient diaries were used on days 1 through 7 following high-dose chemotherapy to collect severity of nausea, emetic episodes, breakthrough antiemetic use, and any antiemetic related side effects.

Results. We accrued a total of 42 patients. CR rates ranged from 42.9% to 73.8% for the 7 days. The average CR rate for days 1 through 7 was 54%. Fourteen patients (33%) maintained a complete emetic response on each of the 7 days. The average CR rate for published studies in HSCT patients receiving an antiemetic regimen without aprepitant is 57%. Most common adverse effects reported by patients receiving aprepitant were hiccups (33%) and drowsiness (33%).

Conclusions. The addition of aprepitant failed to meet our primary endpoint of increasing CR rates by 20%. The lower than expected CR rate was attributed to use of breakthrough antiemetics. Aprepitant did result in preventing emesis in the majority of patients and was associated with minimal side effects.

Oxaliplatin is a unique platinum derivative with anti-tumor activity in a number of malignancies, with neurotoxicity being a frequent side effect. Neurotoxicity can manifest in an acute phase and a chronic phase. The acute phase usually presents as dysesthesias of the hands and feet, jaw tightness, and pharyngolaryngo-dysesthesia, triggered and exacerbated by physical contact with cold temperatures. Although various other symptoms have been reported in the literature, little details are available. We report here, in detail, a case of blepharoptosis which appeared after repeated oxaliplatin infusions, and the disappearance of which seemed to be dependent on the infusion rate. 

Background. P-glycoprotein (Pgp) is a drug efflux pump that transports natural products, including taxanes and other chemotherapeutic agents, from cells. Several frequent polymorphisms in ATP binding cassette gene B1 (ABCB1) may influence Pgp levels and drug efflux. The purpose of this review was to assess the clinical significance of ABCB1 polymorphisms in oncology.

Methods. Peer-reviewed studies were identified through a search of PubMed/MEDLINE (1990–2008) and the ASCO abstracts (2003–2008) database. Included studies described clinical trials where ABCB1 genotyping was performed in patients with cancer. Search terms included ABCB1, Pgp, docetaxel, paclitaxel, irinotecan, imatinib, and anticancer agent. Studies were excluded if the manuscript was not available in English.

Results. The influence of polymorphisms in ABCB1 2677G > T/A, 3435C > T, and 1236C > T and progression-free and overall survival in 309 patients from the Australian Ovarian Cancer Study treated with paclitaxel/carboplatin demonstrated that compared to homozygote GG carriers at 2677, women with the minor T/A alleles were significantly less likely to relapse following treatment. Other trials of ABCB1 genotyping in breast and prostate cancer patients receiving taxanes have shown inconsistent results. Pharmacokinetic studies where ABCB1 was genotyped and patients received irinotecan or imatinib have also shown inconsistent results.

Conclusion. A number of commercially available drugs are substrates for Pgp, and the ABCB1-variant genotypes are frequent and functionally significant, which may have future implications for drug dosing. 

Study objectives. Hospitalized cancer patients are at an increased risk for venous thromboembolism (VTE) and it is recommended they receive pharmacologic prophylaxis unless otherwise contraindicated. The majority of data supporting this recommendation comes from sub-group analyses and extrapolation of data gathered in general medical/surgical patients. This study seeks to assess the safety and efficacy of VTE prophylaxis in cancer patients admitted to our institution.

Methods. Charts of patients 18–89 years of age receiving VTE prophylaxis with unfractionated heparin, low molecular weigh heparin, or fondaparinux while admitted to Karmanos Cancer Center between September and October 2007 were retrospectively reviewed. Risk factors for VTE were assessed and the efficacy/safety of the prophylactic agents was compared.

Results. One-hundred and eighty consecutive patients were identified. The average number of risk factors for developing VTE was 3–4 per hospital admission in addition to an active cancer diagnosis. Three VTEs occurred in the heparin group with two patients experiencing a VTE during their admission and one experiencing a VTE within 1 month after discharge. Four (2.6%) patients receiving heparin had a major bleeding event. Minor bleeding occurred in 14.3, 11.5, and 22.2% of patients receiving heparin, enoxaparin, and fondaparinux, respectively.

Conclusions. This retrospective study showed cancer patients are at increased risk for VTE, typically with 3–4 risk factors per admission. VTEs were uncommon; however, three patients receiving heparin experienced a VTE and four had a major bleeding event. Minor bleeding rates were similar among groups.

Purpose. With the emerging new warnings surrounding the use of erythropoiesis–stimulating agents (ESAs), the pharmacist's role as health educator and risk communicator expands further to include patient scrutiny to check for eligibility and patient monitoring to check for response or toxicity. This review explores the benefits and risks linked to ESAs use, and the proposed role.

Summary. ESAs have been increasingly used for the treatment of chemotherapy–induced anemia because of its documented effect on decreasing transfusion dependency. However, their use has been associated with thromboembolic complications, tumor progression, and decreased overall survival. This review covers current recommendations and guidelines that surround ESAs use in the supportive care of cancer patients.

Conclusion. To minimize or prevent the complications associated with ESAs use, cancer patients should be adequately monitored and counseled. This highlights the importance of the pharmacist's involvement to optimize patient care.

Objective. To determine the pharmacokinetic (PK) profile of granisetron transdermal formulation and examine its possible relationship with age, gender, and renal function.

Methods. This article describes a Phase I PK study and a post hoc pooled population PK analysis. The Phase I study was a randomized, cross-over study that assessed PK parameters of three granisetron patch sizes and oral granisetron. The pooled population PK analysis included data from three trials in healthy subjects (n = 48) and from Phase II and III studies in patients with cancer (n = 793). The population PK model was used to investigate granisetron exposure and its possible relationship with age, gender, and renal function.

Results. Following oral dosing, plasma granisetron concentration was quantifiable at 1 h, and maximal mean concentration (4.7 ng/mL) was reached 2 h after administration. With transdermal application, maximal concentration was reached 48 h post-application; t_1/2 was 36 h. With oral dosing, overall exposure after 5 days was 306 ng/mL·h, and C_avg 2.6 ng/mL. This corresponded to an AUC_0– for the 52 cm² patch of 420 ng/mL·h and C_avg 2.2 ng/mL over 6 days. Clearance was not affected by age, gender, weight, or renal function.

Conclusion. The 52 cm² granisetron patch achieves a similar exposure to that of a 2 mg oral dose and provides continuous delivery of granisetron over 6 days. The patch may have utility in treating chemotherapy-induced nausea and vomiting where prolonged drug delivery is advantageous. No dose adjustments would be needed based on age or renal function.

Cefepime, a fourth generation cephalosporin, is widely used in hematology and oncology patients. These patients may require plasma exchange (PE) for indications such as chemotherapy- or cancer-induced thromobotic thrombocytopenic purpura to name a few. To date, no pharmacokinetic evaluation has been conducted assessing cefepime's disposition during PE. A 2 g IV cefepime single dose was given to patients undergoing therapeutic PE. Two hours from cefepime dose administration, plasma concentration was measured. PE was then instituted and cefepime plasmapheresate concentration was measured at the completion of the PE session. Cefepime levels were measured using HPLC. The percentage removed by PE was calculated as: amount removed/2 g dose. Ten adult patients were analyzed: median age (range): 52 years (33–67) and median weight (range); 82.85 kg (47–120). PE indications were: myasthenia gravis (n = 3), transverse myelitis (n = 2), multiple sclerosis (n = 1), chronic inflammatory demyelinating polyneuropathy (n = 1), idiopathic thrombocytopenic purpura (n = 1), thrombotic thrombocytopenic purpura (n = 1), and humoral rejection post cadaveric renal allograft (n = 1). All patients except one had a creatinine clearance >60 mL/min. One patient was excluded from the pharmacokinetic analysis owing to loss of venous access during PE. For the remaining nine patients, total plasma volume removed was 3.5 L (range: 2.5–3.5) and duration of PE was 120 min (range: 94–209). The cefepime removed by PE was 3.7% (range: 2.1–6.7). A strong correlation was found between cefepime plasma concentration prior to PE and the amount of drug removed (r = 0.96, r² = 0.92; p < 0.05). The above results suggest that, under the studied conditions, cefepime removal by PE is clinically insignificant (~4% of total 2 g dose).

Background. Pregnancy-associated (PA) breast cancer is a rare disease state that poses unique management challenges, specifically controlling the cancer and maximizing the survival of the expectant mother balanced with the health and safety of the developing fetus. As more women delay pregnancy into their 30s and 40s it is expected that this may become a more important clinical problem in the future. Existing data on PA-breast cancer comes from case series using older chemotherapy drugs. A review of practice was carried out to assess current experience with PA-breast cancer, particularly relating to current cytotoxic drugs and targeted agents.

Methods. The St James's Hospital breast cancer registry, a prospectively maintained database, was used to identify cases of PA-breast cancer over a 6.5-year period and a chart review carried out. Chemotherapy administered during pregnancy, breast cancer specific outcomes, and fetal outcomes were assessed.

Results. Five patients were identified with PA-breast cancer; median age 34 years (range 28–35). The median gestation at presentation was 18 weeks (range 14–29). Four women received chemotherapy during pregnancy; three received doxorubicin and cyclophosphamide (AC) and one paclitaxel. These agents were generally well tolerated. At median gestation of 36 weeks (range 35–40 weeks) four elective caesareans and one spontaneous delivery occurred. There were no fetal abnormalities.

Conclusions. Common cytotoxics can safely be delivered in pregnancy. Further research on newer therapies such as trastuzumab is needed.

Introduction. Capecitabine is an oral prodrug of 5-fluorouracil (5-FU) chemotherapy and is licenced for the treatment of breast and gastrointestinal cancers. Multifocal inflammatory leukoencephalopathy has been associated with intravenous 5-FU, but only a few cases of capecitabine-induced encephalopathy have been reported.

Setting. We describe here a case of encephalopathy following administration of Epirubicin/Cisplatin/Capecitabine chemotherapy, review those cases previously described and suggest recommendations for management.

Results. Symptoms of neurotoxicity from 5-FU and capecitabine usually include confusion, ataxia, nystagmus, dysarthria, sensory loss, and memory loss. Withdrawal of the drug generally leads to improvement of symptoms and steroids are of only questionable benefit.

Conclusion. Patients on fluouropyrimidine drugs with new neurological symptoms should be investigated with brain MRI scan and the drug should be withdrawn until symptoms resolve. Dihydropyrimidine dehydrogenase deficiency should be excluded and ideally an alternative chemotherapy regime sought. We would encourage reporting of such incidences to gain a clearer picture of the incidence and optimal management.

Hiccups generally are self-limiting and of short duration. Those lasting more than 48 h or recurring at frequent intervals are termed persistent. There are numerous causes of hiccups, with medications implicated only rarely. While hiccups are usually benign, severe attacks may lead to exhaustion, eating difficulties, and affect quality of life. We report a case of severe hiccups in a patient receiving chemotherapy (oxaliplatin, 5-fluorouracil, leucovorin) for metastatic colorectal cancer. Hiccups began on the day following chemotherapy and continued constantly for over 30 h until relief was obtained by sucking the juice of a fresh lemonade. A similar pattern occurred in the next two chemotherapy cycles. Dexamethasone had been prescribed as prophylaxis against emesis and this was considered a possible cause. Withholding dexamethasone in the next cycle led to elimination of hiccups without having an impact on control of nausea and vomiting. A number of case reports have linked corticosteroids, particularly dexamethasone, to the occurrence of hiccups. Antineoplastic agents have occasionally been reported as causing hiccups; however, in most of these cases, corticosteroids, as part of the treatment protocol or as antiemetics, may have been a more likely cause. This case serves an as important reminder that adverse effects appearing during chemotherapy may not necessarily be due to antineoplastic agents. In the case of hiccups, oncology health professionals should review all medications and non drug-related factors before assigning causality.

Context. Use of once daily aminoglycosides continues to increase for the pediatric population, including oncology patients. Concerns have been identified and still need to be resolved including the optimal dose, frequency, and monitoring parameters.

Objective. We completed a study to determine if empiric use of gentamicin 7 mg/kg once daily in pediatric patients admitted with febrile neutropenia provided extrapolated peaks and drug-free intervals consistent with suggested preferred levels.

Design. A review of the patient's chart was completed following their discharge from the hospital between September 2006 and October 2007.

Setting. A community hospital.

Patients. A consecutive sample of 17 encounters for pediatric patients admitted for febrile neutropenia that received once daily gentamicin.

Main outcome measures. Extrapolated peak levels and drug-free intervals.

Results. There were seven patients with a total of 17 encounters. The mean extrapolated peak level was 16.9 mg/L. The mean drug-free interval was 15.7 h. Both target peak and drug-free interval were obtained for two encounters (12%), which was one patient.

Conclusion. Gentamicin 7 mg/kg/dose once daily does not provide preferred levels for all pediatric febrile neutropenic patients. Further investigation is required to ensure that once daily gentamicin regimens for pediatric oncology patients provide adequate clinical success.

Background. There is no consensus on a universal dosing method for calculating high-dose chemotherapy in allogeneic Stem Cell Transplant (SCT) patients. The Metropolitan Life (Met-Life) Insurance Company's weight–height tables have been used to determine body weight for chemotherapy dosing for SCT, however no formal study has been done to determine if the Met-Life weight–height tables can be used for chemotherapy dosing in SCT. We retrospectively studied the use of Met-Life weight–height tables for chemotherapy dosing in SCT. Our goal is to determine if patients with extremes of body size who had undergone an SCT and were dosed according to the Met-Life weight–height tables had an increase of Treatment Related Morbidity (TRM) or mortality or relapse.

Patients and Methods. Patients were grouped into three different treatment regimens, cyclophosphamide/TBI, busulphan/cyclophosphamide, and AraC/cyclophosphamide/TBI. Patients in each treatment regimen were further divided into five equal groups based on weight. Treatment related morbidity and mortality was evaluated by comparing the lowest and highest quintiles to the middle quintiles within each treatment regimen.

Result. Data from 262 patients was evaluated in this study. Overall, there was not an increase in TRM or mortality or in relapse in patients with extremes of body size.

Conclusion. The Met-Life weight–height tables could be used to dose patients undergoing allogeneic SCTs. Additional prospective studies would need to be done comparing other chemotherapy dosing methods with the Met-Life weight–height tables to further validate this conclusion.