For patients eligible for autologous stem cell transplantation, various combinations of novel agents with dexamethasone or traditional chemotherapy have supplanted the previous standard regimen consisting of vincristine, doxorubicin, and dexamethasone. In elderly patients or others that are deemed ineligible for the transplant procedure, the addition of a novel agent to melphalan-prednisone has demonstrated significant improvements in response rates. Due to the immaturity of the available data, it is perhaps best to regard the era of novel agents with a degree of rational enthusiasm, as the ultimate impact on patient care remains undetermined. Although further research is clearly implicated, recent advancements have resulted in significant progress toward obtaining optimum outcomes in a historically challenging disease.

Data sources. A search of MEDLINE and EMBASE (1966—2008) databases was conducted using the terms (and variations of the terms) antineoplastic agents, nails, nail toxicity, onycholysis, and paronychia. Bibliographies from selected articles were reviewed for appropriate references.

Data extraction. The retrieved literature was reviewed to include all articles relevant to the clinical presentation, diagnosis, incidence, prevention, and treatment of chemotherapy-induced nail toxicity.

Data synthesis. Nail toxicity is a relatively uncommon adverse effect linked to a number of chemotherapeutic agents. Clinical presentation varies, depending on which nail structure is affected and the severity of the insult. Nail changes may involve all or some nails. Toxicity may be asymptomatic and limited to cosmetic concerns, however, more severe effects, involving pain and discomfort can occur. Taxanes and anthracyclines are the antineoplastic drug groups most commonly implicated. It is suggested that the administration schedule may influence the incidence of nail abnormalities, for example reported cases linked to the weekly administration of paclitaxel.

Before instituting chemotherapy, patients should be educated regarding potential nail toxicities and strategies for prevention implemented. Management includes appropriate nail cutting, avoiding potential irritants, topical, or oral antimicrobials, and possibly cessation or dose reduction of the offending agent. Cryotherapy, through the application of frozen gloves or socks, has been beneficial in reducing docetaxel-induced nail toxicity and may be effective for other drugs. J Oncol Pharm Practice (2009) 15: 143—155.

Setting. The ACB in the Canadian province of Alberta which includes two public tertiary centers and 19 associated community satellite sites based around the province in existing hospitals.

Methods. After the completion of a Phase 1 and Phase 11 study,¹ which investigated the feasibility of routine monitoring of antineoplastic agent contamination in the pharmacy practice environment, it was decided to launch a Phase III study. The Phase III study would be done at the Cross Cancer Institute in the main pharmacy department as well as at a brand new satellite pharmacy within the CCI hospital. Samples would be taken in these areas as well as on the outer exterior of latex gloves worn to prepare cyclophosphamide and other antineoplastics.

Results. The result determined that the area in front of the biological safety cabinet in the main CCI pharmacy department as well as the exterior of the latex gloves showed evidence of cyclophosphamide contamination. The results from the sample taken in the new satellite pharmacy showed no evidence of cyclophosphamide contamination.

Conclusion. Results from this study prompted a decision to launch a Phase IV study to determine the feasibility within our network, for routine monitoring as well as sampling throughout the clean room beyond the BSC.

Methods. This cross sectional survey was conducted at a single site. The interviewer-administered survey was undertaken at the outpatient pharmacy of National Cancer Centre Singapore (NCCS), the largest ambulatory cancer center in Singapore, between January and March 2008. Eligible patients had received at least one cycle of oral anticancer agent treatment or had been taking oral anticancer agents continuously for 3 months.

Results. A total of 126 patients were surveyed. Median age of surveyed patients was 58 years (range 31—85 years). The drugs involved were capecitabine (39.7% of patients), tamoxifen (23.1%), aromatase inhibitors (18.2%), gefitinib (9.1%), and imatinib (3.3%). Over 90% patients self-administered their oral anticancer drugs. The majority of the patients (94.2%) reported no difficulties in adherence to their oral anticancer treatment regimens. Forty per cent of patients reported habitually washing their hands after administering their anticancer drugs. None of the patients, except two patients receiving capecitabine, indicated that they habitually used gloves to handle their oral anticancer medications. Conclusion. The majority of patients receiving oral anticancer agents reported no difficulty in adhering to their oral anticancer treatment regimens as prescribed. However, this survey demonstrated the need to improve patients’ understanding of the requirements for storage, handling and safe administration of oral anticancer drugs.

Objective. To determine the association of hemoglobin and hematocrit levels with the occurrence of thrombosis in cancer patients treated with ESAs.

Methods. A retrospective case-control study approved by the Institutional Review Board was conducted on cancer patients billed for epoetin or darbepoetin between 1 July 2002 and 30 June 2007. Cases were defined as patients billed for thrombosis while controls were defined as patients not billed for thrombosis.

Results. Sixteen patients had an occurrence of thrombosis (cases) and were matched to 16 patients that did not have an occurrence of thrombosis (controls) based on age, sex, and cancer type. The mean peak hemoglobin levels for cases and controls were 12.6 ± 1.2 g/dL versus 12.6 ± 1.4 g/dL (p = 0.9). The mean peak hematocrit levels for cases and controls were 37.3 ± 3.8% versus 37.9 ± 4.3% (p = 0.8). For the 16/586 (2.7%) patients with thrombosis, the mean hemoglobin and hematocrit at time of thrombosis were 9.6 ± 1.0 g/dL and 28.9 ± 3.1%. A significant identifiable risk factor for thrombosis between the cases and controls was history of thrombosis 31.3% versus 0% (p = 0.04). Conclusion. There was no statistical difference in peak hemoglobin and hematocrit levels between patients with thrombosis and those without thrombosis. Further study is warranted to determine if these levels are true risk factors for thrombosis.

Methods. ALL patients !18 years of age receiving vincristine-based therapy from August 2003 through December 2007 with or without azole therapy were included. Data was collected using electronic patient medical records and the pharmacy system (RxTFC). Information was entered into a database for this retrospective study. Patients were separated into two arms; vincristine with azoles and vincristine only. Patient demographic information, chemotherapy regimen, vincristine-induced symptoms, and concurrent strong CYP 3A4 inhibitors and inducers were collected.

Results. A total of 50 patients received vincristine of which 29 (58%) had concurrent azole therapy. No patients received concurrent major CYP 3A4 inhibitors and the baseline characteristics were similar between groups. Vincristine dosing modifications were more common in the azole group (58.6 vs. 23.8%; p = 0.02). The mean dose reduction of vincristine when combined with an azole was 46.5%. Symptoms of decreased peristalsis were more common in patients receiving azoles (65.5 vs. 28.6%; p = 0.019) and on average occurred after the second vincristine dose. Symptoms occurred in 50, 75, and 66.6% of patients receiving fluconazole, voriconazole, and posaconazole, respectively. Patients were more likely to have an incomplete course of vincristine when receiving azole therapy (48.3 vs. 9.5%; p = 0.004).

Conclusion. Caution should be used with the coadministration of vincristine and azoles. It is recommended that institutional guidelines be developed to standardize care for patients receiving vincristine with azole therapy. Potential measures to avoid this interaction include revisiting azole prophylaxis in this patient group and being judicious in azole selection.

From April 2007 to September 2007, 21 patients with non-Hodgkin’s lymphoma were treated with rituximab-based chemotherapy. A total of 126 infusions were administered with average of 6 infusions per patient. The majority of patients were treated with CHOP—Rituximab or CHOP-like regimen. The 90-min Rituximab infusion schedule was well tolerated with no grade 3/4 infusion related adverse events observed. A rapid infusion rituximab over 90 min is well tolerated and safe when administered as the second and subsequent infusions in the course of therapy. This shortened infusion schedule has resulted in a substantial reduction in resource utilization. Our institution has adopted this as routine practice.

Methods. The clinical and safety data were obtained from a meta-analysis of randomized trials comparing either nab-paclitaxel (260 mg/m² q3wk) or docetaxel (100 mg/m ² q3wk), to standard paclitaxel (175 mg/m² q3wk). Health care resource use for the delivery of chemotherapy and the management of grade III/IV toxicity was collected from the oncology literature. Treatment preferences and health state utilities were obtained from 24 female oncology nurses and pharmacists using the time trade-off technique.

Results. Nab-paclitaxel had the lowest incidence of grade III/IV toxicity. This translated to lower overall costs for managing the grade III/IV events relative to both docetaxel and paclitaxel ($597 vs. $2626 vs. $1227). Using the median number of cycles administered and the cost impact of grade III/ IV toxicity, the overall cost for nab-paclitaxel would be $15,105 compared to $15,268 for docetaxel and $3557 for paclitaxel. When treatment preferences were assessed, 20 of 24 (83.3%) respondents selected nab-paclitaxel as their preferred choice compared to only 4 who selected docetaxel. These corresponded to a gain of 0.203 and 0.016 QALYs for nab-paclitaxel and docetaxel, respectively. With these utility benefits, the incremental cost per QALY gained was more favorable for nab-paclitaxel than docetaxel ($56,800 vs. $739,600).

Conclusions. Nab-paclitaxel would be an economically reasonable alternative to docetaxel in MBC patients. As an alternative to paclitaxel, formulary committees must decide if the $56,800 cost per QALY represents good value in their health care setting. J Oncol Pharm Practice (2009) 15: 67—78.

Methods. The pharmacist met with consenting patients at the initial clinic visit and followed up by telephone two additional times. The pharmacist was available to answer questions outside of clinic hours. Surveys were developed and given to patient and staff to evaluate their experience.

Results. Over 4 months, 13 patients were enrolled. The pharmacist interacted with each patient an average of 9 times with 55% of interactions occurring outside scheduled visits and two-thirds of pharmacist interventions directly involving patient care. A total of 85% of patients and staff responded to the evaluation survey and 90% of respondents indicated that the pharmacist should remain part of the NeuroOncology team. Patients reported less stress related to their treatment and clinical staff experienced improved clinical efficiency directly as a result of the presence of the pharmacist.

Conclusion. Based on these results, a clinical pharmacist should become a permanent member of the outpatient NeuroOncology clinic. J Oncol Pharm Practice (2009) 15: 79—85.

Objectives. The purpose of the paper was to present and analyze five years of medication error prevention survey results, thus summarizing adherence to the Alberta Cancer Board's medication error prevention policies.

Methods. Medication error prevention survey results from 2003 to 2007 were collected. For each of the five years, a medication error prevention survey was faxed to the pharmacy department at each of the 19 cancer centers of the Alberta Cancer Board. Results of the survey were tabulated by the pharmacist responsible for quality assurance.

Results. Analysis of the five years of medication error prevention survey results revealed that over 90% of the medication error prevention policies were followed within the 19 Alberta Cancer Board sites. Adherence to the policies was 490% in the tertiary sites and associate clinics. Adherence was also >90% in the community cancer centers.

Conclusions. Results from the survey indicated that the medication error prevention policies are practiced within the Alberta Cancer Board. Potential areas of improvement have been identified and will be addressed by the Medication Error Prevention Team. J Oncol Pharm Practice (2009) 15: 87—93.

Purpose. This article reviews the preclinical and clinical data on ixabepilone in patients with locally advanced and metastatic breast cancer (MBC) and provides guidance for pharmacists on its optimal use. Data sources. PubMed and conference proceedings through August 2008.

Results. In preclinical studies, ixabepilone has demonstrated potent antitumor activity and low susceptibility to mechanisms that confer tumor resistance. Clinically meaningful benefits have been achieved with ixabepilone monotherapy in phase 2 trials of patients with MBC who have failed previous chemotherapies (anthracyclines, taxanes, or capecitabine). In a randomized, phase 3 trial, the combination of ixabepilone and capecitabine proved more effective than capecitabine alone after the failure of taxane and anthracycline regimens. At the recommended dose and schedule, the therapeutic ratio of ixabepilone is generally favorable, and its adverse effects (notably neutropenia and peripheral neuropathy) are generally manageable and reversible.

Conclusion. Ixabepilone represents an advance in the treatment of anthracycline - and taxane-pretreated MBC. Future studies will define its efficacy in combination with other drugs used in the treatment of MBC, as well as in other types of cancer. J Oncol Pharm Practice (2009) 15: 95—106.

Aim: To report a case of isolated hyperbilirubinemia in a patient treated with cytarabine-based chemotherapy for AML.

Clinical Details. After a diagnosis of AML the patient was admitted to hospital to receive induction chemotherapy consisting of high-dose cytarabine, idarubicin, and etoposide. All baseline laboratory results were normal, except the full blood evaluation that was consistent with AML. The chemotherapy was delivered over 7 days, and on the eighth day the patient had a bilirubin (BL) level of 27 umol/L

(normal range 522 umol/L). All other liver function tests (LFT) were normal. This isolated hyperbilirubinemia remained for the rest of the patient's admission, peaking on day 26, with a level of 255 umol/L. After a stay in the intensive care unit, the patient was discharged on day 45 with a bilirubin level of 33 umol/L. All other LFT remained unremarkable.

Outcome. The isolated hyperbilirubinemia resolved slowly and on day 68, when the patient was re-admitted for further dose-reduced cytarabine, the BL level was 21 umol/L. The patient was successfully retreated with this lower dose regimen.

Conclusion. Isolated hyperbilirubinemia is an uncommon presentation of cytarabine induced liver dysfunction. Resolution does occur but over a prolonged period. A lower dose of cytarabine for future treatment should be considered. J Oncol Pharm Practice (2009) 15: 107—110.

Case Summary. A 69-year-old woman with recurrent, focally anaplastic OTC was given a therapeutic trial of erlotinib, a small molecule inhibitor of epidermal growth factor receptor (EGFR). Formalin-fixed, paraffin-embedded portions of the tumor were analyzed for EGFR expression, and tumor genomic DNA was amplified by polymerase chain reaction (PCR) and subjected to EGFR mutation analysis.

Discussion. An early and dramatic response was achieved with erlotinib. The tumor was focally positive for EGFR by immunostaining and two point mutations were identified, one on exon 18 and one on exon 20 in the tyrosine kinase (TK) domain.

Conclusion. Erlotinib or other novel protein kinase pathway inhibitors should be evaluated further in patients with aggressive thyroid cancer variants, who may exhibit these and perhaps other tyrosine kinase mutations. J Oncol Pharm Practice (2009) 15: 111—117.

Method. A case (of a pregnant woman with newly diagnosed colorectal cancer) is presented to explore this area of medical uncertainty.

Result. Managed by a multi-disciplinary team, successful prolongation of gestation was achieved with an oxaliplatin-based chemotherapy regimen.

Conclusion. A perspective of the ongoing conflict between prolonging the mother's life and preserving fetal development is highlighted. Although not life-saving, administration of chemotherapy in this woman was life-sparing. J Oncol Pharm Practice (2009) 15: 5—8.

Setting. Fifty-two bed medical-surgical intensive care unit of an academic oncology institution. Patients. A convenience sample of 100 medical and surgical critically ill oncology patients who received intensive care for more than 24 hours and at least one dose of a H2RA or PPI for prevention of SRMB.

Interventions. None.

Measurements and Main Results. Patients were followed throughout their intensive care unit stay for the development of an overt and/or clinically significant gastrointestinal (GI) bleed. More patients received a PPI (n = 81) in contrast to a H2RA (n = 19) for SUP. Overall, 94 patients (94%) had at least one risk factor for a SRMB with four patients (4%) experiencing an event (overt bleed, n=3; clinically significant bleed, n =1). All cases of GI bleeding occurred in patients receiving a PPI. No ICU deaths were considered directly related to a GI bleed.

Conclusions. The incidence of SRMB among high-risk critically ill oncology patients receiving SUP appears low; further, large-scale trials are needed to confirm this finding. J Oncol Pharm Practice (2009) 15: 9—16.

Methods. References were obtained through literature searches on PubMed as well as from the Proceedings of Annual Meetings of the American Society of Clinical Oncology, the American Society of Hematology, and European Hematology Association.

Results. Initial studies of dasatinib showed that 70 mg twice-daily resulted in impressive hematologic and cytogenetic responses in patients with all phases of CML and Ph+ ALL. Aside from hematologic events, the most common drug-related toxicities (mostly grade 1—2) in dasatinib clinical trials were fluid retention (including pleural effusion), diarrhea, skin rash, headache, hemorrhage, fatigue, nausea and dyspnea. A Phase III dose optimization study showed that the safety profile of dasatinib is improved and efficacy maintained when administered on a 100 mg once-daily dosing schedule compared with the 70 mg twice-daily schedule in patients with chronic phase (CP) CML.

Conclusion. The safety profile of dasatinib is manageable. A 100 mg once-daily dose is now approved for use in patients with CP CML. A dose of 70 mg twice daily remains the recommended dosage for use in patients with advanced phase CML or Ph+ ALL. J Oncol Pharm Practice (2009) 15: 17—27.

Method. We would like to report four patients with cutaneous reactions resulting from weekly administration of docetaxel.

Results. All cases are heavily pre-treated patients, receiving docetaxel as second or third line therapy. The cutaneous reactions occur at cycle 5. The time between chemotherapy to development of skin lesions is from 1 to 7 days. Lesions usually resolve with desquamation leaving behind areas with hyper-pigmentation or hypo-pigmentation over a period of 2 to 3 weeks. The management strategies include hand elevation, warm or cold compresses, topical and/or systemic antibiotics, topical and/or systemic corticosteroids, and cessation of drug.

Conclusions. There is a need for a systematic approach to manage these cutaneous reactions. Oncology trained pharmacists play vital roles in assessing, managing, documenting and patient education. J Oncol Pharm Practice (2009) 15: 29—34.

Methods. Growth inhibition assays were conducted in six human endometrial cancer cell lines to evaluate the activity of selected anticancer agents with gefitinib compared to each alone. Enzyme linked immunosorbant assay (ELISA) assessed the presence of pEGFR in treated and untreated cells. Evaluation of the suppression of correlative biological targets in the cell-signaling pathway was completed by immunoblotting. RT-PCR was used to characterize the expression of MRP and ABC transport proteins.

Results. This in vitro study gefitinib did not observe cytotoxic activity as a single agent. However, the activity of gefitinib as EGFR inhibitor was confirmed. The combination of gefitinib with paclitaxel and docetaxel exhibited improved in vitro cytotoxic activity compared to each antineoplastic agent alone. Suppression of pAKT and p27 in the human endometrial cancer cells treated with selected combinations of chemotherapeutic drugs and gefitinib was observed.

Conclusion. These data suggest that EGFRinhibitors, such as gefitinib, have the potential to modulate common mechanisms of drug resistance and may have a role in optimizing antineoplastic regimens for the treatment of recurrent endometrial cancer. This may represent a promising option for this class of agents in the treatment of endometrial cancer. J Oncol Pharm Practice (2009) 15: 35—44.

Method. We surveyed selected cancer centers to provide information on their standard volume, drug concentrations, and choice of diluents. MEDLINE was searched for clinical reports using the MeSH terms of `cytarabine,' `methotrexate,' or `thiotepa' with the subheading `Cerebrospinal fluid' and combined with `intrathecal' in all database fields. Data retrieved included the choice of diluent, volume, and/or drug concentration. We evaluated the pH and osmolality of methotrexate (1, 2, 5, and 10 mg/mL), cytarabine (2, 5, 10, and 25 mg/mL), and thiotepa (1, 2, and 5 mg/mL) in normal saline, sterile water for injection (SWFI), and lactated Ringer's solution.

Results. Nine centers were surveyed (seven in Canada, one in Australia, one in United Kingdom). Most centers used 5mL of preservative-free normal saline, irrespective of the drug or drug concentration used. Forty-four reports in the literature were reviewed. Most reported 5 mL of preservative-free normal saline. Most information on drug concentrations was provided for methotrexate, with an average concentration of about 1—2.5 mg/ mL. Cytarabine 0.4—20 mg/mL and thiotepa 1 mg/mL were also reported. In our in vitro evaluation, there was a trend of increased pH associated with increasing concentration of methotrexate and cytarabine. There was no apparent impact of thiotepa concentration on the pH values of the final preparations, irrespective of the diluent used. Except for cytarabine 10 and 25 mg/mL, all the tested solutions have pH within 10% of the physiologic range of CSF. There was a concentration-dependent change in osmolality with methotrexate and cytarabine preparations. Osmolality was increased with increased concentrations in all except methotrexate mixed in SWFI and thiotepa mixed in normal saline and lactated Ringer's solution. Except for some thiotepa solutions, all the tested solutions have osmolality within 10% of the physiologic range of CSF.

Conclusions. There is limited published literature on the potential impact of diluent and drug concentration on the pH and osmolality of IT chemotherapy preparation. Most cancer centers conventionally prepare IT chemotherapy with 5mL of preservative diluent normal saline, irrespective of the specific drug or dose used. The conventional practice means that most methotrexate preparations are likely to have comparable pH and osmolality to CSF. In contrast, cytarabine preparations may show significantly higher pH than the CSF, while thiotepa preparations generally have lower osmolality than the CSF. J Oncol Pharm Practice (2009) 15: 45—52.

Methods. This is a descriptive study of surface contamination with cyclophosphamide, ifosfamide, and methotrexate in two hematology—oncology satellite pharmacies. In order to measure surface contamination with hazardous drugs, samples from four distinct measurement sites within the pharmacy were taken in each of the two phases (pre-and postphases) using a sampling procedure and an analytical method modified from Larson et al.

Results. A total of 133 samples from four measurement sites were taken and analyzed over the course of the study (specifically 60 prephase samples and 73 postphase samples). The study showed a significant increase in the number of positive samples (from 66.7% to 90.4%, p<0.001) from the pre- to the postphase. The increase, however, is only significant in terms of the location where completed preparations were placed after they had come out from under the hood (from 0/15 to 21/28, p<0.001) and the work surface (from 8/15 to 15/15, p = 0.006) and only in terms of ifosfamide. Furthermore, for the other sites studied, the number of positive samples remained unchanged between the pre- and postphase. A statistically significant difference between the pre- and postphase was observed in terms of ifosfamide for three of the four measurement sites studied and methotrexate for one of the four sites. Average concentrations were higher in the post phase in three of the four cases.

Conclusion. This study describes environmental contamination with hazardous drugs in a hospital pharmacy setting before and after reorganizing a hematology—oncology satellite pharmacy. The study showed that a refitting of the hemato-oncology pharmacy is not a sufficient strategy to reduce the environmental contamination by ifosfamide because a significant increase in the number of positive samples from the pre- to the postphase have been observed. Many factors can contribute to influence the contamination of hazardous drugs such as the workflow and the training of the personal. Continuous environmental surveillance of hazardous drugs is required to document traces and help reduce risks. J Oncol Pharm Practice (2009) 15: 53—61.