Journal of Oncology Pharmacy Practice current issue

Initial therapy in multiple myeloma: investigating the new treatment paradigm

Fri, 28 Aug 2009 08:21:59 PDT

The development of three novel chemotherapeutic agents — thalidomide, lenalidomide, and bortezomib — has resulted in a fundamental shift in the management of multiple myeloma. Despite this tremendous advancement, the selection of initial treatment must still be made with a degree of uncertainty as a true standard therapy has yet to be established. Although challenging, the relative abundance of therapeutic options, when taken into consideration with unique patient characteristics, creates the potential for individualization of care.

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.

Nail Toxicity Induced by Cancer Chemotherapy

Gilbar, P., Hain, A., Peereboom, V.-M. — Fri, 28 Aug 2009 08:21:59 PDT

Purpose. To provide a comprehensive literature review of chemotherapy-induced nail toxicity, including clinical presentation, implicated drugs and approaches for prevention and management.

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.

Antineoplastic agent workplace contamination study: the Alberta Cancer Board Pharmacy perspective Phase III

Bigelow, S., Schulz, H., Dobish, R., Chambers, C. R — Fri, 28 Aug 2009 08:21:59 PDT

Objective. To continue with workplace contamination monitoring in the Alberta Cancer Board (ACB) pharmacy practice environment.

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.

Patients' perspectives and safe handling of oral anticancer drugs at an Asian cancer center

Chan, A., Leow, Y. C., Sim, M. H. — Fri, 28 Aug 2009 08:21:59 PDT

Background. In view of the increased usage of oral anticancer drugs in the contemporary treatment of cancer, we aimed to examine cancer patients’ perspectives of oral anticancer drugs, through a survey at an Asian cancer centre. This study also intended to describe patients’ behavior regarding storage, handling, and administration of oral anticancer drugs.

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.

Retrospective review of hemoglobin and/or hematocrit levels with occurrence of thrombosis in cancer patients treated with erythropoiesis stimulating agents

Fullmer, A. C, Miller, R. — Fri, 28 Aug 2009 08:21:59 PDT

Background. No data exists that directly compares hemoglobin and hematocrit levels between cancer patients with and without occurrence of thrombosis during treatment with erythropoiesis stimulating agents (ESAs).

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.

Modification of vincristine dosing during concomitant azole therapy in adult acute lymphoblastic leukemia patients

Harnicar, S., Adel, N., Jurcic, J. — Fri, 28 Aug 2009 08:21:59 PDT

Objective. Vincristine is an important component in the treatment of acute lymphoblastic leukemia (ALL) and is now the backbone of therapy in the induction and consolidation phases of this disease. Proper dosing of vincristine is required to maximize disease control while avoiding toxicity. The gastrointestinal toxicity of vincristine such as decreased peristalsis can potentially be increased if the CYP 3A4 enzyme is inhibited. This interaction may become more prevalent with increasing use of CYP 3A4 inhibitors such as the azole antifungals. Since azoles are increasingly being used for prophylaxis and treatment of fungal infections in this patient population, an assessment of vincristine dosing and toxicity is the first step to constructing guidelines for the coadministration of these agents.

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.

Rapid Infusion Rituximab Changing Practice for Patient Care

Al Zahrani, A., Ibrahim, N., Al Eid, A. — Fri, 28 Aug 2009 08:21:59 PDT

Rituximab is a chimeric anti-CD20 monoclonal antibody. Its intravenous administration is associated with substantial infusion related-toxicity. Recommended infusion durations are prolonged (average 5—6 h for first infusion and 3—4 h for subsequent infusions). We aimed to explore the safety and tolerability of short infusion rituximab, (over 90 min), in Non-Hodgkin’s lymphoma patients at Riyadh Military Hospital. Adult oncology patients diagnosed with Non-Hodgkin’s lymphoma, who were to receive rituximab, were included in the study. The schedule of administration for cycle one was unaltered and delivered according to the product monograph (5—6 h). All subsequent cycles were administered over a total infusion time of 90 min (20% of the dose in the first 30 min then the remaining 80% over 60 min, total dose delivered in 500 mL sodium chloride). All patients were observed for infusion related reactions during the rituximab infusion and for 30 min after the infusion. In addition, all patients were advised to report any reaction occurring within 24 h after rituximab infusion.

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.

Immediate cross-hypersensitivity between Micafungin and Caspofungin: A case report

Fri, 28 Aug 2009 08:21:59 PDT

A hematopoietic stem cell transplant patient with a history of immediate drug hypersensitivity reaction to micafungin was considered for a caspofungin trial. A caspofungin intradermal skin test was performed. The result was positive, suggesting the presence of cross-reactivity and that the cyclic peptide nucleus chemical structure shared between echinocandins is the site of IgE recognition. It is recommended to avoid challenging patients with history of immediate hypersensitivity to one echinocandin with another.