Ali McBride

National survey on the effect of oncology drug shortages on cancer care

PURPOSE The results of a survey to characterize oncology drug shortages across the United States and the impact of shortages on clinical practice, patient safety, clinical trials, and health care costs are presented. METHODS A 34-item online survey was distributed to 1672 members of the Hematology/Oncology Pharmacy Association and other organizations to gather information on shortages of oncology drugs (i.e., all drugs essential in the care of cancer patients, including supportive care agents). RESULTS Two hundred forty-three completed responses, almost all from pharmacists (97%), were analyzed. Delays in chemotherapy administration or changes in treatment regimens due to drug shortages were reported by 93% of survey participants; 85% of respondents reported increased costs, and 10% reported reimbursement challenges related to drug shortages. At 34% of represented institutions, at least 1000 hours of additional labor annually was needed to manage shortages. Changes in therapy leading to near-miss errors were reported by 16% of participants, with 6% reporting one or more actual medication errors attributable to a drug shortage. The oncology medications most frequently reported to be in short supply during the preceding 12 months were fluorouracil, leucovorin, liposomal doxorubicin, and paclitaxel. The conduct of clinical trials was affected by drug shortages at 44% of represented institutions. CONCLUSION A survey of U.S. oncology pharmacists indicated that oncology drug shortages occurred frequently in the first half of 2011. Shortages led to delays in chemotherapy and changes in therapy, complicated the conduct of clinical research, increased the risks of medication errors and adverse outcomes, and increased medication costs.

Recognizing and managing the expanded risk of tumor lysis syndrome in hematologic and solid malignancies

Tumor lysis syndrome (TLS) is widely recognized as a serious adverse event associated with the cytotoxic therapies primarily used in hematologic cancers, such as Burkitt lymphoma and acute lymphoblastic leukemia. In recent years, TLS has been more widely observed, due at least in part to the availability of more effective cancer treatments. Moreover, TLS is seen with greater frequency in solid tumors, and particularly in bulky tumors with extensive metastases and tumors with organ or bone marrow involvement. The consequences of TLS include the serious morbidity and high risk of mortality associated with the condition itself. Additionally, TLS may delay or force an alteration in the patient’s chemotherapy regimen. The changing patterns of TLS, as well as its frequency, in the clinical setting, result in unnecessarily high rates of illness and/or fatality. Prophylactic measures are widely available for patients at risk of TLS, and are considered highly effective. The present article discusses the various manifestations of TLS, its risk factors and management options to prevent TLS from occurring.

Proteasome inhibitors in the treatment of multiple myeloma

Proteasome inhibition has been shown to be an effective strategy for the treatment of multiple myeloma, as demonstrated by the clinical activity of the first-in-class agent bortezomib. Recently, the second-generation proteasome inhibitor carfilzomib has been approved in the USA in the relapsed and refractory setting, and several other investigational agents are in clinical development, including MLN9708, marizomib, oprozomib and delanzomib. Here, the authors provide a comprehensive review of the key role of proteasome inhibitors in the myeloma treatment pathway, and highlight the similarities and differences in pharmacology, routes of administration, and efficacy and safety profiles between bortezomib, carfilzomib and investigational agents. The authors also evaluate the potential for further improving myeloma treatment through the ongoing development of novel proteasome inhibitors.

Carfilzomib: a second-generation proteasome inhibitor for the treatment of multiple myeloma.

PURPOSE The pharmacology, clinical efficacy, safety, cost, dosage and administration, and place in therapy of carfilzomib for the treatment of multiple myeloma (MM) are reviewed. SUMMARY Proteasome inhibition in MM has become a cornerstone in treatment regimens. Carfilzomib, a second-generation proteasome inhibitor, has demonstrated efficacy in patients with relapsed or refractory disease who have received at least two prior therapies including bortezomib and an immunomodulatory agent. Carfilzomib is an irreversible inhibitor and binds to a different site than bortezomib on the proteasome. A Phase II study evaluated 266 heavily pretreated patients with relapsed or refractory MM who had received at least two prior therapies, including bortezomib and either thalidomide or lenalidomide. The overall response rate was 23.7%, with a median duration of response of 7.8 months. The median overall survival time was 15.6 months. Carfilzomib has a similar adverse-effect profile to bortezomib, including anemia, thrombocytopenia, fatigue, dyspnea, and nausea; however, it does not result in the development or worsening of peripheral neuropathy. Carfilzomib is infused intravenously over 2-10 minutes for 2 consecutive days every week for three out of four weeks, with a 12-day rest period. Dosing is based on the patients actual body surface area. Carfilzomib is available in 60-mg vials for single infusion. The total cost for a year of therapy is approximately

Comparative Evaluation of Single Fixed Dosing and Weight-Based Dosing of Rasburicase for Tumor Lysis Syndrome

155,852. CONCLUSION Carfilzomib, a second-generation proteasome inhibitor that irreversibly inhibits the 26S proteasome, has shown efficacy in clinical studies of patients with relapsed or refractory MM, though the drugs role in the management of MM is not yet clear.

Eribulin mesylate: A novel halichondrin B analogue for the treatment of metastatic breast cancer

To evaluate single fixed dosing versus weight‐based dosing strategies for rasburicase to determine the minimum dose required to mitigate hyperuricemia in the treatment or prevention of tumor lysis syndrome.

Brentuximab vedotin for treatment of non-Hodgkin lymphomas: A systematic review.

PURPOSE The pharmacology, pharmacokinetics, clinical efficacy, safety, and administration of eribulin in patients with metastatic breast cancer are reviewed. SUMMARY Classical chemotherapeutic agents for breast cancer have dominated treatment regimens even in the era of targeted therapy. Disease progression through these agents is often due to the development of resistance or lack of efficacy with these agents. Recently, a new nontaxane agent, eribulin mesylate, was approved for the treatment of metastatic breast cancer in patients who have received at least two prior chemotherapeutic agents. Eribulin is a member of a new class of synthetic cytotoxic agents derived from the Japanese sea sponge Halichondria okadai. Eribulin differs from other antimicrotubule agents in that it can bind to the microtubule cap and inhibit tubulin polymerization, leading to microtubule arrest. In Phase II clinical trials, eribulin demonstrated activity in extensively pretreated patients who had previously received an anthracycline, taxane, and capecitabine and had shown disease progression within the last six months of treatment. In a pivotal Phase III clinical trial of heavily pre-treated patients, patients who received eribulin versus the physicians treatment of choice showed a significant increase in overall and progression-free survival. Eribulin has a manageable adverse-effect profile, consisting mainly of neutropenia and fatigue. Eribulin has been associated with a low incidence of peripheral neuropathy. CONCLUSION Eribulin, a novel synthetic antimicrotubule agent that binds to the vinca domain of tubulin and inhibits the polymerization of tubulin, offers a new treatment option for metastatic breast cancer or locally advanced breast cancer.

Tocilizumab for steroid refractory acute graft-versus-host disease.

BACKGROUND Brentuximab vedotin (BV) is an antibody-drug conjucate (ADC) comprising a CD30-directed antibody, conjugated to the microtubule-disrupting agent MMAE via a protease cleavable linker. BV is FDA approved for use in relapsed classical Hodgkin lymphoma (HL) and relapsed systemic anaplastic large cell lymphoma (sALCL). There are multiple publications for its utility in other malignancies such as diffuse large B-cell lymphoma (DLBCL), mycosis fungoides (MF), Sézary syndrome (SS), T-cell lymphomas (TCL), primary mediastinal lymphoma (PMBL), and post-transplant lymphoproliferative disorders (PTLD). We believe that BV could potentially provide a strong additional treatment option for patients suffering from NHL. OBJECTIVE Perform a systematic review on the use of BV in non-Hodgkin lymphoma (NHL) and other CD30+ malignancies in humans. DATA SOURCES We searched various databases including PubMed (1946-2015), EMBASE (1947-2015), and Cochrane Central Register of Controlled Trials (1898-2015). ELIGIBILITY CRITERIA Inclusion criteria specified all studies and case reports of NHLs in which BV therapy was administered. INCLUDED STUDIES A total of 28 articles met these criteria and are summarized in this manuscript. CONCLUSION Our findings indicate that BV induces a variety of responses, largely positive in nature and variable between NHL subtypes. With additional, properly powered prospective studies, BV may prove to be a strong candidate in the treatment of various CD30+ malignancies.

Economic evaluation for the UK of nab-paclitaxel plus gemcitabine in the treatment of metastatic pancreas cancer.

Acute graft-versus-host-disease (aGVHD) is a frequent and often lethal complication of allogeneic hematopoietic stem cell transplant despite prophylaxis. Tocilizumab is a humanized anti-IL-6 receptor monoclonal antibody that has evidence of activity in patients with steroid refractory (SR) GVHD. We retrospectively report on nine patients with grade 3 or 4 SR aGVHD who received tocilizumab. Eight mg/kg of tocilizumab was administered intravenously every 3–4 weeks. aGVHD grading and responses were based on consensus criteria. Median age at transplant was 48 years. Five patients had alternate donor sources. Median time from aGVHD onset to tocilizumab administration was 44 days. Two patients had complete responses and two had partial responses. Median survival from start of tocilizumab was 26 days (range 13–1054). Our limited experience demonstrated an overall response rate of 44% (CR + PR); however, this response was not durable. Further studies are needed to determine the optimal time for tocilizumab initiation.

Silybum marianum (milk thistle) in the management and prevention of hepatotoxicity in a patient undergoing reinduction therapy for acute myelogenous leukemia

Background:The combination of nab-paclitaxel plus gemcitabine (NAB-P+GEM) has shown superior efficacy over GEM monotherapy in metastatic pancreas cancer (MPC). Independent cost-effectiveness/utility analyses of NAB-P+GEM from the payer perspective have not been conducted for the UK.Methods:A Markov model simulating the health outcomes and total costs was developed to estimate the life years gained (LYG) and quality-adjusted life years gained (QALY) and incremental cost-effectiveness (ICER) and cost-utility ratios (ICUR) for patients with MPC in a base case and in a probabilistic (PSA) sensitivity analysis. Total cost included the cost of supportive care medications, administration, chemotherapy, disease monitoring, and adverse reactions; and was discounted at 3.5% per year. A full lifetime horizon and third party payer perspective was chosen.Results:The total cost of NAB-P+GEM was £5466 higher than the cost for GEM. Respectively, LYGs were 0.97 vs 0.79 and QALYs were 0.52 vs 0.45, with ICER of £30 367/LYG and ICUR of £78 086/QALY, confirmed by PSA.Conclusions:The superior survival efficacy of NAB-P+GEM over GEM in the management of MPC is associated with positive cost-effectiveness and cost-utility.