Trends in the delivery of care to oncology patients in the United States: Emphasis on the role pharmacists on the healthcare team.

OBJECTIVE: The purpose of this study was to identify trends in oncology care that allow one to forecast workforce supply and demand, the training and skills needed by the oncology pharmacist for the likely future of oncology care. METHODS: Interviews were conducted with experienced oncology pharmacists in leadership roles at 20 organizations balanced by geographic region and type of practice site (academic or community/ambulatory). Results were analyzed using descriptive statistics and theme identification. RESULTS: Practice sites differed widely in numbers of patient visits, practitioner/patient ratios, residency program presence, and other structural features. Despite this, the majority reported an expectation of growth in cancer patients, oncology physicians, oncology pharmacists, pharmacy technicians, oncology nurses, and advanced practice practitioners in the next two to five years. Fifty percent of sites currently support Post Graduate Year 2 (PGY2) oncology residencies. At least 50% reported routine pharmacist involvement in 12 clinical functions. More future involvement was predicted for immunotherapy (80%) and oral oncolytic therapy (90%). Interprofessional involvement was reported for a broad variety of practice-related committees and patient education teams. Limited pharmacist involvement in credentialing, quality measurement, and value-based reimbursement systems was found. CONCLUSION: Anticipated increases in demand for oncology pharmacists strongly suggest the need for more PGY2 oncology residency programs and on-the-job oncology training programs. Oncology pharmacists are currently involved in many clinical and administrative functions including multidisciplinary management. While a core set of clinical functions has been identified, oncology pharmacists must prepare for the increased use of oral oncology agents and immunotherapy. Pharmacist involvement in value-based reimbursement and other data-based quality outcome measurements should be increased to optimize involvement in team-based patient care.

Effects of the leucovorin shortage: Pilot study investigating cost, efficacy, and toxicity comparison of low fixed-dose versus body surface area-adjusted leucovorin dosing in patients with resectable colon or metastatic colorectal cancer.

Purpose As a result of the leucovorin shortage, we switched from BSA-adjusted to low fixed-dose leucovorin in patients with colon cancer receiving fluorouracil-containing therapy. Methods A retrospective, pilot study of adults receiving intravenous leucovorin as part of a fluorouracil-containing treatment was conducted including individuals with stage II or III colon or newly diagnosed metastatic colorectal cancer. One low fixed-dose (leucovorin 50 mg) patient was matched by the investigator to one BSA-adjusted (leucovorin 200-500 mg/m2/dose) patient on disease stage and age. The objectives were to compare cost of alternative dosing strategies as well as efficacy and adverse event rates. Only patients being treated in the first-line metastatic colorectal cancer setting were included in the efficacy analysis. Results Fifty-eight patients were included. Leucovorin cost was reduced by 7- to 14-fold, and we were able to conserve a total of 1580-3400 doses of leucovorin by changing to fixed-dose (estimated from 200 mg/m2 or 400 mg/m2 dosing strategies, respectively). No statistically significant differences in progression-free survival ( p = 0.254), overall survival ( p = 0.923), or complications resulted. Conclusion Our decision to reduce the dose of leucovorin allowed us to conserve supply and control cost. The small sample size did not allow us to detect differences in efficacy or adverse event rates, and thus a larger study would be required to confirm our findings that efficacy was not compromised nor adverse effects greater.

Comparison of enteral and parenteral methods of urine alkalinization in patients receiving high-dose methotrexate.

Purpose Hyperhydration and urinary alkalinization is implemented with all high-dose (HD)-methotrexate infusions to promote excretion and prevent precipitation of methotrexate in the renal tubules. Our institution utilized enteral alkalinizing agents (sodium bicarbonate tablets and sodium citrate/citric acid solution) to alkalinize the urine of patients receiving HD-methotrexate during a parenteral sodium bicarbonate and sodium acetate shortage. The purpose of this study is to establish the safety and efficacy of the enteral route for urine alkalinization. Methods A single-center, retrospective, cohort study was conducted comparing cycles of HD-methotrexate using enteral alkalinizing agents to parenteral sodium bicarbonate. The primary objective was to compare the time, in hours, from administration of first inpatient administered dose of alkalinizing agent to time of achieving goal urine pH. Secondary objectives evaluated total dose of sodium bicarbonate required to achieve goal urine pH, time from start of urine alkalinizing agent until time of achieving methotrexate level safe for discharge, and toxicities associated with methotrexate and the alkalinizing agents. Results A total of 118 patients were included in this study, equally divided into two cohorts based on parenteral versus enteral routes of administration. No statistical difference was determined between the two cohorts regarding time to goal urine pH (6.5 h versus 7.9 h, P = 0.051) or regarding time to methotrexate level deemed safe for discharge (63.5 h versus 62.5 h, p = 0.835). There were no significant differences in methotrexate-induced toxicities. Conclusion Our study found enteral routes of urine alkalinization to be a viable alternative to the traditional parenteral sodium bicarbonate, especially during parenteral sodium bicarbonate and acetate shortages.

Timed sequential therapy for acute myelogenous leukemia: Results of a retrospective study of 301 patients and review of the literature.

Timed sequential therapy (TST) aims to improve outcomes in acute myelogenous leukemia (AML) by harnessing drug-induced cell cycle kinetics of AML, where a second drug is timed to coincide with peak leukemia proliferation induced by the first drugs. We analyzed outcomes in 301 newly diagnosed AML patients treated from 2004-2013 with cytarabine, anthracycline, and etoposide TST induction. Median age was 52 (range 20-74) and complete remission rate 68%. With median follow-up 5.8 years, 5-year DFS and overall survival (OS) were 37% (95% CI 31-45%) and 32% (95% CI 27-38%), respectively. In multivariate analysis, older age, unfavorable cytogenetics, and WBC≥50×109/L resulted in worse OS. Among patients not undergoing blood and marrow transplant, a propensity score analysis, which reduces imbalance in baseline characteristics, showed consolidation with TST compared with 1 or more cycles high-dose cytarabine trended toward lower DFS and post-remission survival with hazard ratio (HR) 1.9 (95% CI 0.9-4.0), and 1.6 (95% CI 0.7-3.6), respectively. Our results demonstrate the efficacy and feasibility of TST induction for newly diagnosed patients with AML, with results comparable to that seen in clinical trials with other TST therapies and 7+3.

Epidemiology, outcomes, and risk factors of invasive fungal infections in adult patients with acute myelogenous leukemia after induction chemotherapy.

This is a retrospective, single-center study of adult patients with newly diagnosed acute myelogenous leukemia (AML), who received intensive induction timed sequential chemotherapy from 1/2005 to 6/2010. Among 254 consecutive AML patients, 123 (48.4%) developed an invasive fungal infection (IFI): 14 (5.5%) patients with invasive candidiasis (IC) and 108 (42.5%) patients with invasive mould infections (IMI). Among 108 IMI identified, 4 (3.7%) were proven, 1 (0.9%) probable, and 103 (95.4%) were possible, using current definitions. Overall, 6-month mortality was 23.7% (27/114) and 20.6% (26/126) for patients with and without an IFI, respectively. Older age (≥50 years; hazard ratio [HR]: 2.5, P < 0.001), female gender (HR: 1.7, P = 0.006), and baseline renal and/or liver dysfunction (HR: 2.4, P < 0.001) were the strongest mortality predictors. We report relatively low rates of IC despite lack of routine primary antifungal prophylaxis, albeit associated with poor long-term survival. High rates of IMI, the vast majority with a possible diagnosis, were observed. Host-related variables (demographics and baseline organ dysfunction) were identified as the most significant risk factors for IFI and mortality predictors in this series.

Standard of care and novel treatments for chronic lymphocytic leukemia.

PURPOSE: The standard of care and novel treatments for chronic lymphocytic leukemia (CLL) are reviewed. SUMMARY: Recent advances in the treatment of CLL have dramatically changed the therapeutic landscape for both patients and health care professionals. The majority of conventional first-line therapies are noncurative and are only used to treat disease that is symptomatic or progressive and include chlorambucil, monotherapy with purine analogues, and combination chemotherapy. Immunotherapeutic agents such as rituximab and alemtuzumab may be indicated in select patient populations. However, because clinical trials have found that overall survival does not depend on the initial therapy, selection of first-line therapy should be based on patient-specific factors and the patient's goals for therapy with respect to response, survival, and symptom palliation. Progression-free survival time and time to treatment are critical endpoints for CLL treatment. An increasingly important endpoint is minimal residual disease (MRD), as it is considered to be the major cause of relapse in CLL. Finally, comparison of toxicities between different therapies is critical in CLL, as it is in other disease states. Several new agents are currently being evaluated for use in CLL, including alvocidib, oblimersen, and lumiliximab. CONCLUSION: Chemotherapy remains the mainstay of treatment for the majority of patients with CLL. The introduction of rituximab, alemtuzumab, and bendamustine has improved the current outlook for patients with CLL. As overall survival does not appear to depend on the initial therapy, treatment should be selected based on patient-specific factors and goals. Challenges in CLL include determining when to initiate therapy, eradicating MRD, and managing therapeutic resistance.

NCCN Task Force Report: Specialty Pharmacy.

The use of specialty pharmacies is expanding in oncology pharmacy practice. Specialty pharmacies provide a channel for distributing drugs that, from the payor perspective, creates economies of scale and streamlines the delivery of expensive drugs. Proposed goals of specialty pharmacy include optimization of pharmaceutical care outcomes through ensuring appropriate medication use and maximizing adherence, and optimization of economic outcomes through avoiding unwarranted drug expenditure. In oncology practice, specialty pharmacies have become a distribution channel for various agents. The use of a specialty pharmacy, and the addition of the pharmacist from the specialty pharmacy to the health care team, may not only provide benefits for care but also present challenges in oncology practice. The NCCN Specialty Pharmacy Task Force met to identify and examine the impact of specialty pharmacy practice on the care of people with cancer, and to provide recommendations regarding issues discussed. This report provides recommendations within the following categories: education and training of specialty pharmacy practitioners who care for individuals with cancer, coordination of care, and patient safety. Areas for further evaluation are also identified.

Clinical activity of sequential flavopiridol, cytosine arabinoside, and mitoxantrone for adults with newly diagnosed, poor-risk acute myelogenous leukemia.

Flavopiridol, a cyclin-dependent kinase inhibitor, is cytotoxic to leukemic blasts. In a Phase II study, flavopiridol 50 mg/m(2) was given by 1-h infusion daily x 3 beginning day 1 followed by 2 g/m(2)/72 h ara-C beginning day 6 and 40 mg/m(2) mitoxantrone on day 9 (FLAM) to 45 adults with newly diagnosed acute myelogenous leukemia (AML) with multiple poor-risk features. Thirty patients (67%) achieved complete remission (CR) and 4 (9%) died. Twelve (40%) received myeloablative allogeneic bone marrow transplant (BMT) in first CR. Median OS and DFS are not reached (67% alive 12.5-31 months, 58% in CR 11.4-30 months), with median follow-up 22 months. Sixteen received FLAM in CR, with median OS and DFS 9 and 13.1 months, and 36% alive at 21-31 months. Short OS and DFS correlated with adverse cytogenetics, regardless of age or treatment in CR. The addition of allogeneic BMT in CR translates into long OS and DFS in the majority of eligible patients.

Characterization of the occurrence of ifosfamide-induced neurotoxicity with concomitant aprepitant.

PURPOSE: Ifosfamide is metabolized by the cytochrome P450 system to its active form, ifosforamide mustard. A potential side effect is neurotoxicity, often manifesting as confusion, hallucination, or seizure. Aprepitant, a neurokinin-1 inhibitor, is recommended for highly and moderately emetogenic chemotherapy regimens and may interfere with the metabolism of ifosfamide as it inhibits CYP3A4. The objective of the study is to identify if an increase in the incidence of neurotoxicity may be associated with the use of aprepitant with concomitant ifosfamide. METHODS: A retrospective study of inpatients with sarcoma who received a two or four-day regimen of MAI (mesna, doxorubicin, and ifosfamide) between January 1, 2004 and December 31, 2006 was conducted. Data collection focused on characterizing neurotoxicity of patients receiving ifosfamide with or without aprepitant. Correlation between serum creatinine, albumin, liver function tests, age, gender, and total doses of ifosfamide was examined. RESULTS: A total of 45 patients received ifosfamide of which 23 (51%) were male and 24 (53%) received aprepitant. All baseline characteristics were similar for those who received aprepitant versus those who did not. No significant differences were noted between patients with or without neurotoxicity for age, gender, or liver enzymes. Eight patients (18%) of 45 developed neurotoxicity of which six (75%) of those patients also received aprepitant. A trend of increased occurrence of neurotoxicity was noted with aprepitant administration (6 vs. 2 patients respectively, p = 0.176), although a statistical difference was not observed. A relative risk of 2.6 (95% CI, 0.47-26.6) was associated with the addition of aprepitant. CONCLUSIONS: An increased risk was identified for ifosfamide-induced neurotoxicity associated with aprepitant use; however, the observed difference was not statistically significant. The necessity of aprepitant given in association with ifosfamide may need to be reconsidered due to this risk.