Drug-drug interactions in subjects enrolled in SWOG trials of oral chemotherapy.

BACKGROUND: Patients with cancer are at increased risk of drug-drug interactions (DDI), which can increase treatment toxicity or decrease efficacy. It is especially important to thoroughly screen DDI in oncology clinical trial subjects to ensure trial subject safety and data accuracy. This study determined the prevalence of potential DDI involving oral anti-cancer trial agents in subjects enrolled in two SWOG clinical trials. METHODS: Completed SWOG clinical trials of commercially available agents with possible DDI that had complete concomitant medication information available at enrollment were included. Screening for DDI was conducted through three methods: protocol-guided screening, Lexicomp® screening, and pharmacist determination of clinical relevance. Descriptive statistics were calculated. RESULTS: SWOG trials S0711 (dasatinib, n = 83) and S0528 (everolimus/lapatinib, n = 84) were included. Subjects received an average of 6.6 medications (standard deviation = 4.9, range 0-29) at enrollment. Based on the clinical trial protocols, at enrollment 18.6% (31/167) of subjects had a DDI and 12.0% (20/167) had a DDI that violated a protocol exclusion criterion. According to Lexicomp®, 28.7% of subjects (48/167) had a DDI classified as moderate or worse, whereas pharmacist review indicated that 7.2% of subjects (12/167) had a clinically relevant interaction. The majority of clinically relevant DDI identified were due to the coadministration of acid suppression therapies with dasatinib (83.3%, 10/12). CONCLUSIONS: The high DDI prevalence in subjects enrolled on SWOG clinical trials, including a high prevalence that violate trial exclusion criteria, support the need for improved processes for DDI screening to ensure trial subject safety and trial data accuracy.

Outcome Assessments and Cost Avoidance of an Oral Chemotherapy Management Clinic.

BACKGROUND: Increasing use of oral chemotherapy drugs increases the challenges for drug and patient management. An oral chemotherapy management clinic was developed to provide patients with oral chemotherapy management, concurrent medication (CM) education, and symptom management services. This evaluation aims to measure the need and effectiveness of this practice model due to scarce published data. METHODS: This is a case series report of all patients referred to the oral chemotherapy management clinic. Data collected included patient demographics, depression scores, CMs, and types of intervention, including detection and management outcomes collected at baseline, 3-day, 7-day, and 3-month follow-ups. Persistence rate was monitored. Secondary analysis assessed potential cost avoidance. RESULTS: A total of 86 evaluated patients (32 men and 54 women, mean age of 63.4 years) did not show a high risk for medication nonadherence. The 3 most common cancer diagnoses were rectal, pancreatic, and breast, with capecitabine most prescribed. Patients had an average of 13.7 CMs. A total of 125 interventions (detection and management of adverse drug event detection, compliance, drug interactions, medication error, and symptom management) occurred in 201 visits, with more than 75% of interventions occurring within the first 14 days. A persistence rate was observed in 78% of 41 evaluable patients. The total estimated annual cost avoidance per 1.0 full time employee (FTE) was $125,761.93. CONCLUSIONS: This evaluation demonstrated the need for additional support for patients receiving oral chemotherapy within standard of care medical service. A comprehensive oral chemotherapy management referral service can optimize patient care delivery via early interventions for adverse drug events, drug interactions, and medication errors up to 3 months after initiation of treatment.

Gaps in Patient Education on Safe Handling and Disposal of Oral Chemotherapy Drugs: A Pilot Prospective Cohort Survey Study.

Background: Oral anticancer chemotherapy (OC) has been misperceived as being safer than intravenous chemotherapy, leading to its increased risk of improper handling and disposal. This survey study assessed the knowledge, practices and attitudes of pharmacists and patients regarding OC handling and disposal, gaps in knowledge and barriers to patient education. Methods: Surveys were developed based on literature review and pilot study validation results. Patients completed a 33-item paper or electronic survey whereas pharmacists completed a 38-item electronic survey. Descriptive statistics and Fisher's exact test computed using the R Project were used for analyses. Results: Pharmacist group (16/25, 62.5%) and patient group (14/29, 48.3%) believed that the oral route is safer than IV. Average overall correct response rates for pharmacist and patient groups were 78.3% and 61.9%, respectively. Significant gaps in knowledge between groups were observed in three sections (p < 0.05). Common barriers to providing patient education were insufficient training (70.8%) and insufficient time (50%). Conclusion: Pharmacist and patient knowledge, awareness and practices of OC safe handling and disposal are suboptimal. Areas of knowledge gaps and barriers to patient education were identified. Enhanced supports are needed to empower pharmacists to assume an active role in patient education on safe handling and disposal of OC.

Positive Patient Postoperative Outcomes with Pharmacotherapy: A Narrative Review including Perioperative-Specialty Pharmacist Interviews.

The influence of pharmacotherapy regimens on surgical patient outcomes is increasingly appreciated in the era of enhanced recovery protocols and institutional focus on reducing postoperative complications. Specifics related to medication selection, dosing, frequency of administration, and duration of therapy are evolving to optimize pharmacotherapeutic regimens for many enhanced recovery protocolized elements. This review provides a summary of recent pharmacotherapeutic strategies, including those configured within electronic health record (EHR) applications and functionalities, that are associated with the minimization of the frequency and severity of postoperative complications (POCs), shortened hospital length of stay (LOS), reduced readmission rates, and cost or revenue impacts. Further, it will highlight preventive pharmacotherapy regimens that are correlated with improved patient preparation, especially those related to surgical site infection (SSI), venous thromboembolism (VTE), nausea and vomiting (PONV), postoperative ileus (POI), and emergence delirium (PoD) as well as less commonly encountered POCs such as acute kidney injury (AKI) and atrial fibrillation (AF). The importance of interprofessional collaboration in all periprocedural phases, focusing on medication management through shared responsibilities for drug therapy outcomes, will be emphasized. Finally, examples of collaborative care through shared mental models of drug stewardship and non-medical practice agreements to improve operative throughput, reduce operative stress, and increase patient satisfaction are illustrated.

Use of tyrosine kinase inhibitors for chronic myeloid leukemia: management of patients and practical applications for pharmacy practitioners.

OBJECTIVE: To summarize the use of tyrosine kinase inhibitors (TKIs) for treatment of patients with chronic myeloid leukemia (CML) and provide practical information for patient management. DATA SOURCES: Literature was retrieved from PubMed (2000-January 2011), using the search terms chronic myeloid leukemia and tyrosine kinase inhibitor. Abstracts presented at the 2008-2010 annual meetings of the American Society of Hematology and the American Society of Clinical Oncology, reference citations from identified publications, as well as the manufacturers' full prescribing information for cited drugs, also were reviewed. STUDY SELECTION AND DATA EXTRACTION: Articles evaluating the efficacy and safety of the TKIs imatinib, nilotinib, and dasatinib were evaluated. Focus was placed on publications supporting management of patients with CML in the chronic phase. Reports presenting clinical trial information of TKIs in development also were included. DATA SYNTHESIS: The discovery of targeted tyrosine kinase inhibition of BCR-ABL kinase dramatically changed the treatment of CML. Imatinib, the first TKI approved for treatment of patients with Philadelphia chromosome--positive CML, demonstrated significant superiority over the previous standard of care: interferon plus cytarabine. The newer, more potent TKIs, nilotinib and dasatinib, have demonstrated improved efficacy over imatinib as first-line therapy and provide an effective option for patients with resistance or intolerance to imatinib. CONCLUSIONS: To maximize efficacy of TKI therapy, close patient management, involving frequent monitoring of patient response, is essential. Given the importance of continuing TKI therapy, early recognition and management of adverse events are critical to optimizing outcomes in patients with CML. In addition to the safety profile and considerations of comorbidities, additional factors can affect therapeutic selection, including drug-drug and drug-food interactions. Research investigating new therapies, particularly for patients harboring the T315I mutation-which remains refractory to current TKIs-continues in the quest to improve outcomes in patients with CML.

Improvement Initiative to Develop and Implement a Tool for Detecting Drug-Drug Interactions During Oncology Clinical Trial Enrollment Eligibility Screening.

OBJECTIVES: Screening subjects for drug-drug interactions (DDIs) before enrollment in oncology clinical trials is integral to ensuring safety, but standard procedures or tools are not readily available to screen DDI in this setting. Our objectives were to develop a DDI screening tool for use during oncology clinical trial enrollment and to test usability in single-center and multicenter pilot studies. METHODS: A multistage approach was used for this quality improvement intervention. Semistructured interviews with individuals responsible for DDI screening were conducted to develop a prototype tool. The tool was used for screening DDI in subjects enrolling in National Clinical Trials Network trials of commercially available agents during a single-center 3-month pilot. Improvements were made, and a 3-month multicenter pilot was conducted at volunteer SWOG Cancer Research Network sites. Participants were surveyed to determine tool usability and efficiency. RESULTS: A tool was developed from semistructured interviews. A critical feature was reporting which medications had specific pharmacokinetic and pharmacodynamic characteristics including transporter and cytochrome P450 substrates, inhibitors, or inducers and QT prolongation. In the 12-site study, average (SD) DDI screening time for each patient decreased by 15.7 (10.2) minutes (range, 3-35 minutes; P < 0.001). Users reported the tool highly usable, with >90% agreeing with all positive usability characterizations and disagreeing with all negative complexity characterizations. CONCLUSIONS: A DDI screening tool for oncology clinical trial enrollment was created and its usability confirmed. Further testing with more diverse investigator sites and study drugs during eligibility screening is warranted to improve safety and data accuracy within clinical trials.

Challenges to Implementation of the Co-Curriculum in Accredited Pharmacy Programs.

Objective. To determine areas of concern, and challenges to implementing and assessing the co-curriculum in accredited Doctor of Pharmacy programs, along with how confident programs are in their ability to meet the co-curriculum requirement as mandated by the Accreditation Council for Pharmacy Education (ACPE).Methods. A survey was administered to all ACPE-accredited pharmacy programs to collect information regarding areas of concern, challenges, and confidence in their ability to meet the co-curriculum requirement. The frequency of responses to items are presented along with comparisons based on characteristics, including institution type, cohort size, most recent ACPE accreditation review, and supporting offices.Results. The most common concerns centered on the documentation and assessment process. The most commonly reported challenges were lack of enthusiasm or buy-in from faculty, staff, and students; lack of a clear definition of co-curriculum; and faculty time and insufficient staff. Overall, programs had a high level of confidence in their ability to meet the requirements for co-curriculum. The only differences found were related to supporting offices and cohort size.Conclusion. The results suggest that having supporting offices may reduce the co-curriculum burden. Similarly, student cohort size may have an impact on the challenges for some programs, particularly those with moderate-sized cohorts reporting challenges related to faculty and staff. Further research is needed to determine how programs address these critical issues, and to explore whether programs report differently on these areas after completing an accreditation review. The study results may be useful to members of the Academy when evaluating co-curriculum.

A prospective crossover pilot study to evaluate the use of a topical wound gel in patients with cutaneous toxicity caused by epidermal growth factor receptor inhibitors.

One of the dose-limiting toxicities of epidermal growth factor receptor inhibitors (EGFRIs) is a papulopustular rash that is often pruritic and painful. Secondary skin infection can occur from scratching to relieve the pruritus. Studies suggest that this rash might be a surrogate marker for efficacy; therefore, effective rash management is needed to allow patients to use EGFRIs without unnecessary dose modifications. In this single-center, prospective, crossover study, we evaluated the use of a topical gel (Regenecare Wound Gel) for relieving the pruritus and pain of EGFRI-induced rash among oncology patients. The secondary end points were patient satisfaction, adverse effects, and EGFRI dose modifications. At the occurrence of grade 2 skin rash, patients started applying the study gel to the right side of their face; after 1 week, they began applying it to both sides of their face for up to an additional 5 weeks. Each week, providers performed a facial evaluation and patients rated their symptoms and satisfaction on questionnaires. Of the 20 patients enrolled, 13 were evaluable. Reduction in itch at the end of week 1 was greater on the right (treated) side in 69% of patients greater on the left (untreated) side in 8%, and the same in 23% (P = 0.01). The pattern was similar for pain, but the differences were not significant. On average, patients rated the gel as being moderately to extremely effective for alleviating symptoms, improving rash appearance, and promoting healing and found it easy to apply. No adverse effects were documented. Four patients (31%) required EGFRI dose modifications because of rash. Taken together, these findings suggest that the topical wound gel is effective in relieving rash-associated itching in patients receiving EGFRIs and is associated with high patient satisfaction.

Co-Curriculum Implementation and Assessment in Accredited Doctor of Pharmacy Programs.

Objective. To determine how accredited Doctor of Pharmacy programs implement and evaluate the co-curriculum requirement as mandated by the Accreditation Council for Pharmacy Education (ACPE). Methods. A survey was administered to all ACPE-accredited pharmacy programs to collect information regarding how co-curriculum models were being implemented, including types of activities, structure, learning outcomes, oversight, and assessment. The frequency of responses to items were presented to describe the general features of co-curriculum models. Results. The types of co-curricular activities reported by programs were generally consistent, with the majority of programs categorizing these activities and allowing students to choose which they would engage in. Most respondents reported that the program mapped co-curricular activities to learning outcomes, primarily ACPE Standards 1-4. The structural oversight of the co-curriculum typically included a co-curriculum committee, subcommittee, or task force, and supporting offices. The most common offices/departments involved in the co-curriculum were assessment, student affairs/services, experiential education, and academic/curricular affairs. The most common assessments were reflections, self-assessment surveys, and checklists. Conclusion. In most programs, implementation of the co-curriculum was a joint effort among various individuals, committees, and offices. Given the developing nature of programs, descriptive studies should be repeated to identify how programs develop and enhance co-curriculum models. The study results may be useful to members of the Academy when evaluating the current state of co-curriculum implementation and potential areas for program development.

A prospective study to validate the functional assessment of cancer therapy (FACT) for epidermal growth factor receptor inhibitor (EGFRI)-induced dermatologic toxicities FACT-EGFRI 18 questionnaire: SWOG S1013.

BACKGROUND: Papulopustular rash is a common class effect of epidermal growth factor receptor inhibitors (EGFRI) that can affect patients' health-related quality of life and cause disruptions to treatment. SWOG S1013 (NCT01416688) is a multi-center study designed to validate the Functional Assessment of Cancer Therapy EGFRI 18 (FACT-EGFRI 18) using 7-items from the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 to assess EGFRI-induced skin-related toxicities and their impact on functional status. METHODS: Patients with a diagnosis of colorectal or lung cancer to receive EGFRI therapies for at least 6 weeks were enrolled. Patient self-assessments using the FACT-EGFRI 18 were completed prior to undergoing CTCAE assessment by trained clinicians at baseline, weekly × 6, and then monthly × 3. The psychometric properties of the FACT-EGFRI 14 (skin toxicity items only) and 18 (plus 2 nail and 2 hair items) were established based on criterion validity, known groups validity, internal consistency reliability, and responsiveness to change. RESULTS: Of the 146 registered patients, 124 were evaluable. High Cronbach's alpha (> 0.70) for both FACT-EGFRI 14 and FACT-EGFRI 18 scores across assessment times were observed. Although agreement (i.e. criterion validity) between individual and summary scales of the FACT-EGFRI 18 for assessing skin toxicity was good, agreement with the clinician-reported CTCAE was only fair. The minimal important difference was determined to be 3 points. The results also demonstrated responsiveness to symptom change. DISCUSSION: Based on the results of this multi-center validation study, the FACT-EGFRI 18 patient-reported outcome instrument provided data from the patient's perspective yielding unique information as well as complementing clinician-rated CTCAE grades, especially for the symptoms of pain, pruritus, and paronychia. CONCLUSIONS: Good to excellent psychometric properties for the FACT-EGFRI 18 were demonstrated, supporting further use of this patient-reported outcomes measure. Additional validation with a more diverse group of patients should be conducted.

Zoledronic acid markedly improves bone mineral density for patients with monoclonal gammopathy of undetermined significance and bone loss.

PURPOSE: Patients with monoclonal gammopathy of undetermined significance (MGUS) have increased rates of bone resorption, osteopenia, osteoporosis, and risk of fractures. This study was undertaken to determine the efficacy and safety of zoledronic acid for patients with MGUS and enhanced bone loss. EXPERIMENTAL DESIGN: In this phase II open-label study, 54 patients with MGUS and osteopenia or osteoporosis were administered zoledronic acid 4 mg i.v. at 0, 6, and 12 months. The primary efficacy end point was bone mineral density, assessed using a dual-energy X-ray absorptiometry scan in the lumbar (L)-spine done at screening and at 13 months (1 month after the final zoledronic acid infusion). RESULTS: At study end for all patients (N = 54), L-spine T-scores improved by a median of +0.27 (range, -0.38 to +3.91), corresponding to a median increase in bone mineral density of +15.0% (range, -18.0% to +1,140.0%; P < 0.0001). Hip T-scores improved by a median of +0.10 (range, -2.40 to +2.03), corresponding to a median increase of +6.0% (range, -350.0% to +165.0%). During the study, no new fractures, osteonecrosis of the jaw, or significant renal adverse events were reported. CONCLUSIONS: Zoledronic acid administered i.v. at a dosage of 4 mg every 6 months for three doses total was well-tolerated and substantially improved bone mineral density for patients with MGUS and bone loss. Zoledronic acid may be effective for the prevention of new fractures in this high-risk population.

National Trends in the Adoption of Pharmacy Curriculum Outcomes Assessment for Student Assessment and Remediation.

Objective. To determine and describe the current uses of the Pharmacy Curriculum Outcomes Assessment (PCOA) by US schools and colleges of pharmacy. Methods. Assessment professionals from 135 US schools and colleges of pharmacy were invited to complete a 38-item electronic survey. Survey items were designed to investigate common uses of the PCOA, cut points, and "stakes" assigned to the PCOA, identification of at-risk students, and remediation approaches. Results. The school response rate was 68%. The most common uses of the PCOA included curricular assessment (76%), individual student performance assessment (74%), and cohort performance assessment (71%). The PCOA was most frequently administered to third-year pharmacy (P3) students. The approach for assigning "stakes" to PCOA performance varied among programs depending on the student's professional year in the curriculum. Programs used a variety of approaches to establish the benchmark (or cut point) for PCOA performance. Remediation for at risk students was required by less than 25% of programs. Remediation was most commonly required for P3 students (22%). Conclusion. Survey results indicate wide variability between programs regarding PCOA cut points (benchmarks), stakes, and remediation approaches. In the future, it will be important for pharmacy educators to identify and study best practices for use of PCOA within student assessment and remediation plans.

Drug interaction screening in SWOG clinical trials.

PURPOSE: The frequency and process for drug interaction (DI) screening at sites enrolling patients into SWOG clinical trials were studied. METHODS: Survey invitations were e-mailed to 180 SWOG head clinical research associates to determine the frequency of and personnel involved in DI assessment in subjects who were screened for and enrolled in clinical trials at their sites. Descriptive statistics were performed to evaluate the data. RESULTS: A total of 83 surveys recorded a response to at least 1 question, yielding an overall response rate of 46.1%. At least 72 completed surveys were submitted, for a completion rate of 40.0%. The majority of sites (51%) reported that DI screening only occurred during eligibility assessment when a DI was included in the protocol exclusion criteria. The pharmacist was "always" involved in DI screening during eligibility assessment at 17% of sites. Clinical research coordinators (56%) and research nurses (45%) were the predominant personnel who performed DI screening to assess eligibility for trial enrollment. A subset of sites (3-6%) reported not having access to a pharmacist. Fewer than 10% of sites reported that they "always" use drug information services, websites, resources, or literature searches, though many tools were used "often" or "sometimes" by more than 20% of sites. CONCLUSION: A survey revealed that DI screening was not being systematically conducted within SWOG clinical trials. When DI screening did occur, it was primarily conducted by clinical research coordinators or study nurses. Pharmacist-led DI screening was not the current practice within SWOG sites surveyed and was precluded by a lack of pharmacists' availability or involvement.

In vitro and ex-vivo evaluation of topical formulations designed to minimize transdermal absorption of Vitamin K1.

Topical application of Vitamin K1 has been demonstrated to effectively treat papulopustular skin rash, a serious and frequently encountered side effect of Epidermal Growth Factor Inhibitors (EGFRIs). Systemic absorption of vitamin K1 from skin and the resultant consequence of antagonizing EGFRIs anticancer effects jeopardizes the clinical acceptability of this rather effective treatment. The purpose of the present study was to rationally formulate and evaluate the release rate and transdermal absorption of a wide range of Vitamin K1 dermal preparations with a variety of physiochemical properties. A library of 33 formulations with were compounded and tested for Vitamin K1 permeation using hydrophobic membranes and porcine skin mounted in a Fran diffusion cells. Our results demonstrate the lowest diffusion for water-in-oil emulsions, which also demonstrated a negligible transdermal absorption. The statistical analysis showed a significant correlation between in vitro and ex vivo results. While viscosity did not have a significant impact on the diffusion or absorption of vitamin K1, an increase in the lipid content was correlated with an increase in transmembrane diffusion (not with transdermal absorption). Overall, formulation design significantly impacts the release rate and transdermal absorption of vitamin K1, and confirms the possibility of minimal systemic distribution of this vitamin for this specific purpose.

Two-Year Trends of Taxane-Induced Neuropathy in Women Enrolled in a Randomized Trial of Acetyl-L-Carnitine (SWOG S0715).

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a common and disabling side effect of taxanes. Acetyl-L-carnitine (ALC) was unexpectedly found to increase CIPN in a randomized trial. We investigated the long-term patterns of CIPN among patients in this trial. Methods: S0715 was a randomized, double-blind, multicenter trial comparing ALC (1000 mg three times a day) with placebo for 24 weeks in women undergoing adjuvant taxane-based chemotherapy for breast cancer. CIPN was measured by the 11-item neurotoxicity (NTX) component of the FACT-Taxane scale at weeks 12, 24, 36, 52, and 104. We examined NTX scores over two years using linear mixed models for longitudinal data. Individual time points were examined using linear regression. Regression analyses included stratification factors and the baseline score as covariates. All statistical tests were two-sided. Results: Four-hundred nine subjects were eligible for evaluation. Patients receiving ALC had a statistically significantly (P = .01) greater reduction in NTX scores (worse CIPN) of -1.39 points (95% confidence interval [CI] = -2.48 to -0.30) than the placebo group. These differences were particularly evident at weeks 24 (-1.68, 95% CI = -3.02 to -0.33), 36 (-1.37, 95% CI = -2.69 to -0.04), and 52 (-1.83, 95% CI = -3.35 to -0.32). At 104 weeks, 39.5% on the ALC arm and 34.4% on the placebo arm reported a five-point (10%) decrease from baseline. For both treatment groups, 104-week NTX scores were statistically significantly different compared with baseline (P < .001). Conclusions: For both groups, NTX scores were reduced from baseline and remained persistently low. Twenty-four weeks of ALC therapy resulted in statistically significantly worse CIPN over two years. Understanding the mechanism of this persistent effect may inform prevention and treatment strategies. Until then, the potential efficacy and harms of commonly used supplements should be rigorously studied.

Cetuximab: an epidermal growth factor receptor monoclonal antibody for the treatment of colorectal cancer.

BACKGROUND: Cetuximab is a recombinant human/mouse chimeric epidermal growth factor receptor (EGFR) monoclonal antibody. It was approved by the US Food and Drug Administration in February 2004 to be used in combination with irinotecan for the treatment of EGFR-expressing, metastatic colorectal cancer in patients who had failed to improve with irinotecan-based chemotherapy. Cetuximab was also approved for administration as a single agent in the treatment of patients with EGFR-expressing, metastatic colorectal cancer who are intolerant to irinotecan-based chemotherapy. OBJECTIVE: This article reviews the role of cetuximab, an EGFR monoclonal antibody, in the treatment of colorectal cancer. METHODS: A MEDLINE search was conducted of articles published from 1976 to the present using the terms cetuximab, C225, IMC-C225, colon cancer, colorectal cancer, monoclonal therapy, and target therapy. Abstracts presented at the American Society of Clinical Oncology annual meetings from 2000 to 2004 and the 2004 Gastrointestinal Cancers Symposium were reviewed and included as applicable. RESULTS: In a Phase III trial, cetuximab was administered to 329 patients with colorectal cancer who were irinotecan refractory and/or had failed to respond to oxaliplatin treatment. Partial response was achieved in 10.8% of patients who received cetuximab monotherapy and 22.9% of patients who received cetuximab plus irinotecan therapy (P = 0.007). The overall response rate in 2 Phase II trials using the conventional dosing regimen of cetuximab to treat EGFR-expressing, metastatic colorectal cancer that was refractory to irinotecan therapy ranged from 9% to 12%. The drug was well tolerated with proper administration precautions. The most common adverse events reported included acnelike rash and hypersensitivity reaction. The positive correlation of the incidence of skin reactions to response rates and median survival is one aspect that warrants further investigation in terms of its use as a response predictor. Unfortunately, the role of immunohistochemistry for EGFR expression continues to be a poor predictor of patients who may benefit from cetuximab. Clinical studies are ongoing of cetuximab in combination with radiation therapy and/or platinum in patients with squamous cell head and neck cancer, as well as cetuximab in combination with various antineoplastic agents in the treatment of non-small cell lung cancer and pancreatic cancer. CONCLUSIONS: Cetuximab has shown considerable activity-both as monotherapy and in combination with chemotherapy-in the treatment of metastatic colorectal cancer that is resistant to chemotherapy. The future of cetuximab lies in its use in combination with antineoplastic agents and/or radiation therapy in the treatment of colorectal cancer, head and neck cancer, non-small cell lung cancer, and pancreatic cancer. The lack of a predictive marker that would allow clinicians to select patients who are most likely to benefit from cetuximab therapy, especially taking into consideration the high costs of this medication, remains a challenge.

Potential drug-drug interaction between interferon alfa-2b and gemfibrozil in a patient with malignant melanoma.

BACKGROUND: In the United States, patients with high-risk stage II or III melanoma are often treated with adjuvant interferon (IFN) therapy for 1 year after surgery. Adverse events associated with IFN alfa-2b use are primarily constitutional symptoms. However, hypertriglyceridemia requiring treatment has been reported. OBJECTIVE: The aim of this report was to describe a potential drug-drug interaction between IFN alfa-2b and gemfibrozil in a patient with malignant melanoma. The possible mechanism of this potential interaction was examined. METHODS: This report presents the case of a 43-year-old male patient weighing 101 kg with newly diagnosed stage III melanoma of the left arm, with metastasis to the supraclavicular node. The patient presented to the University of California Irvine Medical Center, Orange, California with severe gastrointestinal (GI) symptoms and elevated hepatic enzyme concentrations at week 48 of 104 of adjuvant treatment of malignant melanoma (IFN alfa 11 MU SC TIW in combination with the investigational melanoma vaccine melanoma theraccine 1.25 mL [I mL lysate + 0.25 mL vaccine adjuvant] given SC at weeks 1, 2, 3, 4, 8, 16, 24, 32, 40, and 48 and then every 8 weeks until week 104), and IFN-induced hypertriglyceridemia (gemfibrozil 600 mg PO BID). The patient had no history of cardiovascular or GI disease and was not receiving any concomitant medication. The possible mechanism of this potential IFN alfa-gemfibrozil interaction as related to the cytochrome P450 (CYP) enzyme system was assessed. RESULTS: In this case of a possible drug-drug interaction between IFN alfa 11 MU TIW and gemfibrozil 600 mg BID in a patient undergoing treatment for IFN-induced hypertriglyceridemia, the Naranjo Adverse Drug Reactions (ADR) Probability Scale score was 7 (ie, ADR possibly related to treatment). CONCLUSIONS: Both IFN and gemfibrozil inhibit the activity of the hepatic enzymes CYP1A2 and CYP2C19. A possible drug-drug interaction between IFN alfa 11 MU TIW and gemfibrozil 600 mg BID was reported in a patient undergoing treatment for IFN-induced hypertriglyceridemia.

Effects of a formulary change from granulocyte colony-stimulating factor to granulocyte-macrophage colony-stimulating factor on outcomes in patients treated with myelosuppressive chemotherapy.

STUDY OBJECTIVE: To evaluate the effects on efficacy and safety of a formulary change from granulocyte colony-stimulating factor (G-CSF) to granulocyte-macrophage CSF (GM-CSF). DESIGN: Retrospective chart review. SETTING: Single-center academic institution. PATIENTS: Fifty-six patients aged 18 years or older with breast cancer, lung cancer, melanoma, Hodgkin's lymphoma, or non-Hodgkin's lymphoma who developed neutropenia within 4 weeks after treatment with myelosuppressive chemotherapy and who had been given five or more doses of CSF as primary or secondary prophylaxis from January 1995-March 2002. Twenty-nine patients treated before January 2000 were given G-CSF; after the formulary change in January 2000, 27 patients were primarily given GM-CSF. MEASUREMENTS AND MAIN RESULTS: The primary efficacy end point was time to an absolute neutrophil count of 1.5x10(3)/mm3 or greater after treatment with CSF. Second and third efficacy end points, respectively, were frequency of febrile neutropenia and effect of CSF treatment on schedule and dose intensity of subsequent chemotherapy cycles. Primary and secondary safety end points, respectively, were frequency of adverse events and use of resources used to manage these events. The time to neutrophil recovery was similar with G-CSF and GM-CSF. Febrile neutropenia was more common in the patients given GM-CSF. Chemotherapy dose delays also were more common in patients treated with GM-CSF, as was the frequency of fever. Use of resources (platelet and red blood cell transfusions, intravenous antibiotics, and hospitalizations) was greater in the patients treated with GM-CSF. CONCLUSION: The formulary change to GM-CSF was associated with a higher frequency of febrile neutropenia, resultant chemotherapy dose delays, more adverse events, and greater use of resources to manage the adverse events. These results suggest that G-CSF and GM-CSF are not therapeutically equivalent, with G-CSF having a superior safety and efficacy profile for the prevention of chemotherapy-induced neutropenic events.

Implementation and preliminary outcomes of a comprehensive oral chemotherapy management clinic.

PURPOSE: Improved outcomes achieved by an oral chemotherapy management (OCM) clinic, including a reduction in the need for medication-related interventions, are reported. SUMMARY: A retrospective observational cohort study was conducted to assess the effectiveness of an OCM clinic providing comprehensive medication therapy management (MTM) services, including education on various oral chemotherapy agents, concurrent medications, and symptom management, as well as insurance assistance. Patient demographics, self-rated depression scores, and data on concurrent medication use, types of interventions, and intervention outcomes were collected at baseline and at follow-up visits for up to three months. Thirty clinic patients (9 men and 21 women with a mean age of 64.5 years) were evaluated; the majority had advanced-stage cancer and no live-in caregiver. On average, the patients had 2.8 comorbid conditions, including hypertension (43%), chronic pain (43%), and diabetes (37%), and were taking 12.7 concurrent medications (range, 3-26). In general, OCM clinic interventions in five categories (adverse events, adherence, drug interactions, medication errors, and symptom management) decreased during the measured time periods. About 70% of OCM clinic interventions were associated with positive outcomes (i.e., complete resolution of event or improved response to therapy), with 67% and 36% of interventions resulting in potential cost avoidance and cost savings, respectively. Rates of optimal oral chemotherapy adherence and persistence were estimated at 70%. CONCLUSION: An OCM clinic with comprehensive MTM services was effective in delivering early interventions, resulting in decreased rates of adverse effects, nonadherence, drug interactions, and medication errors over time.

Randomized double-blind placebo-controlled trial of acetyl-L-carnitine for the prevention of taxane-induced neuropathy in women undergoing adjuvant breast cancer therapy.

PURPOSE: Chemotherapy-induced peripheral neuropathy (CIPN) is common and leads to suboptimal treatment. Acetyl-L-carnitine (ALC) is a natural compound involved in neuronal protection. Studies have suggested ALC may be effective for the prevention and treatment of CIPN. PATIENTS AND METHODS: A 24-week randomized double-blind trial comparing ALC (3,000 mg per day) with placebo in women undergoing adjuvant taxane-based chemotherapy was conducted. The primary objective was to determine if ALC prevents CIPN as measured by the 11-item neurotoxicity (NTX) component of the Functional Assessment of Cancer Therapy (FACT) -Taxane scale at 12 weeks. Secondary objectives included changes in 24-week end points, functional status (FACT-Trial Outcome Index [TOI]), fatigue (Functional Assessment of Chronic Illness Therapy [FACIT] -Fatigue), and NTX grade. RESULTS: A total of 409 patients were evaluable (208 received ALC; 201, placebo). In a multivariate linear regression, week-12 scores were 0.9 points lower (more CIPN) with ALC than placebo (95% CI, -2.2 to 0.4; P = .17), whereas week-24 scores were 1.8 points lower with ALC (95% CI, -3.2 to -0.4; P = .01). Patients receiving ALC were more likely to have a > 5-point decrease in FACT-NTX scores (38% v 28%; P = .05), and FACT-TOI scores were 3.5 points lower with ALC (P = .03). Grade 3 to 4 neurotoxicity was more frequent in the ALC arm (eight v one). No differences between arms were observed for FACIT-Fatigue or other toxicities. Serum carnitine level increased with ALC but remained stable with placebo. CONCLUSION: There was no evidence that ALC affected CIPN at 12 weeks; however, ALC significantly increased CIPN by 24 weeks. This is the first study to our knowledge showing that a nutritional supplement increased CIPN. Patients should be discouraged from using supplements without proven efficacy.