Translation of Carbon-13 EPI for hyperpolarized MR molecular imaging of prostate and brain cancer patients.

PURPOSE: To develop and translate a metabolite-specific imaging sequence using a symmetric echo planar readout for clinical hyperpolarized (HP) Carbon-13 (13 C) applications. METHODS: Initial data were acquired from patients with prostate cancer (N = 3) and high-grade brain tumors (N = 3) on a 3T scanner. Samples of [1-13 C]pyruvate were polarized for at least 2 h using a 5T SPINlab system operating at 0.8 K. Following injection of the HP substrate, pyruvate, lactate, and bicarbonate (for brain studies) were sequentially excited with a singleband spectral-spatial RF pulse and signal was rapidly encoded with a single-shot echo planar readout on a slice-by-slice basis. Data were acquired dynamically with a temporal resolution of 2 s for prostate studies and 3 s for brain studies. RESULTS: High pyruvate signal was seen throughout the prostate and brain, with conversion to lactate being shown across studies, whereas bicarbonate production was also detected in the brain. No Nyquist ghost artifacts or obvious geometric distortion from the echo planar readout were observed. The average error in center frequency was 1.2 ± 17.0 and 4.5 ± 1.4 Hz for prostate and brain studies, respectively, below the threshold for spatial shift because of bulk off-resonance. CONCLUSION: This study demonstrated the feasibility of symmetric EPI to acquire HP 13 C metabolite maps in a clinical setting. As an advance over prior single-slice dynamic or single time point volumetric spectroscopic imaging approaches, this metabolite-specific EPI acquisition provided robust whole-organ coverage for brain and prostate studies while retaining high SNR, spatial resolution, and dynamic temporal resolution.

Development of a student-driven information technology support service.

BACKGROUND AND PURPOSE: To share our experience of a partnership created amongst students, staff, and faculty in order to address a gap in campus information technology (IT) customer services provided to students. EDUCATIONAL ACTIVITY AND SETTING: Student reliance on a complex educational technology ecosystem requires a robust IT infrastructure; however, campus IT services are often stretched in terms of their capacity to deliver immediate customer support. Compounding this problem is the inability of campus IT services to address issues arising from pharmacy education specific hardware or software. A student help desk (SHD), a student-initiated technology user group was developed. The support provided by the SHD covers student devices to the level of ensuring access to required curriculum technological resources. FINDINGS: Over 24 months, a total of 259 cases were addressed by the SHD. When examining the type of submissions, the top five requested categories included computer-based assessment, e-mail synchronization, curricular management software synchronization, wireless printing and encryption. These results suggest the perceived value and confidence by students and faculty in the service provided by the SHD. SUMMARY: The use of a SHD helped to resolve technology issues faced by students for curriculum engagement. Regardless of the challenges institutions may face in delivering their curriculum, students have the desire to be engaged in the governance of their curriculum. By creating a collaborative triad, this represents one example of how student motivation can be leveraged to conquer not just gaps in IT customer service, but potentially other programmatic issues within an institution.

Investigation of analysis methods for hyperpolarized 13C-pyruvate metabolic MRI in prostate cancer patients.

MRI using hyperpolarized (HP) carbon-13 pyruvate is being investigated in clinical trials to provide non-invasive measurements of metabolism for cancer and cardiac imaging. In this project, we applied HP [1-13 C]pyruvate dynamic MRI in prostate cancer to measure the conversion from pyruvate to lactate, which is expected to increase in aggressive cancers. The goal of this work was to develop and test analysis methods for improved quantification of this metabolic conversion. In this work, we compared specialized kinetic modeling methods to estimate the pyruvate-to-lactate conversion rate, kPL , as well as the lactate-to-pyruvate area-under-curve (AUC) ratio. The kinetic modeling included an "inputless" method requiring no assumptions regarding the input function, as well as a method incorporating bolus characteristics in the fitting. These were first evaluated with simulated data designed to match human prostate data, where we examined the expected sensitivity of metabolism quantification to variations in kPL , signal-to-noise ratio (SNR), bolus characteristics, relaxation rates, and B1 variability. They were then applied to 17 prostate cancer patient datasets. The simulations indicated that the inputless method with fixed relaxation rates provided high expected accuracy with no sensitivity to bolus characteristics. The AUC ratio showed an undesired strong sensitivity to bolus variations. Fitting the input function as well did not improve accuracy over the inputless method. In vivo results showed qualitatively accurate kPL maps with inputless fitting. The AUC ratio was sensitive to bolus delivery variations. Fitting with the input function showed high variability in parameter maps. Overall, we found the inputless kPL fitting method to be a simple, robust approach for quantification of metabolic conversion following HP [1-13 C]pyruvate injection in human prostate cancer studies. This study also provided initial ranges of HP [1-13 C]pyruvate parameters (SNR, kPL , bolus characteristics) in the human prostate.

Spatio-Temporally Constrained Reconstruction for Hyperpolarized Carbon-13 MRI Using Kinetic Models.

We present a method of generating spatial maps of kinetic parameters from dynamic sequences of images collected in hyperpolarized carbon-13 magnetic resonance imaging (MRI) experiments. The technique exploits spatial correlations in the dynamic traces via regularization in the space of parameter maps. Similar techniques have proven successful in other dynamic imaging problems, such as dynamic contrast enhanced MRI. In this paper, we apply these techniques for the first time to hyperpolarized MRI problems, which are particularly challenging due to limited signal-to-noise ratio (SNR). We formulate the reconstruction as an optimization problem and present an efficient iterative algorithm for solving it based on the alternation direction method of multipliers. We demonstrate that this technique improves the qualitative appearance of parameter maps estimated from low SNR dynamic image sequences, first in simulation then on a number of data sets collected in vivo. The improvement this method provides is particularly pronounced at low SNR levels.

Integration of a Community Pharmacy Simulation Program into a Therapeutics Course.

Objective. To demonstrate the feasibility of integrating the computer simulation, MyDispense, into a therapeutics course and to measure its effects on student perception and learning. Methods. We conducted a prospective study with an experimental phase and an implementation phase. In the first phase, students were randomized to complete a therapeutics case using MyDispense or traditional paper methods in class. In the second phase, all students completed two therapeutic cases using MyDispense in class with the option to complete four additional outside-of-class cases using MyDispense. Students completed pre- and post-tests in class and three surveys. Results. In the experimental phase, mean test scores increased from pre- to post-test for both MyDispense and traditional paper groups, but the difference between the groups was not statistically significant. Students in the traditional paper group reported statistically significant gains in confidence compared to the MyDispense group. In the implementation phase, mean test scores again increased, however, student perception of the use of MyDispense for therapeutics was negative. Completing the optional outside-of-class cases, however, was positively and significantly correlated with the midterm and final examination scores. Conclusion. Implementation of MyDispense in therapeutics may be feasible and has positive effects (eg, correlation with exam scores, capacity for immediate feedback, and potential for effective self-study). With short-term use and in the absence of assessment methods that also require seeking information from patients, students prefer to learn via traditional paper cases.

Technique development of 3D dynamic CS-EPSI for hyperpolarized 13 C pyruvate MR molecular imaging of human prostate cancer.

PURPOSE: The purpose of this study was to develop a new 3D dynamic carbon-13 compressed sensing echoplanar spectroscopic imaging (EPSI) MR sequence and test it in phantoms, animal models, and then in prostate cancer patients to image the metabolic conversion of hyperpolarized [1-13 C]pyruvate to [1-13 C]lactate with whole gland coverage at high spatial and temporal resolution. METHODS: A 3D dynamic compressed sensing (CS)-EPSI sequence with spectral-spatial excitation was designed to meet the required spatial coverage, time and spatial resolution, and RF limitations of the 3T MR scanner for its clinical translation for prostate cancer patient imaging. After phantom testing, animal studies were performed in rats and transgenic mice with prostate cancers. For patient studies, a GE SPINlab polarizer (GE Healthcare, Waukesha, WI) was used to produce hyperpolarized sterile GMP [1-13 C]pyruvate. 3D dynamic 13 C CS-EPSI data were acquired starting 5 s after injection throughout the gland with a spatial resolution of 0.5 cm3 , 18 time frames, 2-s temporal resolution, and 36 s total acquisition time. RESULTS: Through preclinical testing, the 3D CS-EPSI sequence developed in this project was shown to provide the desired spectral, temporal, and spatial 5D HP 13 C MR data. In human studies, the 3D dynamic HP CS-EPSI approach provided first-ever simultaneously volumetric and dynamic images of the LDH-catalyzed conversion of [1-13 C]pyruvate to [1-13 C]lactate in a biopsy-proven prostate cancer patient with full gland coverage. CONCLUSION: The results demonstrate the feasibility to characterize prostate cancer metabolism in animals, and now patients using this new 3D dynamic HP MR technique to measure kPL , the kinetic rate constant of [1-13 C]pyruvate to [1-13 C]lactate conversion.

Implementation of a virtual dispensing simulator to support US pharmacy education.

INTRODUCTION: A key element for pharmacy practice defined by the Accreditation Council for Pharmacy Education (ACPE) is medication use systems management. A web-based community pharmacy simulation originally created for Australian pharmacy students was adapted for pharmacy students in the United States (US). The objective of this study was to collaboratively adapt an existing international simulation program for utility in the US and measure student perceptions of a web-based community pharmacy simulation program in three US schools of pharmacy. METHODS: An Australian development team in collaboration with US pharmacy school faculty modified the existing MyDispense software to create a virtual environment that accurately represented US community pharmacy practice. Students at three US schools of pharmacy used the newly adapted version of MyDispense and were surveyed on their prior experience in community pharmacy and their perceptions of MyDispense as a learning tool. RESULTS: Overall 241 (44%) students completed the satisfaction survey. Approximately 40% of these students worked in a community pharmacy before starting pharmacy school. Most students agreed or strongly agreed that MyDispense was straightforward to learn (76%), was more realistic than addressing similar paper cases (73%), and offered a learning opportunity to safely make errors (84%). Qualitative thematic analysis revealed that MyDispense allowed students to practice how to gather patient information and ask appropriate questions, counsel patients, and practice the dispensing process. DISCUSSION AND CONCLUSIONS: Response to the US version of My Dispense is positive and proves to be a viable option for introducing and reinforcing community pharmacy practice skills to students during in their pharmacy education.

Assessing Prostate Cancer Aggressiveness with Hyperpolarized Dual-Agent 3D Dynamic Imaging of Metabolism and Perfusion.

New magnetic resonance (MR) molecular imaging techniques offer the potential for noninvasive, simultaneous quantification of metabolic and perfusion parameters in tumors. This study applied a three-dimensional dynamic dual-agent hyperpolarized 13C magnetic resonance spectroscopic imaging approach with 13C-pyruvate and 13C-urea to investigate differences in perfusion and metabolism between low- and high-grade tumors in the transgenic adenocarcinoma of mouse prostate (TRAMP) transgenic mouse model of prostate cancer. Dynamic MR data were corrected for T1 relaxation and RF excitation and modeled to provide quantitative measures of pyruvate to lactate flux (kPL ) and urea perfusion (urea AUC) that correlated with TRAMP tumor histologic grade. kPL values were relatively higher for high-grade TRAMP tumors. The increase in kPL flux correlated significantly with higher lactate dehydrogenase activity and mRNA expression of Ldha, Mct1, and Mct4 as well as with more proliferative disease. There was a significant reduction in perfusion in high-grade tumors that associated with increased hypoxia and mRNA expression of Hif1α and Vegf and increased ktrans , attributed to increased blood vessel permeability. In 90% of the high-grade TRAMP tumors, a mismatch in perfusion and metabolism measurements was observed, with low perfusion being associated with increased kPL This perfusion-metabolism mismatch was also associated with metastasis. The molecular imaging approach we developed could be translated to investigate these imaging biomarkers for their diagnostic and prognostic power in future prostate cancer clinical trials. Cancer Res; 77(12); 3207-16. ©2017 AACR.

The LGBTQI health forum: an innovative interprofessional initiative to support curriculum reform.

Lesbian, gay, bisexual, transgender, queer, and intersex (LGBTQI) individuals continue to face barriers to accessing appropriate and comprehensive healthcare. Compounding this problem, healthcare trainees report few training opportunities and low levels of preparedness to care for LGBTQI patients. In 2009, an interprofessional group of students and a faculty advisor at the University of California, San Francisco, developed a novel student-organized LGBTQI Health Forum for medical, dental, pharmacy, nursing, and physical therapy students to deliver LGBTQI health content that was otherwise absent from the formal curriculum. This elective course has evolved based upon participant feedback, emerging educational strategies, and the existing curricula infrastructure at our institution. After eight years of growth, this 10-contact hour weekend elective attracts over 250 participants each year. Plenary sessions deliver foundational terminology and skills to all attendees. Learners then select breakout sessions to attend, allowing for an individualized curriculum based upon specific interests and knowledge gaps. Breakout session topics prioritize traditionally underrepresented aspects of LGBTQI health in professional school curricula. This Forum serves as a model in which to supplement LGBTQI content into existing school curricula and offers an opportunity for interprofessional education. Next steps include conducting a formal evaluation of the curriculum, expanding our performance-based assessments, and potentially implementing a continuing education program for licensed practitioners. With a core group of interprofessional student organizers and a faculty champion, other institutions may view this course architecture as a potential way to offer learners not only LGBTQI content, but other underrepresented subjects into their own educational programs.

Metabolic imaging of patients with prostate cancer using hyperpolarized [1-¹³C]pyruvate.

This first-in-man imaging study evaluated the safety and feasibility of hyperpolarized [1-¹³C]pyruvate as an agent for noninvasively characterizing alterations in tumor metabolism for patients with prostate cancer. Imaging living systems with hyperpolarized agents can result in more than 10,000-fold enhancement in signal relative to conventional magnetic resonance (MR) imaging. When combined with the rapid acquisition of in vivo ¹³C MR data, it is possible to evaluate the distribution of agents such as [1-¹³C]pyruvate and its metabolic products lactate, alanine, and bicarbonate in a matter of seconds. Preclinical studies in cancer models have detected elevated levels of hyperpolarized [1-¹³C]lactate in tumor, with the ratio of [1-¹³C]lactate/[1-¹³C]pyruvate being increased in high-grade tumors and decreased after successful treatment. Translation of this technology into humans was achieved by modifying the instrument that generates the hyperpolarized agent, constructing specialized radio frequency coils to detect ¹³C nuclei, and developing new pulse sequences to efficiently capture the signal. The study population comprised patients with biopsy-proven prostate cancer, with 31 subjects being injected with hyperpolarized [1-¹³C]pyruvate. The median time to deliver the agent was 66 s, and uptake was observed about 20 s after injection. No dose-limiting toxicities were observed, and the highest dose (0.43 ml/kg of 230 mM agent) gave the best signal-to-noise ratio for hyperpolarized [1-¹³C]pyruvate. The results were extremely promising in not only confirming the safety of the agent but also showing elevated [1-¹³C]lactate/[1-¹³C]pyruvate in regions of biopsy-proven cancer. These findings will be valuable for noninvasive cancer diagnosis and treatment monitoring in future clinical trials.

Pharmacokinetics of penciclovir in healthy cats following oral administration of famciclovir or intravenous infusion of penciclovir.

OBJECTIVE: To investigate the pharmacokinetics of penciclovir in healthy cats following oral administration of famciclovir or IV infusion of penciclovir. ANIMALS: 6 cats. PROCEDURES: Cats received famciclovir (40 [n = 3] or 90 [3] mg/kg, PO, once) in a balanced crossover-design study; the alternate dose was administered after a ≥ 2-week washout period. After another washout period (≥ 4 weeks), cats received an IV infusion of penciclovir (10 mg/kg delivered over 1 hour). Plasma penciclovir concentrations were analyzed via liquid chromatography-mass spectrometry at fixed time points after drug administration. RESULTS: Mean ± SD maximum plasma concentration (C(max)) of penciclovir following oral administration of 40 and 90 mg of famciclovir/kg was 1.34 ± 0.33 µg/mL and 1.28 ± 0.42 µg/mL and occurred at 2.8 ± 1.8 hours and 3.0 ± 1.1 hours, respectively; penciclovir elimination half-life was 4.2 ± 0.6 hours and 4.8 ± 1.4 hours, respectively; and penciclovir bioavailability was 12.5 ± 3.0% and 7.0 ± 1.8%, respectively. Following IV infusion of penciclovir (10 mg/kg), mean ± SD penciclovir clearance, volume of distribution, and elimination half-life were 4.3 ± 0.8 mL/min/kg, 0.6 ± 0.1 L/kg, and 1.9 ± 0.4 hours, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Penciclovir pharmacokinetics following oral administration of famciclovir were nonlinear within the dosage range studied, likely because of saturation of famciclovir metabolism. Oral administration of famciclovir at 40 or 90 mg/kg produced similar C(max) and time to C(max) values. Therefore, the lower dose may have similar antiviral efficacy to that proven for the higher dose.

Prokinetic Therapy for Feed Intolerance in Critical Illness: One Drug or Two?

OBJECTIVE: To compare the efficacy of combination therapy, with erythromycin and metoclopramide, to erythromycin alone in the treatment of feed intolerance in critically ill patients. DESIGN: Randomized, controlled, double-blind trial. SETTING: Mixed medical and surgical intensive care unit. PATIENTS: Seventy-five mechanically ventilated, medical patients with feed intolerance (gastric residual volume ≥250 mL). INTERVENTIONS: Patients received either combination therapy (n = 37; 200 mg of intravenous erythromycin twice daily + 10 mg of intravenous metoclopramide four times daily) or erythromycin alone (n = 38; 200 mg of intravenous erythromycin twice daily) in a prospective, randomized fashion. Gastric feeding was re-commenced and 6-hourly gastric aspirates performed. Patients were studied for 7 days. Successful feeding was defined as a gastric residual volume <250 mL with the feeding rate ≥40 mL/hr, over 7 days. Secondary outcomes included daily caloric intake, vomiting, postpyloric feeding, length of stay, and mortality. MEASUREMENTS AND MAIN RESULTS: Demographic data; use of inotropes, opioids, or benzodiazepines; and pretreatment gastric residual volume were similar between the two groups. The gastric residual volume was significantly lower after 24 hrs of treatment with combination therapy, compared with erythromycin alone (136 ± 23 mL vs. 293 ± 45 mL, p = .04). Over the 7 days, patients treated with combination therapy had greater feeding success, received more daily calories, and had a lower requirement for postpyloric feeding, compared with erythromycin alone. Tachyphylaxis occurred in both groups but was less with combination therapy. Sedation, higher pretreatment gastric residual volume, and hypoalbuminemia were significantly associated with a poor response. There was no difference in the length of hospital stay or mortality rate between the groups. Watery diarrhea was more common with combination therapy (20 of 37 vs. 10 of 38, p = .01) but was not associated with enteric infections, including Clostridium difficile. CONCLUSIONS: In critically ill patients with feed intolerance, combination therapy with erythromycin and metoclopramide is more effective than erythromycin alone in improving the delivery of nasogastric nutrition and should be considered as the first-line treatment. ( Crit Care Med. 2007;35:2561-2567.) NQ Nguyen, M Chapman, RJ Fraser, LK Bryant, C Burgstad, RH Holloway.

Pancreatic enzyme pharmacotherapy.

Supplemental pancreatic enzyme preparations are provided to patients with conditions of pancreatic exocrine deficiency such as chronic pancreatitis and cystic fibrosis. These patients frequently experience steatorrhea, which occurs from inadequate fat absorption. The delivery of sufficient enzyme concentrations into the duodenal lumen simultaneously with meals can reduce nutrient malabsorption, improve the symptoms of steatorrhea, and in some cases alleviate the pain associated with chronic pancreatitis. Current clinical practices dictate administration of lipase 25,000-40,000 units/meal by using pH-sensitive pancrelipase microspheres, along with dosage increases, compliance checks, and differential diagnosis in cases of treatment failure. Despite the large number of specialty enzyme replacements available commercially, many patients remain dissatisfied with standard therapy, and future developments are needed to optimize treatment in these individuals.

A review of the relationship between parenteral nutrition and metabolic bone disease.

Metabolic bone disease (MBD) refers to the conditions that produce a diffuse decrease in bone density and strength because of an imbalance between bone resorption and bone formation. MBD can be a potential complication in patients receiving chronic parenteral nutrition (PN) therapy and the management of this condition presents a challenge for many clinicians. The etiology of PN-associated MBD is poorly understood, but traditional risk factors can include malnutrition, vitamin and mineral deficiencies, toxic contaminants in the PN solution, concomitant medications, and presence of certain disease states. Although additional studies are warranted to further elucidate the development and management of this condition, the following review discusses some of the important factors that may play a role in the genesis of PN-associated MBD and evaluates some potential strategies for the diagnosis and treatment of this complication.

Fentanyl HCl patient-controlled iontophoretic transdermal system for the management of acute postoperative pain.

OBJECTIVE: To summarize the pharmaceutics, pharmacokinetics, development, and clinical application of IONSYS, the fentanyl HCl patient-controlled iontophoretic transdermal system for the management of acute postoperative pain. DATA SOURCES: Clinical literature including both primary sources and review articles was accessed through a search of the MEDLINE databases (1980-October 2006). Key search terms included cutaneous analgesia, fentanyl, IONSYS, opioid, postoperative pain, and patient-controlled analgesia (PCA). Additional clinical trial and drug data were supplied by the manufacturer, the ALZA Corporation. STUDY SELECTION AND DATA EXTRACTION: Review articles, abstracts, and clinical studies related to patient-controlled iontophoretic transdermal fentanyl and postoperative pain management were analyzed. An evaluation of the research exploring IONSYS for the management of acute postoperative pain was conducted. Relevant information was then selected and is provided in this article. DATA SYNTHESIS: IONSYS is the first iontophoretic transdermal drug delivery system that utilizes low-level electrical energy to actively transport ionized fentanyl HCl through intact skin. Research has revealed that use of IONSYS for patients with acute postoperative pain is safe, effective, and well tolerated. Phase I-III trials have demonstrated an appropriate dosing range leading to effective analgesia, with minimal adverse effects. The analgesia provided by this system was found to be superior to that of analgesia placebo and equivalent to that of an intravenous morphine PCA. CONCLUSIONS: Data from clinical trials indicated that IONSYS is successful in controlling acute postoperative pain that circumvents the limitations of intravenous patient-controlled analgesia. The use of this system may serve as an alternative modality for the management of acute pain without increasing such adverse effects as bleeding, intravenous catheter infiltration, or manual pump malfunction.

Teduglutide for the treatment of short bowel syndrome.

OBJECTIVE: To summarize the pharmacology, development, and clinical application of teduglutide (ALX-0600), a glucagon-like peptide-2 (GLP-2) analog for the treatment of short bowel syndrome (SBS). DATA SOURCES: Clinical literature, including both primary sources and review articles, was accessed through a search of the MEDLINE databases (1980-March 2006). Key search terms included teduglutide, ALX-0600, glucagon-like peptide-2, short bowel syndrome, short gut, and intestinal adaptation. Clinical trial and drug data were supplied by the manufacturer, NPS Pharmaceuticals. STUDY SELECTION AND DATA EXTRACTION: Review articles, abstracts, and clinical studies related to GLP-2 and its analog, teduglutide, were analyzed. An evaluation of the research exploring teduglutide for the management of SBS was conducted. Relevant information was then selected. DATA SYNTHESIS: Research has revealed that administration of GLP-2 to patients following major small bowel resection improves intestinal adaptation and nutrient absorption. Teduglutide is an enzyme-resistant GLP-2 analog that shows promise in preventing intestinal injury, restoring mucosal integrity, and enhancing intestinal absorptive function. CONCLUSIONS: Data from ongoing clinical trials indicate that teduglutide may have the ability to enhance intestinal absorptive capacity in patients with SBS. Further studies and the completion of Phase III trials are necessary to determine the appropriate dosage and length of treatment for patients with SBS to gain optimal therapeutic benefit from this drug.

Urticaria associated with parenteral nutrition.

We report a 53-year-old female patient with short bowel syndrome who developed urticaria after administration of cyclic parenteral nutrition (PN). The urticaria occurred 2 hours into the 12-hour nocturnal infusion and resolved completely 1 hour after discontinuation of the PN infusion. The urticaria occurred despite removing lipids from the 3-in-1 PN solution. The urticaria did not occur when the multivitamin preparation was removed from the PN. Upon rechallenge with a PN solution containing a multivitamin, the urticaria reoccurred. Prick skin testing using the multivitamin in increasing aliquots was negative. Serum tryptase and 12-hour urinary histamine level during PN infusion containing the multivitamin was unchanged compared with baseline measurements. The patient had no allergic reaction using a similar dose of an oral multivitamin. This case illustrates that allergic reactions from PN infusion may occur and that the multivitamin preparation can be the cause.

Trastuzumab for the treatment of non-small-cell lung cancer.

OBJECTIVE: To evaluate trastuzumab for the treatment of advanced non-small-cell lung cancer (NSCLC). DATA SOURCES: Clinical literature was accessed through MEDLINE (1966-January 2003), EMBASE (1974-January 2003), International Pharmaceutical Abstracts (1970-January 2003), Proceedings of the American Society of Clinical Oncology (1995-January 2003), and Genentech. Key search terms included trastuzumab, lung cancer, Herceptin, and NSCLC. DATA SYNTHESIS: Research has revealed that NSCLC specimens may express the protein HER-2/neu. The monoclonal antibody against HER-2/neu, trastuzumab, could prove valuable for patients. An evaluation of the studies exploring trastuzumab for management of NSCLC was conducted. Phase II clinical trials reveal variable response rates from no improvement to a partial response rate of 42%. Due to a lack of clinical trials and deficiencies in the literature, the ultimate benefit of this agent remains to be proven. CONCLUSIONS: Clinical data from ongoing trials indicate potential synergy when trastuzumab is added to standard chemotherapy. The ultimate benefit in NSCLC remains to be proven.