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Fluorine-18-fluorodeoxyglucose-positron emission tomography ((18)F-FDG-PET)-guided focal dose escalation in oropharyngeal cancer may potentially improve local control. We evaluated the feasibility of this approach using volumetric-modulated arc therapy (RapidArc) and compared these plans with fixed-field intensity-modulated radiotherapy (IMRT) focal dose escalation plans. Materials and methods: An initial study of 20 patients compared RapidArc with fixed-field IMRT using standard dose prescriptions. From this cohort, 10 were included in a dose escalation planning study. Dose escalation was applied to (18)F-FDG-PET-positive regions in the primary tumor at dose levels of 5% (DL1), 10% (DL2), and 15% (DL3) above standard radical dose (65 Gy in 30 fractions). Fixed-field IMRT and double-arc RapidArc plans were generated for each dataset. Dose-volume histograms were used for plan evaluation and comparison. The Paddick conformity index (CI(Paddick)) and monitor units (MU) for each plan were recorded and compared. Both IMRT and RapidArc produced clinically acceptable plans and achieved planning objectives for target volumes. Dose conformity was significantly better in the RapidArc plans, with lower CI(Paddick) scores in both primary (PTV1) and elective (PTV2) planning target volumes (largest difference in PTV1 at DL3; 0.81 ± 0.03 [RapidArc] vs. 0.77 ± 0.07 [IMRT], p = 0.04). Maximum dose constraints for spinal cord and brainstem were not exceeded in both RapidArc and IMRT plans, but mean doses were higher with RapidArc (by 2.7 ± 1 Gy for spinal cord and 1.9 ± 1 Gy for brainstem). Contralateral parotid mean dose was lower with RapidArc, which was statistically significant at DL1 (29.0 vs. 29.9 Gy, p = 0.01) and DL2 (29.3 vs. 30.3 Gy, p = 0.03). MU were reduced by 39.8-49.2% with RapidArc (largest difference at DL3, 641 ± 94 vs. 1261 ± 118, p < 0.01). (18)F-FDG-PET-guided focal dose escalation in oropharyngeal cancer is feasible with RapidArc. Compared with conventional fixed-field IMRT, RapidArc can achieve better dose conformity, improve contralateral parotid sparing, and uses fewer MU.

It was a little over a year ago that I first wrote about my quest for employment as a D Grade Staff Nurse; and it was three months later when I wrote of my success in obtaining a post on an infectious diseases unit.

Application of distinct positron emission tomography (PET) scan reconstruction algorithms can lead to statistically significant differences in measuring lesion functional properties. We looked at the influence of two-dimensional filtered back projection (2D FBP), two-dimensional ordered subset expectation maximization (2D OSEM), three-dimensional ordered subset expectation maximization (3D OSEM) without 3D maximum a posteriori and with (3D OSEM MAP) on lesion hypoxia tracer uptake using a pre-clinical PET scanner.Reconstructed images of a rodent tumor model bearing P22 carcinosarcoma injected with hypoxia tracer Copper-64-Diacetyl-bis (N4-methylthiosemicarbazone) (i.e. Cu-64 ATSM) were analyzed at 10 minute intervals till 60 minute post injection. Lesion maximum standardized uptake values (SUVmax) and SUVmax/background SUVmean (T/B) were recorded and investigated after application of multiple algorithm and reconstruction parameters to assess their influence on Cu-64 ATSM measurements and associated trends over time.SUVmax exhibited convergence for OSEM reconstructions while ANOVA results showed a significant difference in SUVmax or T/B between 2D FBP, 2D OSEM, 3D OSEM and 3D OSEM MAP reconstructions across all time frames. SUVmax and T/B were greatest in magnitude for 2D OSEM followed by 3D OSEM MAP, 3D OSEM and then 2D FBP at all time frames respectively. Similarly SUVmax and T/B standard deviations (SD) were lowest for 2D OSEM in comparison with other algorithms.Significantly higher magnitude lesion SUVmax and T/B combined with lower SD were observed using 2D OSEM reconstruction in comparison with 2D FBP, 3D OSEM and 3D OSEM MAP algorithms at all time frames. Results are consistent with other published studies however more specimens are required for full validation.Amaç: Farklı pozitron emisyon tomografisi (PET) rekonstrüksiyon algoritmalarının uygulanması lezyonun fonksiyonel özelliklerinde istatistiksel olarak anlamlı farklılıklara neden olabilir. Bu çalışmada iki-boyutlu filtreli geri projeksiyon (2D FBP), iki-boyutlu düzenli subset expectation maksimizasyonu (2D OSEM), 3D maksimum a posteriori olmaksızın (3D OSEM) ve 3D maksimum a posteriori ile (3D OSEM MAP) üç-boyutlu düzenli subset expectation maksimizasyonu kullanımının pre-klinik bir PET tarayıcısı ile lezyon hipoksisini izleyen maddenin (tracer) tutulumu üzerine etkisi incelenmiştir. Yöntem: P22 karsinosarkomlu bir kemirgen tümör modelinde hipoksi izleyen maddenin Copper-64-Diacetyl-bis (N4- methylthiosemicarbazone) (Cu-64 ATSM) enjeksiyonu ile 60. dakikaya kadar her 10 dakikada bir elde edilen rekonstrükte görüntüler incelendi. Lezyonun maksimum standardize tutulum değeri (SUV max ) ve SUV max /taban SUV ortalama (T/B) değerleri kaydedildi, ve multipl algoritma ve rekonstrüksiyon parametresi uygulanmasından sonra bunların Cu-64 ATSM ölçümleri üzerindeki etkisi ve farklı zaman dilimlerindeki seyri araştırıldı. Bulgular: SUV max OSEM rekonstrüksiyonları için konverjans gösterirken ANOVA sonuçları tüm zaman dilimlerinde 2D FBP, 2D OSEM, 3D OSEM ve 3D OSEM MAP rekonstrüksiyonları arasında SUV max veya T/B de anlamlı farklılık tespit etti. En yüksek SUV max ve T/B değerleri tüm zaman dilimlerinde 2D OSEM’de saptandı, bunu sırasıyla 3D OSEM MAP, 3D OSEM ve 2D FBP takip etti. Benzer şekilde SUV max ve T/B standart deviasyonları (SD) diğer algoritmalara kıyasla 2D OSEM’de en düşüktü. Sonuç: 2D OSEM rekonstrüksiyonu ile 2D FBP, 3D OSEM ve 3D OSEM MAP algoritmalarına kıyasla tüm zaman dilimlerinde anlamlı olarak daha yüksek lezyon SUV max ve T/B ile birlikte daha düşük SD gözlemlendi. Sonuçlar daha önce yayınlanmış çalışmalarla uyumlu olmakla birlikte tam onaylama için daha fazla veri gerekmektedir.

The purpose of this paper is to explore key concepts and ideas surrounding the security challenges of cloud computing, with particular reference to configuration having considerable impact on securing cloud services. It is critical that the concepts of exploitation and vulnerability, which evidence shows exist in Cloud use, are discussed and understood in order to enhance security protection and user awareness. There are considerable benefits of cloud computing systems, however this paper will primarily focus on the limitations that have emerged through inaccurate configuration setups of both the platforms and applications, and how these might be addressed. It also will highlight some research work in the area that offers possible solutions to the identified issues in Cloud security.

Background: Olfactory Neuroblastoma is a rare, locally aggressive malignant neoplasm arising from the olfactory epithelium, which causes metastasis by lymphatic and haematogenous routes, with most common site being the cervical lymph nodes. Materials and Methods: Clinical history was retrieved from discussion in the Head and Neck multidisciplinary team meeting and medical records. Routine macroscopic and microscopic histological examination along with appropriate immunohistochemistry was performed. In addition, we include the review of literature of olfactory neuroblastoma metastatic to different sites. Results: A 75 year old female presented with a left submandibular mass which on biopsy was diagnosed as high grade neuroendocrine carcinoma requiring further investigation for characterising it as primary or metastatic. The histological diagnosis proved difficult and doubtful, till after five months when on follow up investigation a skull base lesion was identified, this on biopsy was confirmed to be an olfactory neuroblastoma. Conclusion: It is important to think laterally and consider metastatic tumours when evaluating neuroendocrine lesions in the submandibular region as this can be the first manifestation.

Shiga toxin 1 (Stx1) and Stx2 produced byEscherichia coliO157 are known to be cytotoxic to Vero and HeLa cells by inhibiting protein synthesis and by inducing apoptosis. In the present study, we have demonstrated that 10 ng/ml Stx2 induced DNA fragmentation in human brain microvascular endothelial cells (HBMEC), with cleavage activation of caspase-3, -6, -8, and -9. A microarray approach used to search for apoptotic potential signals in response to Stx2 revealed that Stx2 treatment induced a marked upregulation of C/EBP homologous protein (CHOP)/growth arrest and DNA damage-inducible protein 153 (GADD153). Increased CHOP expression was dependent on enzymatically active Stx1. Knockdown of CHOP mRNA reduced the activation of caspase-3 and prevented apoptotic cell death. These results suggest that Stx2-induced apoptosis is mediated by CHOP in HBMEC and involves activation of both the intrinsic and extrinsic pathways of apoptosis.

Synthetic cannabinoid (SC) designer drugs based on indole and indazole scaffolds and featuring l-valinamide or l-tert-leucinamide side chains are encountered with increasing frequency by forensic researchers and law enforcement agencies and are associated with serious adverse health effects. However, many of these novel SCs are unprecedented in the scientific literature at the time of their discovery, and little is known of their pharmacology. Here, we report the synthesis and pharmacological characterization of AB-FUBINACA, ADB-FUBINACA, AB-PINACA, ADB-PINACA, 5F-AB-PINACA, 5F-ADB-PINACA, ADBICA, 5F-ADBICA, and several analogues. All synthesized SCs acted as high potency agonists of CB1 (EC50 = 0.24-21 nM) and CB2 (EC50 = 0.88-15 nM) receptors in a fluorometric assay of membrane potential, with 5F-ADB-PINACA showing the greatest potency at CB1 receptors. The cannabimimetic activities of AB-FUBINACA and AB-PINACA in vivo were evaluated in rats using biotelemetry. AB-FUBINACA and AB-PINACA dose-dependently induced hypothermia and bradycardia at doses of 0.3-3 mg/kg, and hypothermia was reversed by pretreatment with a CB1 (but not CB2) antagonist, indicating that these SCs are cannabimimetic in vivo, consistent with anecdotal reports of psychoactivity in humans.

Nationally, less than 50 percent of children reenroll in the State Children's Health Insurance Program (SCHIP), a program for children from families with incomes too high to qualify for Medicaid, but too low to afford private health insurance. To identify why, we surveyed parents who disenrolled children from a North Carolina program in 2004. Seventy-two percent of the respondents knew that their children were disenrolled and 28 percent did not know. The most common reasons parents reported for not reenrolling their children were that they never received the reenrollment forms, or they submitted their forms late. Most said they would pay out of pocket now to purchase health care services for their children. Most respondents took their children to see a provider while enrolled in SCHIP in the last year, and most were satisfied with the care received. We conclude that the goal of increasing children's reenrollment in public health insurance programs requires an improvement in health insurance information, an increase in trust in our social and health institutions, and a reorganization of the reenrollment process.

INTRODUCTION: Glioblastoma multiforme (GBM) is the most common and lethal brain cancer in adults and accounts for 65% of all primary brain tumours. In our unit we routinely utilise fluorescence image guided resection with prior administration of 5-aminolevulinic acid (5-ALA) to the patient for potentially macroscopically resectable GBMs. In the GBM cells 5-ALA is metabolised to protoporphyrin IX, which emits fluorescence when it is excited with violet light, allowing the visualisation of the cancer cells for maximal resection of the tumour. This project looks at the specificity and toxicity of 5-ALA in vitro when characterising the cancer cells isolated from the invasive margin of the tumour. METHODS: Tumour cells are isolated from both the core and the invasive margin of GBM tumours and compared to established cell lines previously derived from the core and to differentiated neural stem cells from mouse cerebellum that were used as a “normal brain” control. Cells were cultured as monolayers, labelled with 5-ALA and analysed by fluorescence microscopy and flow cytometry to determine 5-ALA specific fluorescence. Presto blue assays were carried out to investigate potential toxicity of 5-ALA in vitro. RESULTS: All GBM cells exhibited 5-ALA specific fluorescence whilst the ratio of median fluorescence intensity observed was around 2-fold for the 5-ALA positively labelled compared to the unlabelled cells (SD: 0.51) and no significant fluorescence for the non-neoplastic brain cells. Interestingly, the GBM cells isolated from a recurrent tumour showed some autofluorescence under the microscope. 5-ALA had no toxic effect on the cells. DISCUSSION: The results gained from the fluorescence microscopy and flow cytometry analysis were extremely encouraging and showed that 5-ALA labelling of a mixed population of cells, such as samples obtained from the invasive margin of the tumour, could be used to identify the GBM cells with several downstream applications including cell separation or co-staining. In addition, the technique was found to be non-toxic, with little effect on cell proliferation.

Children are assuming larger roles in household consumer decisions and have also emerged as independent consumers, thus forming an increasingly powerful market segment. Children can be seen as forming, first, a primary market; second, as influencers on their parents’ decision making; and third, as potential future adult consumers. The second role is the main focus of this paper, centring on supermarket purchases. Using focus groups and in-depth interviews, this study explores the influence of children on supermarket shopping. Participants included parents and children of families in Midlothian, Scotland. The results showed that children have a significant influence on supermarket product purchases. The factors which influence children's product preferences are analysed, and their ability to relay their choices to their parents is considered.

SYNOPSISHope is something which we all need in order to live, and which we all seek as we go about our daily lives—hope for our future as well as to encourage us through the despairs and difficulties we all contend with from time to time. This piece is a meditation on stories and philosophies of hope and awe which have inspired me, and which I believe might be an inspiration for others. We are all seeking that which can sustain us and bring us into the presence of the meaning we need in our lives—we are all listening for our own metaphorical ‘violins in Auschwitz’.

Author Summary Background. Combination blockade of human epidermal growth factor receptor (HER) family signaling may confer enhanced antitumor activity than single-agent blockade. We performed a single-arm study of pertuzumab, a monoclonal antibody that inhibits HER2 dimerization, and erlotinib in relapsed non-small cell lung cancer (NSCLC). Methods. Patients received pertuzumab (840-mg loading dose and 420-mg maintenance intravenously every 3 weeks) and erlotinib (150-mg or 100-mg dose orally, daily). The primary endpoint was response rate (RR) by 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) at day 56 in all patients and those with EGFR wild-type tumors. Results. Of 41 patients, 28 (68.3%) experienced treatment-related grade ≥3 adverse events, including pneumatosis intestinalis (3 patients), resulting in early cessation of enrollment. Tissue samples from 32 patients showed mutated EGFR status in 9 of 41 (22%) and wild-type EGFR in 23 of 41 (56%). The FDG-PET RR for patients with assessments at day 56 was 19.5% in all patients (n = 41) and 8.7% in patients with wild-type EGFR NSCLC (n = 23). Investigator-assessed computed tomography RR at day 56 was 12.2%. Conclusion. FDG-PET suggests that pertuzumab plus erlotinib is an active combination, but combination therapy was poorly tolerated, which limits its clinical applicability. More research is warranted to identify drug combinations that disrupt HER receptor signaling but that exhibit improved tolerability profiles.

2529 Background: MSLN is a tumor antigen over-expressed in PC and OC. The ADC DMOT4039A is a humanized IgG1 anti-MSLN monoclonal antibody and anti-mitotic agent, MMAE, that shows anti-proliferative...

Nine children meeting DSM-III-R criteria for Attention Deficit Hyperactivity Disorder (ADHD) and eighteen normal children participated in this study. A screening assessment revealed significantly m...

Fluorine-18-fluorodeoxyglucose-positron emission tomography (¹⁸F-FDG-PET)-guided focal dose escalation in oropharyngeal cancer may potentially improve local control. We evaluated the feasibility of this approach using volumetric-modulated arc therapy (RapidArc) and compared these plans with fixed-field intensity-modulated radiotherapy (IMRT) focal dose escalation plans.An initial study of 20 patients compared RapidArc with fixed-field IMRT using standard dose prescriptions. From this cohort, 10 were included in a dose escalation planning study. Dose escalation was applied to ¹⁸F-FDG-PET-positive regions in the primary tumor at dose levels of 5% (DL1), 10% (DL2), and 15% (DL3) above standard radical dose (65 Gy in 30 fractions). Fixed-field IMRT and double-arc RapidArc plans were generated for each dataset. Dose-volume histograms were used for plan evaluation and comparison. The Paddick conformity index (CI(Paddick)) and monitor units (MU) for each plan were recorded and compared. Both IMRT and RapidArc produced clinically acceptable plans and achieved planning objectives for target volumes. Dose conformity was significantly better in the RapidArc plans, with lower CI(Paddick) scores in both primary (PTV1) and elective (PTV2) planning target volumes (largest difference in PTV1 at DL3; 0.81 ± 0.03 [RapidArc] vs. 0.77 ± 0.07 [IMRT], p = 0.04). Maximum dose constraints for spinal cord and brainstem were not exceeded in both RapidArc and IMRT plans, but mean doses were higher with RapidArc (by 2.7 ± 1 Gy for spinal cord and 1.9 ± 1 Gy for brainstem). Contralateral parotid mean dose was lower with RapidArc, which was statistically significant at DL1 (29.0 vs. 29.9 Gy, p = 0.01) and DL2 (29.3 vs. 30.3 Gy, p = 0.03). MU were reduced by 39.8-49.2% with RapidArc (largest difference at DL3, 641 ± 94 vs. 1261 ± 118, p0.01). ¹⁸F-FDG-PET-guided focal dose escalation in oropharyngeal cancer is feasible with RapidArc. Compared with conventional fixed-field IMRT, RapidArc can achieve better dose conformity, improve contralateral parotid sparing, and uses fewer MU.

In this study, we postulated the beneficial role of oral alanyl-glutamine, a more stable glutamine derivative to decrease 5-fluorouracil (5-FU)-induced mucositis in mice.We measured different morphologic parameters to assess structural changes over time in the small bowel, including crypt depth, villus height, villus area, mitotic and apoptotic indices at the crypt level using terminal deoxyuridine triphosphate nick end labeling, and hematoxylin-eosin staining of ileal tissue. In addition, we analyzed the effect of different alanyl-glutamine concentrations on animal weight curves after 5-FU treatment.Neither glutamine nor alanyl- glutamine prevented the 5-FU intestinal structural damage or apoptosis in crypt enterocytes at 24 h after 5-FU challenge. However, we found that alanyl-glutamine, but not glutamine, speeds intestinal recovery when compared with 5-FU-treated controls (P0.05), predominantly by enhancing mitotic activity and crypt length.Our findings provide important data to support clinical studies of oral alanyl-glutamine in 5-FU-induced mucositis.

2504 Background: NaPi2b (SLC34A2) is a multi-transmembrane, sodium-dependent phosphate transporter expressed in ~70% non-squamous NSCLC and ~90% OC. DNIB0600A is an ADC consisting of a humanized Ig...

5020 Background: Six-transmembrane epithelial antigen of the prostate-1 (STEAP1) protein is a cell-surface antigen overexpressed in human epithelial prostate cancers. The ADC DSTP3086S contains the humanized IgG1 anti-STEAP1 monoclonal antibody linked to the potent anti-mitotic agent MMAE. Methods: This study evaluated safety, pharmacokinetics, and pharmacodynamic activity of intravenous DSTP3086S (0.3-2.8 mg/kg) given every 3 weeks (q3w) to pts with CRPC. A traditional 3+3 design was used to determine maximum-tolerated dose, followed by cohort expansion at the recommended Phase II dose (RP2D). Clinical activity was evaluated per PCWG criteria. Dose escalation results are presented. Results: Twenty-eight pts were enrolled with a median age of 67 (43-76), all ECOG PS 0-1, and with a median of 7 prior systemic regimens (including a median of 4 hormonal and 3 non-hormonal regimens). Pts received a median of 3 doses (range 1-10) of DSTP3086S. Reversible Grade 3 transaminitis DLTs occurred in one pt each in the 2.25 mg/kg and 2.8 mg/kg cohorts. Serious AEs (SAE) related to study drug (3 total) included one DVT (Grade 3) in the 1.5 mg/kg cohort, as well as one GI hemorrhage (Grade 3) and one sepsis event (Grade 5) in the 2.25 mg/kg cohort. The most common related AEs across all doses were fatigue (36%), nausea (32%), constipation (25%), decreased appetite and diarrhea (each 21%), and musculoskeletal pain and vomiting (each 18%). Exposure for total antibody, free MMAE, and conjugated MMAE was dose proportional. Approximately 60% of the tumor samples assessed showed high STEAP1 expression. CTC reductions were most robust at 2.8 mg/kg; 4/4 patients with unfavorable CTCs at baseline (median of 99, range: 21-205) exhibited CTC conversions from unfavorable to favorable (

2507 Background: NaPi2b (SLC34A2) is a multi-transmembrane, sodium-dependent phosphate transporter expressed in non-squamous NSCLC and non-mucinous OC. DNIB0600A is an ADC consisting of a humanized IgG1 anti-NaPi2b monoclonal antibody and anti-mitotic agent, MMAE, that shows anti-proliferative activity in xenograft models. Methods: This study evaluated safety, pharmacokinetics, and pharmacodynamics of DNIB0600A (0.2-2.8 mg/kg) given every 3 weeks (q3w) to pts with NSCLC or OC. A traditional 3+3 design was used for dose escalation followed by expansion by disease at the recommended Phase 2 dose (RP2D). Tumor NaPi2b expression was evaluated in archival tissue. Anti-tumor activity was evaluated per RECIST 1.1. Results: As of 10 Dec 2012, 30 dose escalation pts have enrolled (16 NSCLC; 14 OC), median age 61 (range 45-78), PS 0-1, median number of prior regimens 5 (1-12), received a median of 3 (1-17) doses of DNIB0600A. No DLTs occurred at the maximum assessed dose of 2.8 mg/kg; enrollment in the expansion cohort at 2.4 mg/kg is ongoing. The most common related AEs regardless of Grade were fatigue (43%), decreased appetite (37%), nausea (30%), constipation, dysgeusia, vomiting, and peripheral neuropathy (each 17%), and diarrhea (13%). One pt at 1.8 mg/kg experienced a DLT (Grade 3 dyspnea), however, no additional DLTs occurred through the maximally administered dose of 2.8 mg/kg. Expansion at 2.4 mg/kg was selected based on totality of safety data. No accumulation of total antibody, free MMAE, or conjugated MMAE was observed. Exposure of each analyte was dose proportional. Approximately 70% of NSCLCs and 85% of OC expressed high levels (IHC 2+/3+) of NaPi2b. Of the 18 pts treated at dose levels 1.8-2.8 mg/kg (10 NSCLC; 8 OC) 3 pts had a confirmed partial response (PR) with response durations of 8.8+ (OC), 4.4+ (NSCLC), and 1.4+ (OC) months, censored at data cutoff, and 1 additional pt had an unconfirmed PR (OC). Dose expansion data will be presented. Conclusions: DNIB0600A administered q3w has an encouraging safety profile and evidence of anti-tumor activity in both NSCLC and OC. Further studies are planned. Clinical trial information: NCT01375842.

Background: MUC16 is a large transmembrane protein overexpressed by the majority of ovarian cancers (OC), compared with normal tissues. The role of MUC16 in the pathogenesis of ovarian cancer is unknown; however, MUC16 may facilitate the binding of ovarian tumor cells to mesothelial cells lining the peritoneal cavity, and may inhibit natural killer cell-mediated anti-tumor cytotoxic responses. Conjugation of a highly potent cytotoxic drug to a MUC16-specific monoclonal antibody represents a novel approach to treatment of MUC16-expressing tumors. DMUC5754A is an ADC containing the humanized IgG1 anti-MUC16 monoclonal antibody linked to the potent anti-mitotic agent MMAE and demonstrates anti-tumor activity in MUC16-expressing tumor xenograft models. Methods: This phase I study evaluated safety, pharmacokinetics (PK), and pharmacodynamic (PD) activity of DMUC5754A (0.3-3.2 mg/kg) given every 3 weeks (q3w) to patients with advanced recurrent platinum-resistant OC. A standard 3+3 design was used to determine the maximum-tolerated dose, followed by cohort expansion. Tumor tissue was assessed for expression of MUC16 and other relevant markers. Clinical activity was evaluated per RECIST. Results: Forty-four patients (22 escalation, 22 expansion at 2.4 mg/kg), median age 62 (44-79), ECOG PS 0-1, received a median of 4 doses (range 1-20) of DMUC5754A. Two DLTs, 1 Grade 4 neutropenia and 1 Grade 4 uric acid increase, occurred at the maximally administered dose of 3.2 mg/kg. Grade ≥ 3 related adverse events (AE) occurring in ≥ 5% of patients included fatigue (4 at 2.4 mg/kg; 9% total) and neutropenia (1 at 3.2 mg/kg, 3 at 2.4 mg/kg; 9% total). The most common related AEs over all dose levels were fatigue (57%), nausea (34%), vomiting (27%), decreased appetite (25%), peripheral neuropathy (25%), and diarrhea (23%). Serious drug-related AEs (SAE) were small intestine obstruction (2 patients), hypocalcemia (1 patient), and neutropenia (1 patient). Total antibody and conjugated MMAE were not impacted by circulating CA125 and displayed dose-dependent PK with clearance decreasing as dose increased. Accumulation of total antibody, conjugated MMAE and free MMAE was not observed due to their short half-lives (≤5 days). Tumor MUC16 expression was evaluable in 42 patients, showing 20% IHC 0, 16% IHC 2+, and 64% IHC 3+. All confirmed responses (1 CR and 4 PRs) occurred in patients treated at 2.4 mg/kg and whose tumors were MUC16 IHC 2+ or 3+. Six additional patients had minor responses (3 at 2.4 mg/kg). Sixteen of the twenty-nine patients at 2.4 mg/kg were on study ≥ 105 days. Human epididymis protein 4 was a potential surrogate marker for serologic response measures in the presence of anti-MUC16/CA125-binding therapy. Conclusions: DMUC5754A at 2.4 mg/kg q3w has an encouraging safety profile and evidence of anti-tumor activity in MUC16-expressing OC. Further studies are planned. Citation Format: Joyce Liu, Kathleen Moore, Michael Birrer, Suzanne Berlin, Ursula Matulonis, Jeffrey Infante, Jian Xi, Robert Kahn, Yulei Wang, Katie Wood, Daniel Coleman, Daniel Maslyar, Eric Humke, Howard Burris. Targeting MUC16 with the antibody-drug conjugate (ADC) DMUC5754A in patients with platinum-resistant ovarian cancer: A phase I study of safety and pharmacokinetics. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-290. doi:10.1158/1538-7445.AM2013-LB-290