Kaur, Judith S.

8041 Background: ABT-510 is a synthetic peptide analog of thrombospondin-1 demonstrating inhibition of VEGF/bFGF mediated human endothelial cell migration, proliferation, tube formation, cornea-neovascularization as well as inhibition of tumor growth in vivo (B16F10 melanoma). Having been found to be safe in phase I testing, ABT-510 has entered phase II trials. Presented are the results of a phase II study using ABT-510 for the treatment of stage IV melanoma. Methods: A two stage phase II clinical trial was conducted to assess the anti-tumor activity, safety profile and pharmacodynamics of ABT510 in patients with stage IV melanoma. Patients self-administered 100mg of ABT-510 subcutaneously twice/day. Therapy was continued in the absence of excessive toxicity or tumor progression. Primary endpoint was 18 week progression free survival rate. Enrolled were patients at least 18 years of age with measurable (RECIST) metastatic melanoma, ECOG performance status of 0–2 and normal pre-registration blood tests. Exclusion criteria included: cancer therapy less than 4 weeks prior to registration; failure to recover from prior therapy; brain metastases; significant recent bleeding; uncontrolled hypertension; and ongoing anti-coagulation. Pregnant or nursing women were not eligible. Results: Twenty-one patients (67% male) were enrolled with a median age of 55 years. Most patients had M1c disease (80%) and 62% had prior chemotherapy for stage IV melanoma. None of the patients were ineligible/canceled participation. After the first stage of the trial was complete, only 3 of the first 20 patients enrolled were progression-free at 18 weeks. Having not met the minimal clinical efficacy requirement (at least 7 of the first 20 patients progression-free at 18 weeks) the trial was closed to further accrual. Correlative laboratory studies suggested decreases in some of the measured parameters of angiogenesis (VEGFC, circulating endothelial cells) with no impact on immune homeostasis. Conclusions: Single agent ABT-510 therapy administered at 100mg twice/day to patients with previously treated metastatic melanoma did not demonstrate significant clinical efficacy. However, changes in measured parameters of angiogenesis suggest possible clinical efficacy with higher dosing or in combination with cytotoxic therapy. [Table: see text]

Objective: This study sought to understand the patients’ perspective of what contributes to an absence of discussions of sexual orientation (SO), gender identity (GI), and sexual health in cancer care. Methods: Patients were recruited from oncology, gynecology, and a gender transition clinic to participate in semistructured interviews, which were analyzed with qualitative methods. Results: A total of 25 patients were interviewed, shedding light on 2 themes. The first was that these conversations are important but infrequent. One patient explained, “…. we know people who have had sex changes…[they] would have appreciated that question.” In response to whether sexual health was ever brought up, one patient responded, “No doctor ever has.” Patients described unaddressed issues: “There have been times, you know, we’ve wondered if it was okay to make love.” The second theme consisted of 4 pragmatic, patient-provided points to facilitate discussions: (1) implementation of a scale of 1 to 10 (with 10 being comfortable) to first gauge patients’ comfort in talking about SO, GI, and sexual health; (2) having the health-care provider explore the topic again over-time; (3) making sure the health-care provider is comfortable, as such comfort appears to enhance the patient’s comfort (“I have a doctor here, a female doctor, who just matter of fact will ask if I get erections and so on because of the medication she’s giving me);” and (4) eliminating euphemisms (one patient stated, “I don’t know what you mean by ‘sexual health’.”). Conclusion: Oncology health-care providers have a unique opportunity and responsibility to address SO, GI, and sexual health.

5028 Background: Edmonston vaccine strains of MV have significant antitumor activity against ovarian cancer xenografts (Peng et al, Cancer Res, 2002). Oncolytic selectivity is due to overexpression of the MV CD46 receptor in ovarian cancer cells. Furthermore, engineering the virus to express the marker peptide CEA (MV-CEA) allows real time monitoring of viral gene expression/propagation in vivo. Methods: We are conducting a Phase I trial of MV-CEA in patients (pts) with recurrent, taxol and platinum refractory, ovarian or primary peritoneal carcinoma. Eligible pts should have protective anti-MV antibody (ab) titers and normal CEA levels. A standard phase I cohorts of three statistical design is employed. MV-CEA is administered IP via a port-a-cath, q 4 wks for up to 6 cycles. Results: To date, 12 pts have received viral doses from 103 to 106 TCID50. No dose-limiting toxicity has been observed. Most common toxicities included grade 1–2 nausea (4 pts); grade 1–2 fatigue (4 pts); grade 1 fever (3 pts); grade 1 abdominal pain (2 pts). One pt had grade 2–3 arthralgias in cycles 4–6. There was no treatment induced immunosuppression as assessed by DTH, CD4, CD8, immunoglobulin and complement levels, no significant increase in the titers of anti-MV abs in serum or ascites in response to treatment, and no development of anti-CEA abs. Viral genomes were detected in the peripheral blood mononuclear cells of 2 asymptomatic pts by QRT-PCR. No CEA elevation in the serum was observed in the dose range tested, and there was no viral shedding in urine or mouth gargle specimens. Testing of pt tumor samples for CD46 by IHC demonstrated overexpression of the target receptor in 7/8 pts. Best objective response was stable disease (2 - 9 mo duration) in 5 pts, while 3 pts had significant decrease in CA125 levels, of 44%, 72%, and 78%, respectively. Conclusions: In this first human application of an engineered oncolytic MV strain, we have observed excellent tolerance after repeat IP administration of the virus. Despite the low doses employed so far, there is early evidence of biologic activity. Dose escalation continues to the target dose of 109 TCID50. No significant financial relationships to disclose.

8530 Background: RAD-001 (Everolimus) is an oral inhibitor of mammalian target of rapamycin (mTOR). Interim analysis results from a phase II study of RAD-001 in patients with metastatic melanoma (MM) were presented at ASCO 2005. This study was re-opened using a higher dose based on an improvement in the 16 week progression free survival (PFS) rate and good tolerability. Methods: A two- stage, phase II multi-institutional trial was conducted in patients with MM to assess that 16 weeks PFS rate was at least 50%. Inclusion criteria: measurable disease, ECOG performance score of 0–2. Exclusion criteria: presence of intracranial metastases, concurrent use of inducers of cytochrome 3A4 and abnormal organ function. The dose of RAD-001 in the second cohort was increased to 10 mg daily (increased from 30 mg weekly) based on evidence of safety of the higher dose. Results: Twenty-nine patients were enrolled; baseline information is available on 27. Median age was 63 yrs; 15 (56%) had >2 sites of metastatic disease. Most (48%) had stage M1c disease. PS was 0, 1 and 2 in 58%, 38% and 4%. All but 4 (15%) had received prior therapy. Grade 3 adverse events included stomatitis and fatigue (2 each), leukopenia, neutropenia, diarrhea, anorexia, dehydration, dyspnea, hyperglycemia, and hypersensitivity (1 each). Planned interim analysis was done after 20 patients were enrolled. 14 (70%) had progressed 16 weeks, failing to meet the decision rule needed (PFS >30%) to restart accrual. The median PFS for all 29 patients was 56 days. The median overall survival (OS) has not been reached. For the entire cohort of 53 pts treated on this study (at both dose levels), the median PFS, median OS were 59 and 286 days respectively. Conclusion: Interim analysis after enrollment of 20 patients at a higher dose of RAD-001 demonstrated significantly more toxicity and no added clinical efficacy. The 16 week PFS rate target was not reached, and accrual was suspended. No significant financial relationships to disclose.

Background: Palliative medicine physicians are challenged by lack of guidance regarding effectiveness and dosing of cannabis products in the setting of their emerging popularity. Objective: The aim of this study was to describe early patterns of tetrahydrocannabinol (THC) and cannabidiol (CBD) use in Florida following passage of the state’s first medical marijuana law. We describe here the perceived benefits, side effects, and beliefs expressed by patients in a single outpatient academic palliative medicine practice. Methods: A cross-sectional survey was performed of a sequential convenience sample of patients who presented to an outpatient academic palliative medicine clinic over a 3-month period. Results: In all, 24% (14/58) of respondents reported THC use, with half using THC on a daily basis. Patients reported improvements in pain, appetite, and nausea. In all, 71% (10/14) began using THC after the diagnosis of their chronic illness, and the most common form of usage was vaping. In all, 24% (14/58) of patients reported CBD use. Patients reported improvements in pain, and the most common form of usage was topical application. None of the patients had used CBD prior to the onset of their chronic illness. In all, 21% (3/14) of THC users and 21% (3/14) of CBD users thought that their substance was helping to cure their illness. Individual reported side effects in both groups were minimal. Conclusions: Approximately a quarter of outpatient palliative care patients use THC or CBD, often on a daily basis. Palliative care providers should be aware of the frequency, diverse usage, and beliefs behind cannabis product use in this patient population.

Background: Although national organizations advocate that health-care providers ask patients about sexual health and sexual and gender minority status—to learn, for example, about side effects of treatment and to understand patients’ social support—these conversations often do not occur. This study explored health-care providers’ reasons for having/not having these conversations. Methods: This single-institution study recruited health-care providers from medical oncology, hematology, radiation oncology, and gynecology. Face-to-face interviews were recorded, transcribed, and analyzed qualitatively. Results: Three main themes emerged: (1) patient-centric reasons for discussing/not discussing sexual health and sexual and gender minority status (“So I think just the holistic viewpoint is important”); (2) health-care provider–centric reasons for discussing/not discussing these issues (“That’s going to take more time to talk about and to deal with…” or “I was raised orthodox, so this is not something we talk about…”; and (3) reasons that appeared to straddle both of the above themes (eg, acknowledgment of the sometimes taboo nature of these topics). Conclusion: Although many health-care providers favor talking with patients with cancer about sexual health and sexual and gender minority status, limited time, personal reluctance, and the taboo nature of these topics appear at times to hamper the initiation of these conversations.

Abstract Background: Cancer incidence rates for American Indian and Alaska Native (AI/AN) populations vary by geographic region in the United States. The purpose of this study is to examine cancer incidence rates and trends in the AI/AN population compared with the non-Hispanic white population in the United States for the years 2010 to 2015. Methods: Cases diagnosed during 2010 to 2015 were identified from population-based cancer registries and linked with the Indian Health Service (IHS) patient registration databases to describe cancer incidence rates in non-Hispanic AI/AN persons compared with non-Hispanic whites (whites) living in IHS purchased/referred care delivery area counties. Age-adjusted rates were calculated for the 15 most common cancer sites, expressed per 100,000 per year. Incidence rates are presented overall as well as by region. Trends were estimated using joinpoint regression analyses. Results: Lung and colorectal cancer incidence rates were nearly 20% to 2.5 times higher in AI/AN males and nearly 20% to nearly 3 times higher in AI/AN females compared with whites in the Northern Plains, Southern Plains, Pacific Coast, and Alaska. Cancers of the liver, kidney, and stomach were significantly higher in the AI/AN compared with the white population in all regions. We observed more significant decreases in cancer incidence rates in the white population compared with the AI/AN population. Conclusions: Findings demonstrate the importance of examining cancer disparities between AI/AN and white populations. Disparities have widened for lung, female breast, and liver cancers. Impact: These findings highlight opportunities for targeted public health interventions to reduce AI/AN cancer incidence.

End of life is difficult for all patients but sexual and gender minorities (SGM) are prone to isolation and loneliness, especially if their SGM status is unknown or unaccepted. In oncology clinics, where goals of care discussions about end of life are integral and frequent, querying patients about their SGM status and sexual health is of particular importance. The American Society of Clinical Oncology recently released a position statement that called for greater focus on SGM populations with the goal of reducing and eventually eliminating disparities in cancer care within this group. An important first step in addressing such disparities is learning how best to train cancer health-care providers to ask patients about their SGM status and about sexual health in general. This article summarizes the mandate for understanding cancer issues in SGM populations and the dearth of cancer-related data within this group. This article also describes an ongoing 3-part study intended to build a mini curriculum with the goal of helping cancer health-care providers to ask patients with cancer about SGM status and to ask all patients with cancer about sexual health issues. The results of this ongoing study could potentially improve end-of-life care for subgroups of patients.

In 2006, the Indian Health Service (IHS) and the National Cancer Institute (NCI) collaborated to develop an interdisciplinary palliative training program for health professionals in the Indian health system. Their goal was to improve clinician knowledge and skills in palliative care, to train future trainers, and to increase access to palliative care for American Indians and Alaska Natives. The combined program of participant self-study utilizing a multimedia CD-ROM and train-the-trainer seminars followed the curriculum entitled Education in Palliative and End-of-Life Care for Oncology (EPEC ™ -O) with American Indian and Alaska Native Cultural Considerations. Three seminars trained 89 interdisciplinary health providers from throughout the Indian health system. Evaluations demonstrated increased clinician self-reported knowledge and confidence to train and high satisfaction with training. Forty-two of 67 participants completed an anonymous post-conference Web questionnaire. Nearly half had con ducted or definitively planned palliative education sessions, and 57 percent started new palliative services at their practice sites.