Parathyroid Hormone-Related Peptide Secretion From a Pancreatic Neuroendocrine Tumor: A Rare Case Report of Severe Hypercalcemia.

Background/Objective: Hypercalcemia is a common occurrence associated with malignancy, due to a number of causes: (1) lytic bone metastases, (2) production of 1,25-dihydroxyvitamin D from lymphoma, and (3) parathyroid hormone-related peptide (PTHrP) secretion usually from solid tumors. Case Report: A 56-year-old woman presented with symptoms of severe hypercalcemia. Investigations determined that this was due to PTHrP secretion from a pancreatic neuroendocrine tumor (pNET), a noted complication in 1.1% of pNET cases. Although unfit for curative therapy, the patient was treated with fluid replacement, bisphosphonates, calcitonin, and denosumab. After treatment, she had recurrent severe symptomatic hypercalcemia on several occasions despite adjunctive therapy with a somatostatin analog. Ultimately, the patient died as a result of refractory hypercalcemia. Discussion: The hypercalcemia that is rarely associated with PTHrP secretion from pNETs is aggressive and often refractory to the usual medical treatment of hypercalcemia of malignancy. Effective treatment requires cytoreduction of the causative tumor. Denosumab, a receptor activator of nuclear factor kappa beta ligand inhibitor, has proven useful in some cases. Conclusion: This challenging case highlighted the rare but potentially fatal association of pNET with hypercalcemia. Hypercalcemia was the main cause of mortality in an otherwise relatively indolent malignancy.

First-in-human phase I/II, open-label study of the anti-OX40 agonist INCAGN01949 in patients with advanced solid tumors.

BACKGROUND: OX40 is a costimulatory receptor upregulated on antigen-activated T cells and constitutively expressed on regulatory T cells (Tregs). INCAGN01949, a fully human immunoglobulin G1κ anti-OX40 agonist monoclonal antibody, was designed to promote tumor-specific immunity by effector T-cell activation and Fcγ receptor-mediated Treg depletion. This first-in-human study was conducted to determine the safety, tolerability, and preliminary efficacy of INCAGN01949. METHODS: Phase I/II, open-label, non-randomized, dose-escalation and dose-expansion study conducted in patients with advanced or metastatic solid tumors. Patients received INCAGN01949 monotherapy (7-1400 mg) in 14-day cycles while deriving benefit. Safety measures, clinical activity, pharmacokinetics, and pharmacodynamic effects were assessed and summarized with descriptive statistics. RESULTS: Eighty-seven patients were enrolled; most common tumor types were colorectal (17.2%), ovarian (8.0%), and non-small cell lung (6.9%) cancers. Patients received a median three (range 1-9) prior therapies, including immunotherapy in 24 patients (27.6%). Maximum tolerated dose was not reached; one patient (1.1%) receiving 350 mg dose reported dose-limiting toxicity of grade 3 colitis. Treatment-related adverse events were reported in 45 patients (51.7%), with fatigue (16 (18.4%)), rash (6 (6.9%)), and diarrhea (6 (6.9%)) being most frequent. One patient (1.1%) with metastatic gallbladder cancer achieved a partial response (duration of 6.3 months), and 23 patients (26.4%) achieved stable disease (lasting >6 months in one patient). OX40 receptor occupancy was maintained over 90% among all patients receiving doses of ≥200 mg, while no treatment-emergent antidrug antibodies were detected across all dose levels. Pharmacodynamic results demonstrated that treatment with INCAGN01949 did not enhance proliferation or activation of T cells in peripheral blood or reduce circulating Tregs, and analyses of tumor biopsies did not demonstrate any consistent increase in effector T-cell infiltration or function, or decrease in infiltrating Tregs. CONCLUSION: No safety concerns were observed with INCAGN01949 monotherapy in patients with metastatic or advanced solid tumors. However, tumor responses and pharmacodynamic effects on T cells in peripheral blood and post-therapy tumor biopsies were limited. Studies evaluating INCAGN01949 in combination with other therapies are needed to further evaluate the potential of OX40 agonism as a therapeutic approach in patients with advanced solid tumors. TRIAL REGISTRATION NUMBER: NCT02923349.

Tumour Lysis Syndrome in Occult Breast Cancer Treated With Letrozole - A Rare Occurrence. A Case Report and Review.

Tumour lysis syndrome (TLS) is a medical emergency occurring when large numbers of cancer cells rapidly undergo cell death. The resultant metabolic abnormalities results in significant morbidity and mortality. Tumour lysis syndrome most commonly occurs in 5% of haematological malignancies and is less commonly described in solid organ cancers. In breast cancer, TLS has been reported to occur both spontaneously and as a result of cancer chemotherapy, targeted therapy, or radiotherapy. However, only 1 TLS case in a breast cancer patient has been reported as a consequence of aromatase inhibitor letrozole. With the increased recent use of CDK4/6 inhibitors, 2 cases of hyperuricaemia in patients with breast cancer treated with palbociclib/letrozole combination treatment have also been reported. We present the second case of letrozole-induced TLS in a 74-year-old woman with occult breast adenocarcinoma. Despite treatment with recombinant urate oxidase and intravenous fluids, the patient deteriorated and was discharged with hospice care. Although rare, this life-threatening condition should be considered in an acutely unwell patient commencing treatment for solid malignant tumours.

Testicular cancer: a 13-year retrospective review of ethnic disparities in the Waikato region, New Zealand.

BACKGROUND: The testicular cancer incidence in New Zealand is rising. We evaluated if testicular cancer outcomes differed by ethnicity in NZ. AIMS: To study if ethnic disparities existed among testicular cancer patients and their outcomes treated at Waikato Regional Cancer Centre. METHODS: Retrospective review of testicular cancer cases in the Medical Oncology database, Waikato Hospital, between 2001 and 2013 inclusive. RESULTS: Three hundred and twenty-five patients were seen, with median follow up of survivors being 101 (range 13-230) months. 95 (29.2%) were Maori, 210 (64.6%) NZ European and 20 (6.1%) of other ethnicity. One hundred and eighty-two patients were diagnosed with seminoma and 143 with non-seminoma. Maori represented 27.5% of seminoma and 31.4% of non-seminoma patients. Median age at diagnosis was 39 years for seminoma and 30 years for non-seminoma; Maori were significantly younger than non- Maori for both seminoma (median age 35 versus 42 years) and non-seminoma (median age 28 vs 34 years, respectively). While stage distribution of seminoma at diagnosis was similar for Maori and non-Maori (chi-squared P = 0.31), significantly more Maori had higher-stage non-seminoma than non-Maori (stage III in 44% and 22%, respectively, chi-squared P = 0.014). Survival for seminoma (logrank P = 0.19) and non-seminoma (logrank P = 0.89) patients did not differ significantly by ethnicity. CONCLUSIONS: Maori patients were younger at diagnosis of testicular cancer and presented with more advanced non-seminoma testicular tumours compared with non-Maori but survival was comparable.