0
selected
-
1.
Pegilodecakin as monotherapy or in combination with anti-PD-1 or tyrosine kinase inhibitor in heavily pretreated patients with advanced renal cell carcinoma: Final results of cohorts A, G, H and I of IVY Phase I study.
Tannir, NM, Papadopoulos, KP, Wong, DJ, Aljumaily, R, Hung, A, Afable, M, Kim, JS, Ferry, D, Drakaki, A, Bendell, J, et al
International journal of cancer. 2021;(2):403-408
-
-
Free full text
-
Abstract
Interleukin (IL)-10 has anti-inflammatory and CD8+ T-cell-stimulating properties. Pegilodecakin (pegylated recombinant human IL-10) induces intratumoral antigen-specific CD8 + T-cells and upregulates IFNγ and major histocompatibility complexes (MHC) I and II. Pegilodecakin has single-agent activity with manageable toxicity in advanced renal cell carcinama (aRCC) (data cutoff 24 March 2016). Pegilodecakin with pembrolizumab or nivolumab revealed clinical activity in aRCC (data cutoff 1 July 2018). Here, we report for the first time the results of pegilodecakin+ pazopanib, and final results for monotherapy and long-term follow-up with pegilodecakin + anti-programmed cell death 1 (anti-PD-1) inhibitors (data cutoff 19 February 2019). Phase 1/1b multi-cohort dose escalation IVY study enrolled 353 patients. Sixty-six patients with aRCC were treated with pegilodecakin alone or with pazopanib or anti-PD-1 inhibitor in cohorts A, G, H and I (data cutoff 19 February 2019). Primary endpoints included safety and tolerability. Secondary endpoint was tumor response by immune-related response criteria (irRC). Pegilodecakin plus nivolumab or pembrolizumab yielded median progression-free survival (mPFS) of 13.9 months and 6-month PFS probability of 60%, 76% 1-year overall survival (OS) probability and 61% 2-year OS probability. Pegilodecakin monotherapy produced mPFS of 1.8 months, 6-month PFS probability 25%, 1-year OS 50%, and 2-year OS 17%. Median OS was not reached in both combinations. Objective response rates (ORRs) were 33% with pazopanib and 43% with anti-PD-1. Most common Grade 3/4 treatment-related adverse events included anemia, thrombocytopenia and hypertriglyceridemia. In these heavily pretreated renal cell carcinama cohorts of IVY, pegilodecakin+anti-PD-1 inhibitor showed promising clinical activity. Safety profile of pegilodecakin alone and with anti-PD-1 inhibitors was consistent as previously reported.
-
2.
Upper tract urothelial carcinoma topical issue 2016: treatment of metastatic cancer.
Pham, MN, Apolo, AB, De Santis, M, Galsky, MD, Leibovich, BC, Pisters, LL, Siefker-Radtke, AO, Sonpavde, G, Steinberg, GD, Sternberg, CN, et al
World journal of urology. 2017;(3):367-378
-
-
Free full text
-
Abstract
PURPOSE To review the management of metastatic upper tract urothelial carcinoma (UTUC) including recent advances in targeted and immune therapies as an update to the 2014 joint international consultation on UTUC, co-sponsored by the Société Internationale d'Urologie and International Consultation on Urological Diseases. METHODS A PubMed database search was performed between January 2013 and May 2016 related to the treatment of metastatic UTUC, and 54 studies were selected for inclusion. RESULTS The management of patients with metastatic UTUC is primarily an extrapolation from evidence guiding the management of metastatic urothelial carcinoma of the bladder. The first-line therapy for metastatic UTUC is platinum-based combination chemotherapy. Standard second-line therapies are limited and ineffective. Patients with UTUC who progress following platinum-based chemotherapy are encouraged to participate in clinical trials. Recent advances in genomic profiling present exciting opportunities to guide the use of targeted therapy. Immunotherapy with checkpoint inhibitors has demonstrated extremely promising results. Retrospective studies provide support for post-chemotherapy surgery in appropriately selected patients. CONCLUSIONS The management of metastatic UTUC requires a multi-disciplinary approach. New insights from genomic profiling using targeted therapies, novel immunotherapies, and surgery represent promising avenues for further therapeutic exploration.
-
3.
Primary hypothyroidism and isolated ACTH deficiency induced by nivolumab therapy: Case report and review.
Zeng, MF, Chen, LL, Ye, HY, Gong, W, Zhou, LN, Li, YM, Zhao, XL
Medicine. 2017;(44):e8426
-
-
Free full text
-
Abstract
RATIONALE Nivolumab is a monoclonal IgG antibody blocking programmed death receptor-1 (PD1), leading to restoration of the natural T-cell-mediated immune response against the cancer cells. However, it also causes plenty of autoimmune-related adverse events, which often involves endocrine system. PATIENT CONCERNS A 54-year-old male with renal clear cell carcinoma was treated with nivolumab intravenously. Routine monitoring showed elevated thyroid-stimulating hormone and low free thyroxine after the 6th administration of nivolumab. After the 12th administration, he developed general fatigue, recurrent hypoglycemia, and relative hypotension. Laboratory tests showed low sodium, low morning cortisol without correspondence increase of corticotrophin (ACTH). Other pituitary hormones were normal. MRI showed no space-occupying lesions, but heterogeneous enhancement of the pituitary gland. DIAGNOSES Primary hypothyroidism and isolated ACTH deficiency. The etiologies were assumed to be nivolumab induced autoimmune lymphocytic thyroiditis and hypophysitis, respectively. INTERVENTIONS Hormone replacements with levothyroxine and acetate cortisone were given orally. Nivolumab was adjusted to lower dose and longer interval. OUTCOMES The patient felt good after adequate replacement. Nivolumab was returned to routine dose and interval six months later. And the metastasis was not obviously progressed during this time. LESSONS The present report provides the first detailed presentation of combined hypothyroidism and isolated ACTH deficiency induced by nivolumab. Adrenal deficiency often develops insidiously. We suggest routine monitoring of fasting blood-glucose, blood pressure and serum sodium as well as thyroid function during nivolumab and other cancer immunotherapies. When unexpected fatigue, hypoglycemia, hypotension or hyponatremia appeared, adrenal deficiency should be taken into consideration.
-
4.
The Therapeutic Aspects of the Endocannabinoid System (ECS) for Cancer and their Development: From Nature to Laboratory.
Khan, MI, Sobocińska, AA, Czarnecka, AM, Król, M, Botta, B, Szczylik, C
Current pharmaceutical design. 2016;(12):1756-66
-
-
Free full text
-
Abstract
The endocannabinoid system (ECS) is a group of neuromodulatory lipids and their receptors, which are widely distributed in mammalian tissues. ECS regulates various cardiovascular, nervous, and immune system functions inside cells. In recent years, there has been a growing body of evidence for the use of synthetic and natural cannabinoids as potential anticancer agents. For instance, the CB1 and CB2 receptors are assumed to play an important role inside the endocannabinoid system. These receptors are abundantly expressed in the brain and fatty tissue of the human body. Despite recent developments in molecular biology, there is still a lack of knowledge about the distribution of CB1 and CB2 receptors in the human kidney and their role in kidney cancer. To address this gap, we explore and demonstrate the role of the endocannabinoid system in renal cell carcinoma (RCC). In this brief overview, we elucidate the therapeutic aspects of the endocannabinoid system for various cancers and explain how this system can be used for treating kidney cancer. Overall, this review provides new insights into cannabinoids' mechanisms of action in both in vivo and in vitro models, and focuses on recent discoveries in the field.