No abstract

Checkpoint inhibitors are monoclonal antibodies attach to several different receptors on T-cells or tumour cells expressing receptors for cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed death-1 (PD-1) and their ligand (PD-L1). Since 2010, numerous trials on different tumour types have been conducted, which was resulted in these drugs being approved for the treatment of melanoma, lung cancer, Hodgkin's lymphoma and head and neck cancers. Urological cancers, especially urothelial and renal-cell carcinomas, are immunogenic tumours. Since the late 70s, the bacillus Calmette-Gurin (BCG) vaccine has been used for intravesical instillation in non-muscle invasive bladder cancer from the mid-90s up until the discovery of tyrosine kinase inhibitors (TKIs) in 2007, interleukin-2 (IL-2) and interferon alpha (IFNα), which were the standard of care for metastatic renal-cell cancer. Two checkpoint inhibitors are already approved by the Food and Drug Administration: atezolizumab for metastatic urothelial cancer and nivolumab for metastatic renal-cell carcinoma. There are many drugs are in different phases of clinical development. Here we review the current status of checkpoint inhibitors in the treatment of urological tumours.

Renal cell cancer (RCC) represents 2%-3% of all adulthood cancers and is the most common malignant neoplasm of the kidney (90%). In the mid-nineties of the last century, the standard of treatment for patients with metastatic RCC was cytokines. Sunititib and pazopanib were registered in 2007 and 2009, respectively, and have since been the standard first-line treatment for metastatic clear cell RCC (mccRCC). Renal cell cancer is a highly immunogenic tumor with tumor infiltrating cells, including CD8+ T lymphocytes, dendritic cells, natural killer cells (NK) and macrophages. This observation led to the design of new clinical trials in which patients were treated with immunotherapy. With the growing evidence that proangiogenic factors can have immunomodulatory effects on the host’s immune system, the idea of combining angiogenic drugs with immunotherapy has emerged, and new clinical trials have been designed. In the last few years, several therapeutic options have been approved [immunotherapy and immunotherapy/tyrosine kinase inhibitors (TKI)] for the first-line treatment of mccRCC. Nivolumab/ipilimumab is approved for the treatment of patients with intermediate and poor prognoses. Several checkpoint inhibitors (pembrolizumab, nivolumab, avelumab) in combination with TKI (axitinib, lenvatinib, cabozantinib) are approved for the treatment of patients regardless of their International mRCC Database Consortium prognostic group and PD-L1 expression. There is no specific and ideal biomarker that could help in selecting the ideal patient for the appropriate first-line treatment.

Primary breast lymphoma is rare location of this disease. Diffuse large B-cell lymphoma is the most common histological subtype. We presented two cases of primary diffuse large B-cell lymphoma of the breast and reviewed a literature about this topic

Oncologists worldwide are often dealing with hepatitis C virus positive breast cancer patients, questioning adequate chemotherapy protocol, reduction of doses, delays, or even interruptions of treatment. We present a case of a woman in stage IIIB breast cancer, who after the completion of neoadjuvant treatment developed significant increase in liver enzymes and was diagnosed positive for HCV. She was treated with interferon and after the resolving of acute liver disease continued concomitant treatment with interferon, ribavirin, docetaxel, and trastuzumab. Grade 4 neutropenia and grade 3 hepatotoxicity occurred after the third cycle of chemo and 5 months of antiviral therapy. Interferon and chemotherapy were postponed for 1 week. There are no sufficient data in order to recommend the concomitant antiviral and antineoplastic therapy. Hepatitis C virus and antiviral therapy may increase the toxicities of antineoplastic treatment. However, when lifesaving oncologic treatment is necessary, concomitant antiviral therapy can be administered with more intensive follow up.