Combination Androgen Receptor Inhibition and Docetaxel in Metastatic Castration-sensitive Prostate Cancer: The Next Step in First-line Treatment?

The addition of docetaxel and abiraterone to androgen deprivation therapy (ADT) heralded a new era in the first-line treatment of metastatic castration-sensitive prostate cancer (mCSPC). Following the success of these combination regimens, 3 new trials presented data on using enzalutamide or apalutamide in men with mCSPC, which showed similar success. These seminal trials collectively established the addition of docetaxel, enzalutamide, apalutamide, or abiraterone to ADT as standards in the upfront treatment of mCSPC. Notably, a subset of patients in these more recent trials were treated with a combination of docetaxel, ADT, and androgen receptor signaling inhibitors or maintenance androgen receptor signaling inhibitors after docetaxel and ADT that provided an initial glimpse into the efficacy of these triplet or maintenance strategies. We discuss the implications of these recent findings and place them in context of the current mCSPC treatment landscape.

A Case of Cobalamin Deficiency and Macrocytic Anemia Secondary to Sunitinib.

Sunitinib is an oral tyrosine kinase inhibitor (TKI) commonly used in the treatment of renal cell carcinoma (RCC). Among a broad range of toxicities, anemia and macrocytosis are common in patients treated with sunitinib. Correlation between sunitinib-associated macrocytosis and cobalamin deficiency has been reported in small case series and retrospective analyses, although others have not found an association. Here, we present a case of transfusion-dependent macrocytic anemia with cobalamin and folate deficiency in a patient with RCC treated with sunitinib.

Developments in the use of tyrosine kinase inhibitors in the treatment of renal cell carcinoma.

INTRODUCTION: Renal cell carcinoma (RCC) is among the most commonly diagnosed solid malignancies, but until recently there were few systemic treatment options for advanced disease. Since 2005, the treatment landscape has been transformed by the development of several novel systemic therapies. In particular, tyrosine kinase inhibitors (TKIs) targeting the vascular endothelial growth factor (VEGF) pathway have been instrumental in improving outcomes in patients with metastatic disease. Areas covered: The armamentarium of TKIs available for the treatment of RCC has expanded in recent years. The most active area of research at this time is the development of treatment regimens combining newer-generation TKIs and immune checkpoint inhibitors. Emerging data point to a role for combination therapy in the frontline management of advanced RCC. Other ongoing areas of research include the use of TKIs in the adjuvant setting and the role of cytoreductive nephrectomy within a changing treatment landscape. Expert opinion: Although TKIs and immune checkpoint inhibitors have incrementally improved outcomes for patients with advanced RCC, long-term survival remains poor. The development of regimens combining these agents represents the next step in the evolution of the field. For the clinician, this will offer exciting possibilities and novel challenges.

Long-term Outcomes With Ifosfamide-based Hypofractionated Preoperative Chemoradiotherapy for Extremity Soft Tissue Sarcomas.

OBJECTIVES: The objective of this study was to analyze outcomes for patients with soft tissue sarcoma of the extremities using neoadjuvant ifosfamide-based chemotherapy and hypofractionated reduced dose radiotherapy, followed by limb-sparing surgery. MATERIALS AND METHODS: An Institutional Review Board (IRB)-approved retrospective review of patients treated at a single institution between 1990 and 2013 was performed. In total, 116 patients were identified who received neoadjuvant ifosfamide-based chemotherapy and 28 Gy in 8 fractions of preoperative radiation (equivalent dose in 2 Gray fractions, 31.5 Gy [α/ß 10] 36.4 Gy [α/ß 3]) followed by limb-sparing surgery. Local recurrence (LR), distant failure (DF), and overall survival (OS) were calculated. Univariate and multivariate analysis for LR, DF, and OS were performed using Cox analysis. Statistical significance was set at a P<0.05. RESULTS: Median follow-up was 5.9 years (range, 0.3 to 24 y). Actuarial LR at 3/6 years was 11%/17%, DF at 3/6 years was 25%/35%, and OS at 3/6 years was 82%/67%. On multivariate analysis, only a positive surgical margin was significantly correlated with worse local control (P=0.005; hazard ratio [HR], 18.33; 95% confidence interval (CI), 2.41-139.34). Age over 60 years (P=0.03; HR, 2.34; 95% CI, 1.10-4.98) and tumor size over 10 cm compared with tumor size ≤5 cm (P=0.03; HR, 3.32; 95% CI, 1.15-9.61) were associated with worse OS. CONCLUSIONS: Soft tissue extremity sarcoma patients treated using reduced dose hypofractionated preoperative radiotherapy in combination with ifosfamide-based chemotherapy shows acceptable local control and warrants further investigation.