The role of carboplatin in combination with paclitaxel in patients with castration-resistant prostate cancer.

Background: The aim of the present study was to examine the efficacy of carboplatin in combination with paclitaxel in patients with metastatic castration-resistant prostate cancer pretreated with multiple regimens including docetaxel and androgen receptor-targeted agents. Methods: Clinical data from patients treated with carboplatin plus paclitaxel were collected retrospectively from a single institution. Results: 43 patients with metastatic castration-resistant prostate cancer were identified. Median number of cycles was ten (range: 1 to 23), prostate-specific antigen response was observed in 18 (42%) patients, median progression-free survival was 115 days and median overall survival was 8.1 months. Conclusion: Combination chemotherapy using taxane with carboplatin is an effective and well-tolerated therapy in heavily pretreated patients with metastatic castration-resistant prostate cancer.

The prognosis of metastatic castration-resistant prostate cancer (mCRPC) refractory to docetaxel is poor, with only limited guidance on the optimal treatment strategy. We reviewed patients with mCRPC treated with weekly carboplatin/paclitaxel in a single institution, analyzing their prostate-specific antigen (PSA) response, progression-free survival, treatment duration and overall survival (OS). Potential predictive biomarkers and tolerability were evaluated. 43 patients treated between 2012 and 2020 were identified, including 40 refractory to docetaxel. 19 (44%) had received two prior chemotherapy regimens and 38 (88%) were pretreated with androgen receptor-targeted agents; 18 patients (42%) had bone-only disease and 16 (37%) had visceral disease. Median number of cycles was ten (range: 1 to 23), PSA response (>50% decline) was observed in 18 patients (42%), median progression-free survival was 115 days and median OS was 8.36 months. 11 patients (26%) experienced reversible grade 3 or 4 toxicity, two (5%) had febrile neutropenia, and no lethal adverse events were observed. The prognostic role for OS was confirmed for PSA response, higher line of therapy, pretreatment with enzalutamide, longer response to androgen-deprivation therapy and response to docetaxel. In conclusion, combination chemotherapy with carboplatin/paclitaxel is a viable, effective and well-tolerated therapy in heavily pretreated patients with mCRPC, but should be validated in a prospective trial.

The Role of Cytoreductive Nephrectomy in Renal Cell Carcinoma with Sarcomatoid Histology: A Case Series and Review of the Literature.

BACKGROUND: Renal cell carcinoma with sarcomatoid dedifferentiation represents a rare histological entity characterized by aggressive behavior, limited efficacy of tyrosine kinase inhibitors or mTOR inhibitors, and poor outcome. The immune checkpoint inhibitor therapy regimen combining ipilimumab with nivolumab represents a new standard of care for this patient population due to a hitherto unprecedented response rate and overall survival. On the other hand, the role of cytoreductive nephrectomy in metastatic renal cell carcinoma, in particular, with sarcomatoid histology, remains controversial. PATIENT AND METHODS: In the present case series, we report six patients with locally advanced or synchronous metastatic sarcomatoid renal cell carcinoma and intermediate or poor International Metastatic RCC Database Consortium (IMDC) risk score, five of whom were successfully subjected to cytoreductive nephrectomy. RESULTS: All six patients received the combination regimen of ipilimumab with nivolumab. Five of these patients underwent upfront cytoreductive nephrectomy followed by systemic treatment without any significant delay, with a durable treatment outcome. Notably, two patients with poor prognostic features achieved a long-term major partial response to therapy. We also performed a review of the literature on optimal treatment strategies for patients with sarcomatoid renal cell carcinoma. CONCLUSION: Herein, we highlight the feasibility of performing cytoreductive nephrectomy in patients with intermediate/poor prognosis metastatic renal cell carcinoma with sarcomatoid dedifferentiation followed by immunotherapy with ipilimumab and nivolumab. To enhance the chances of immunotherapy success, cytoreductive nephrectomy should also be considered for patients presenting with a disease with adverse prognostic parameters.

From Tumor Immunology to Immunotherapy in Gastric and Esophageal Cancer.

Esophageal and gastric cancers represent tumors with poor prognosis. Unfortunately, radiotherapy, chemotherapy, and targeted therapy have made only limited progress in recent years in improving the generally disappointing outcome. Immunotherapy with checkpoint inhibitors is a novel treatment approach that quickly entered clinical practice in malignant melanoma and renal cell cancer, but the role in esophageal and gastric cancer is still poorly defined. The principal prognostic/predictive biomarkers for immunotherapy efficacy currently considered are PD-L1 expression along with defects in mismatch repair genes resulting in microsatellite instability (MSI-H) phenotype. The new molecular classification of gastric cancer also takes these factors into consideration. Available reports regarding PD-1, PD-L1, PD-L2 expression and MSI status in gastric and esophageal cancer are reviewed to summarize the clinical prognostic and predictive role together with potential clinical implications. The most important recently published clinical trials evaluating checkpoint inhibitor efficacy in these tumors are also summarized.