Feasibility of cabazitaxel in octogenarian prostate cancer patients.

Background: To evaluate the effectiveness and safety of cabazitaxel in castration-resistant prostate cancer patients aged ≥80 years, we performed a retrospective study on a sample of patients from 11 Italian cancer centers. Materials and methods: Fifty-seven patients aged ≥80 years were treated with cabazitaxel after previous failure with docetaxel; 39 completed a comprehensive geriatric assessment questionnaire (34 fit and 5 vulnerable) and 8 patients (14%) had an Eastern Cooperative Oncology Group performance status (PS) ≥2, while most had a PS of 0-1 (86%). Cabazitaxel was administered at a dose of 25 mg/m2 in 30 (52%) patients and 20 mg/m2 or adapted schedules in 27 (48%) patients. These schedules were adopted mainly in patients ≥85 years (75%), with a PS ≥2 (87.5%), and those classified as vulnerable (100%). Results: The duration of treatment was 4.8 months and was comparable in all subgroups; disease control rate was reported in 36 patients (63%); prostate-specific antigen response was recorded in 18 patients (31.5%). Median overall survival was 13.1 months regardless of age (<85/≥85 years), but overall survival was reduced in vulnerable (7.2 months) and PS ≥ 2 patients (6.8 months). The most frequently documented grade 3-4 toxicities were neutropenia (14%) and diarrhea (10.5%). Six patients (10.5%) dropped out due to severe toxicity. Conclusions: Octogenarian patients can be treated with cabazitaxel with reduced doses or alternative schedules that are associated with less toxicity and fewer treatment interruptions. Comprehensive geriatric assessment could facilitate more appropriate patient selection.

The association of cemiplimab plus sonidegib for synchronous cutaneous squamous cell carcinoma and basal cell carcinoma of the head and neck: Two case reports.

Basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC) are the most frequent cancers in humans, with cumulative ultraviolet radiation exposure, aging, and immunodepression as the main risk factors. In most cases, these malignancies arise in the head and neck area, and they can be treated with locoregional therapies. A minority of cases require systemic therapy. Currently, Sonic Hedgehog inhibitors (i.e., vismodegib and sonidegib) have been approved for advanced BCC, while the PD-1 checkpoint inhibitor cemiplimab has been approved as a first-line treatment for cSCC and as a second-line treatment for BCC. Nevertheless, there is a clinical need for an effective and safe systemic therapies for advanced synchronous (syn) BCC/cSCC not amenable to local treatments. International guidelines do not provide specific recommendations for patients affected by this condition, and no case reports on the full-dose association of these medications have been previously reported. Here, we present the cases of two elderly patients affected by synBCC/cSCC of the head and neck, who received combined therapy with cemiplimab and sonidegib at full dose and standard schedule, achieving remarkable clinical benefit and long-term responses, without major adverse events. The instance of a feasible treatment for patients with advanced synBCC/cSCC will become increasingly frequent with the advancement of life expectancy in the global population, and the synergistic activity of targeted therapies and immunotherapy-administered either in association or sequentially-deserves to be further explored.

Body mass index (BMI) influence on Cetuximab-induced antibody-dependent cellular cytotoxicity in advanced colon cancer.

To date, we do not know if the excess of the body mass index (BMI) improves or worsens the outcomes in colorectal cancer treatment, and the correlation between BMI and prognosis remains unclear. A recent study in vitro showed a significant negative correlation between BMI and Cetuximab-induced antibody-dependent cellular cytotoxicity. On these bases, we tried to analyze the potential correlation between BMI and survival in patients affected by metastatic colorectal cancer (mCRC) and treated with Cetuximab. Retrospective data were collected from 132 patients affected by mCRC treated with Cetuximab in monotherapy or association with chemotherapy between January 2007 and October 2019. The cohort of patients was divided into different groups according to the World Health Organization (WHO) BMI classification: underweight (BMI < 18.59), normal weight (BMI 18.5-24.9,) overweight (BMI 25-29.9), and obese (BMI > 30), and we observed the influence of BMI on survival and treatment response. Patients with BMI ≥ 25 had statistically significantly better survival than patients BMI < 25 (19 vs 10 months, p = 0.025). Dividing the sample into the four WHO BMI categories, the best survival rates were seen in the overweight and obese subgroups (18 and 26 months respectively, p < 0.01). The multivariate analysis confirmed BMI as the only parameter able to influence survival. No correlation between BMI and treatment response was seen between BMI ≥ 25 and BMI ≤ 24 groups (p = 0.14). Our experience suggests that mild obese and overweight patients treated with Cetuximab could experience a better survival. We also observed that among normal weight, overweight, and mild obese patients, there is a better response to immunochemotherapy in comparison with underweight patients, but this difference does not reach a significative statistical value.

Complete testicular remission after chemotherapy in a patient with advanced seminoma: is the testicle a real 'sanctuary'? A case report and review of the literature.

Testicular cancer is relatively uncommon, but at the same time, it is the most common solid tumor in men between the ages of 20 and 34 years. Seminoma represents the most frequently encountered germ cell tumors. Because orchiectomy is usually performed before chemotherapy, little is known about the effect of systemic chemotherapy on primary testicular tumors. Furthermore, the testis has always been considered a sanctuary site, an immune-privileged site in which inadequate exposure of the tumor to chemotherapy may occur. We report the case of a young patient with advanced seminoma with a complete testicular response after four cycles of cisplatin-based chemotherapy. Then, we performed a systematic review of the literature reporting the studies published to date on the topic.

Immunotherapy in Nonendemic Nasopharyngeal Carcinoma: Real-World Data from Two Nonendemic Regions.

BACKGROUND: nasopharyngeal carcinoma (NPC) is a complex disease entity that mainly predominates in endemic regions. Real-world data with immunotherapy from nonendemic regions are limited. METHODS: we collected data from patients with recurrent/metastatic (R/M) NPC treated at a center in Greece and 8 centers in Italy. Between 2016 and 2021, 46 patients who were treated with at least one cycle of immune checkpoint inhibitors (ICI) were identified. Herein, we present our results and a review of the literature. RESULTS: assessment of response was available in 42 patients. Overall, 11 patients responded to immunotherapy (Overall Response Rate-ORR 26.2%). Three patients had complete response (CR), and 8 patients had partial response (PR). Disease control rate (DCR) was 61.9%. Median Progression Free Survival (PFS) was 5.6 months and median Overall Survival (OS) was 19.1 months. Responders to ICI improved PFS and OS as compared to that of nonresponders. A lower probability of responding to ICI was shown in patients with more than three metastatic sites (p = 0.073), metastatic disease at initial diagnosis, (p = 0.039) or EBV DNA positive before ICI initiation, (p = 0.074). Decline in EBV DNA levels was found to be statistically significant associated with best response to ICI (p = 0.049). Safety was manageable. CONCLUSIONS: among 46 patients with R/M NPC treated with immunotherapy in two nonendemic regions, ORR was 26.2% and durable responses were observed. Low disease burden could serve as a biomarker for response to ICI.

Prevention of anthracycline-induced cardiotoxicity: a systematic review and meta-analysis.

Anthracyclines are extensively used in oncologic patients, in particular for breast cancer and hematological malignancies. Cardiac injury is a potentially dangerous side effect of these drugs. In this systematic review, we analyzed published randomized controlled trials (RCTs) to assess if potential cardioprotective drugs (i.e., renin-angiotensin-aldosterone system [RAAS] blockers and ß-blockers) may prevent heart damage by anthracyclines. Studies were identified by electronic search of MEDLINE and EMBASE database until August 2020. The impact of cardioprotective drugs to prevent anthracyclines-induced cardiac injury was expressed as mean difference (MD) or odds ratio (OR) and 95% confidence intervals (95% CI). Statistical heterogeneity was assessed with the I2 statistic. Twelve RCTs for a total of 1.035 cancer patients treated with anthracyclines were included. RAAS blockers, ß-blockers, and aldosterone antagonists showed a statistically significant benefit in preventing left ventricular ejection fraction (LVEF) reduction (MD 3.57, 95% CI 1.04, 6.09) in 11 studies. A non-statistically significant difference was observed in preventing E/A velocity decrease (MD 0.09, 95% CI 0.00, 0.17; 9 studies), left ventricular end-systolic diameter (LVESD) increase (MD - 0.88, 95% CI, - 2.75,0.99; 6 studies), left ventricular end-diastolic diameter (LVEDD) increase (MD -0.95, 95% CI - 2.67,0.76; 6 studies), and mitral A velocity decrease (MD - 1.42, 95% CI - 3.01,0.17; 4 studies). Heart failure was non-significantly reduced in the cardioprotective arm (OR 0.31, 95% CI 0.06, 1.59; 5 studies). Hypotension was non-significantly increased in the cardioprotective arm (OR 3.91, 95% CI 0.42, 36.46, 3 studies). Cardioprotective drugs reduce anthracycline-induced cardiac damage as assessed by echocardiographic parameters. The clinical relevance of this positive effect is still to be defined.