Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Metastatic or locally advanced squamous cell carcinoma of the penis (SCCP) is generally incurable, but it can be palliated with systemic chemotherapy. Two retrospective studies, involving <10 patients each, showed that cisplatin plus continuous infusion of 5‐fluorouracil (5‐FU) may be effective and well tolerated. Cisplatin, methotrexate and bleomycin, cisplatin and irinotecan and taxanes can also play an important role for patients with locally advanced/metastatic SCCP. Finally, anti‐EGFR therapy may also be effective in advanced SCCP. Although cisplatin plus continuous infusion of 5‐FU is widely used in clinical practice for palliation of SCCP, toxicity and efficacy data regarding this schedule include a total of 14 patients with SCCP, treated more than two decades ago. In our retrospective study, cisplatin plus continuous infusion of 5‐FU was used for palliative purposes in a homogenous sample of 25 patients with SCCP. Partial responses and stable disease were observed in 8 (32%) and 10 (40%) patients, respectively, with a median progression‐free survival of 20 weeks. Neutropenia was the most important grade 3–4 side effect observed, occurring in 20% of patients. These data provide confirmation that such a combination regimen is moderately effective and well tolerated in patients with SCCP. OBJECTIVE: To investigate the activity and toxicity of 5‐fluorouracil (5‐FU) as a first‐line treatment in metastatic squamous cell carcinoma of the penis (SCCP). METHODS: The medical records of 78 patients with SCCP treated between January 2000 and June 2011 at the four participating centres were reviewed. Data regarding patients treated with first‐line 5‐FU were extracted. Patients were included in the study if radiological reports were available for determination of response and progression‐free survival (PFS) according to response evaluation criteria in solid tumours (RECIST) 1.1. RESULTS: Between January 2000 and June 2011, 25 patients were treated with i.v. cisplatin on day 1 followed by 5‐FU as a continuous 24‐h infusion for 4 days every 3 weeks until disease progression or unacceptable toxicity. Partial responses and stable disease were observed in eight (32%) and 10 (40%) patients, respectively, with a disease control rate of 72%. Severe neutropenia was the most important grade 3–4 side effect observed, occurring in 20% of patients. The median (interquartile range [IQR]) PFS was 20 (11–20) weeks and the median (IQR) overall survival (OS) was 8 (7–12) months. CONCLUSION: 5‐FU is associated with a moderate response rate and is well tolerated in patients with metastatic SCCP.

Immune checkpoint inhibitors (ICIs) represent a promising treatment for many kinds of cancers, including hepatocellular carcinoma (HCC). The rationale for using ICIs in HCC is based on the immunogenic background of hepatitis and cirrhosis and on the observation of high programmed death-ligand 1 (PD-L1) expression and tumor-infiltrating lymphocytes in this cancer. Promising data from phase I/II studies in advanced HCC, showing durable objective response rates (~20% in first- and second-line settings) and good safety profile, have led to phase III studies with ICIs as single agents or in combination therapy, both in first and second line setting. While the activity of immunotherapy agents as single agents seems to be limited to an “ill-defined” small subset of patients, the combination of the anti PD-L1 atezolizumab and anti-vascular endothelial growth factor bevacizumab revealed a benefit in the outcomes when compared to sorafenib in the first line. In addition, the activity and efficacy of the combinations between anti-PD-1/anti-PD-L1 antibody and other ICIs, tyrosine kinase inhibitors, or surgical and locoregional therapies, has also been investigated in clinical trials. In this review, we provide an overview of the role of ICIs in the management of HCC with a critical evaluation of the current status and future directions.

A multi-institutional Phase II trial was initiated in 2005 to test the combination gemcitabine and capecitabine in patients with thymic epithelial malignancies (TETs). Patients with histologic confirmation of TET diagnosis by central review who had received >1 systemic chemotherapy treatment were included. Patients received oral capecitabine (650 mg/mq twice daily on days 1-14) and intravenous gemcitabine (1000 mg/mq on days 1 and 8 every 3 weeks). Of the 30 patients included (18 men, 12 women; median age: 57 years, range: 48-61 years), the majority (73%) had thymoma, and the remaining thymic carcinoma. Eight patients developed grade 3-4 neutropenia. A total of 12 patients had a response. Median progression-free survival was 11 months (range: 6.5-16.5). Capecitabine and gemcitabine is highly active in TETs.