A phase I study of afatinib combined with paclitaxel and bevacizumab in patients with advanced solid tumors

Purpose The combination of afatinib, an irreversible ErbB family blocker, with paclitaxel and bevacizumab was assessed in patients with advanced solid tumors.Methods This phase I study used a 3 + 3 design to determine the maximum tolerated dose (MTD) of afatinib combined with paclitaxel and bevacizumab. Safety, pharmacokinetics, and anti-tumor activity were also assessed. The starting dose was oral afatinib 40 mg once daily plus intravenous paclitaxel (fixed dose 80 mg/m2, Days 1, 8, and 15 of a 4-week cycle) and intravenous bevacizumab 5 mg/kg every 2 weeks.Results Twenty-nine patients were enroled. The afatinib dose was de-escalated to 30 mg and then 20 mg after 2/6 and 2/5 evaluable patients developed dose-limiting toxicities at 40 and 30 mg, respectively, when combined with paclitaxel and bevacizumab 5 mg/kg. The bevacizumab dose was subsequently escalated to 10 mg/kg, and MTD was defined as afatinib 20 mg plus paclitaxel 80 mg/m2 and bevacizumab 10 mg/kg. Frequent (any grade) treatment-related adverse events (AEs) included diarrhea (83%), rash/acne (83%), fatigue (79%), mucosal inflammation (59%), and nausea (59%). Based on overall safety, bevacizumab was amended to 7.5 mg/kg for the recommended phase II dose. Pharmacokinetic analyses suggested no relevant drug-drug interactions. Three (10%) confirmed partial responses were observed; 15 (52%) patients had stable disease.Conclusions The recommended phase II dose schedule was afatinib 20 mg/day with paclitaxel 80 mg/m2 (Days 1, 8, and 15 every 4 weeks) and bevacizumab 7.5 mg/kg every 2 weeks. At this dose schedule, AEs were manageable, and anti-tumor activity was observed

Consensus in Bladder Cancer Research Priorities Between Patients and Healthcare Professionals Using a Four-stage Modified Delphi Method

We would like to thank the British Association of Urological Surgeons, British UroOncology Group, Action Bladder Cancer UK and Fight Bladder Cancer for their participation in this work. We also like to thank the Dianne and Graham Roberts Charitable Settlement for their support of the TOUR teamPeer reviewedPostprin

Systemic anticancer therapy for urothelial carcinoma: UK oncologists’ perspective

Urothelial carcinoma (UC) is a common cancer associated with a poor prognosis in patients with advanced disease. Platinum-based chemotherapy has remained the cornerstone of systemic anticancer treatment for many years, and recent developments in the treatment landscape have improved outcomes. In this review, we provide an overview of systemic treatment for UC, including clinical data supporting the current standard of care at each point in the treatment pathway and author interpretations from a UK perspective. Neoadjuvant cisplatin-based chemotherapy is recommended for eligible patients with muscle-invasive bladder cancer and is preferable to adjuvant treatment. For first-line treatment of advanced UC, platinum-eligible patients should receive cisplatin- or carboplatin-based chemotherapy, followed by avelumab maintenance in those without disease progression. Among patients unable to receive platinum-based chemotherapy, immune checkpoint inhibitor (ICI) treatment is an option for those with programmed death ligand 1 (PD-L1)–positive tumours. Second-line or later treatment options depend on prior treatment, and enfortumab vedotin is preferred after prior ICI and chemotherapy, although availability varies between countries. Additional options include rechallenge with platinum-based chemotherapy, an ICI, or non–platinum-based chemotherapy. Areas of uncertainty include the optimal number of first-line chemotherapy cycles for advanced UC and the value of PD-L1 testing for UC

COVID-19 Risk Factors for Cancer Patients: A First Report with Comparator Data from COVID-19 Negative Cancer Patients

none32siSimple SummaryThe COVID-19 pandemic has had a detrimental impact on cancer patients globally. Whilst there are several studies looking at the potential risk factors for COVID-19 disease and related death, most of these include non-cancerous patients as the COVID-19 negative comparator group, meaning it is difficult to draw hard conclusions as to the implications for cancer patients. In our study, we utilized data from over 2000 cancer patients from a large tertiary Cancer Centre in London. In summary, our study found that patients who are male, of Black or Asian ethnicity, or with a hematological malignancy are at an increased risk of COVID-19. The use of cancer patients as the COVID-19 negative comparator group is a major advantage to the study as it means we can better understand the true impact of COVID-19 on cancer patients and identify which factors pose the biggest risk to their likelihood of infection with SARS-CoV2.Very few studies investigating COVID-19 in cancer patients have included cancer patients as controls. We aimed to identify factors associated with the risk of testing positive for SARS CoV2 infection in a cohort of cancer patients. We analyzed data from all cancer patients swabbed for COVID-19 between 1(st) March and 31(st) July 2020 at Guy's Cancer Centre. We conducted logistic regression analyses to identify which factors were associated with a positive COVID-19 test. Results: Of the 2152 patients tested for COVID-19, 190 (9%) tested positive. Male sex, black ethnicity, and hematological cancer type were positively associated with risk of COVID-19 (OR = 1.85, 95%CI:1.37-2.51; OR = 1.93, 95%CI:1.31-2.84; OR = 2.29, 95%CI:1.45-3.62, respectively) as compared to females, white ethnicity, or solid cancer type, respectively. Male, Asian ethnicity, and hematological cancer type were associated with an increased risk of severe COVID-19 (OR = 3.12, 95%CI:1.58-6.14; OR = 2.97, 95%CI:1.00-8.93; OR = 2.43, 95%CI:1.00-5.90, respectively). This study is one of the first to compare the risk of COVID-19 incidence and severity in cancer patients when including cancer patients as controls. Results from this study have echoed those of previous reports, that patients who are male, of black or Asian ethnicity, or with a hematological malignancy are at an increased risk of COVID-19.openRussell, Beth; Moss, Charlotte L; Palmer, Kieran; Sylva, Rushan; D'Souza, Andrea; Wylie, Harriet; Haire, Anna; Cahill, Fidelma; Steel, Renee; Hoyes, Angela; Wilson, Isabelle; Macneil, Alyson; Shifa, Belul; Monroy-Iglesias, Maria J; Papa, Sophie; Irshad, Sheeba; Ross, Paul; Spicer, James; Kordasti, Shahram; Crawley, Danielle; Zaki, Kamarul; Sita-Lumsden, Ailsa; Josephs, Debra; Enting, Deborah; Swampillai, Angela; Sawyer, Elinor; Fields, Paul; Wrench, David; Rigg, Anne; Sullivan, Richard; Van Hemelrijck, Mieke; Dolly, SaoirseRussell, Beth; Moss, Charlotte L; Palmer, Kieran; Sylva, Rushan; D'Souza, Andrea; Wylie, Harriet; Haire, Anna; Cahill, Fidelma; Steel, Renee; Hoyes, Angela; Wilson, Isabelle; Macneil, Alyson; Shifa, Belul; Monroy-Iglesias, Maria J; Papa, Sophie; Irshad, Sheeba; Ross, Paul; Spicer, James; Kordasti, Shahram; Crawley, Danielle; Zaki, Kamarul; Sita-Lumsden, Ailsa; Josephs, Debra; Enting, Deborah; Swampillai, Angela; Sawyer, Elinor; Fields, Paul; Wrench, David; Rigg, Anne; Sullivan, Richard; Van Hemelrijck, Mieke; Dolly, Saoirs