NET-02: a randomised, non-comparative, phase II trial of nal-IRI/5-FU or docetaxel as second-line therapy in patients with progressive poorly differentiated extra-pulmonary neuroendocrine carcinoma.

Background: The prognosis for patients with poorly-differentiated extra-pulmonary neuroendocrine carcinoma (PD-EP-NEC) is poor. A recognised first-line (1L) treatment for advanced disease is etoposide/platinum-based chemotherapy with no standard second-line (2L) treatment.

Methods: Patients with histologically-confirmed PD-EP-NEC (Ki-67 > 20%; Grade 3) received IV liposomal irinotecan (nal-IRI) (70 mg/m free base)/5-FU (2400 mg/m)/folinic acid, Q14 days (ARM A), or IV docetaxel (75 mg/m), Q21 days (ARM B), as 2L therapy.

COVID-19 and liver cancer: lost patients and larger tumours.

Background: Northern England has been experiencing a persistent rise in the number of primary liver cancers, largely driven by an increasing incidence of hepatocellular carcinoma (HCC) secondary to alcohol-related liver disease and non-alcoholic fatty liver disease. Here we review the effect of the COVID-19 pandemic on primary liver cancer services and patients in our region.

Objective: To assess the impact of the COVID-19 pandemic on patients with newly diagnosed liver cancer in our region.

Neutrophils: driving progression and poor prognosis in hepatocellular carcinoma?

Background: Irrespective of the underlying aetiology, 90% of hepatocellular carcinomas arise and progress on a background of chronic inflammation. We have explored the independent prognostic value of circulating inflammatory cells.

Methods: Peripheral blood count data sets from 583 consecutive patients presenting to a single UK centre (2000-2010) were analysed for associations with tumour stage, liver function, performance status (PST) and survival.

The use of circulating biomarkers in early clinical trials in patients with cancer.

The development of targeted therapies has changed the approach to early oncological clinical trial design. Identification of patient populations most likely to derive benefit and the biologically effective dose are now as important as determination of the maximum tolerated dose. Completion of the 'pharmacological audit trail' highlights drugs most likely to progress through to license, so resources can be allocated appropriately.

Phase I Study of Lapatinib and Pemetrexed in the Second-Line Treatment of Advanced or Metastatic Non-Small-Cell Lung Cancer With Assessment of Circulating Cell Free Thymidylate Synthase RNA as a Potential Biomarker.

Introduction: Lapatinib is a dual tyrosine kinase inhibitor that targets epidermal growth factor receptor and HER2. We report on a dose-escalation study of lapatinib combined with pemetrexed in second-line treatment to evaluate the safety and efficacy in advanced or metastatic non-small-cell lung cancer (NSCLC) and an exploratory study in which circulating cell-free thymidylate synthase ribonucleic acid (cfTSmRNA) was measured in all patients and compared with clinical benefit.

Patients And Methods: Eligible patients had stage IIIB or IV NSCLC after 1 previous line of chemotherapy and an Eastern Cooperative Oncology Group performance status of 0 to 2.

Phase I study of PM00104 (Zalypsis®) administered as a 1-hour weekly infusion resting every fourth week in patients with advanced solid tumors.

PM00104 (Zalypsis®) is a new synthetic alkaloid with potent cytotoxic activity against tumor cell lines. This phase I clinical trial determined the maximal tolerated dose (MTD) and recommended dose (RD) for phase II trials of PM00104 administered as a 1-hour intravenous (i.v.

NAD(P)H:quinone oxidoreductase 1 and nrh:quinone oxidoreductase 2 activity and expression in bladder and ovarian cancer and lower NRH:quinone oxidoreductase 2 activity associated with an NQO2 exon 3 single-nucleotide polymorphism.

Purpose: NRH:quinone oxidoreductase 2 (NQO2) is a homologue of NAD(P)H:quinone oxidoreductase 1 (NQO1). Despite 54% homology with human NQO1, NQO2 has little endogenous enzymatic activity. However, NQO2 has potential as a therapeutic target because the addition of the nonbiogenic electron donor dihydronicotinamide riboside (NRH) selectively potentiates the bioactivation of the alkylating agent tretazicar (CB 1954).