Sorafenib for the Treatment of Advanced Hepatocellular Cancer - a UK Audit.

AIMS: Sorafenib is the current standard treatment for advanced hepatocellular carcinoma. We carried out a national audit of UK patients treated with sorafenib as standard-of-care and those treated with systemic therapy in first-line trials. MATERIALS AND METHODS: Sorafenib-treated and trial-treated patients were identified via the Cancer Drugs Fund and local databases. Data were collected retrospectively from medical records according to a standard case report form. The primary outcome measure was overall survival, estimated by the Kaplan-Meier method. RESULTS: Data were obtained for 448 sorafenib-treated patients from 15 hospitals. The median age was 68 years (range 17-89) and 75% had performance status ≤ 1. At baseline, 77% were Child-Pugh A and 16.1% Child-Pugh B; 38% were albumin-bilirubin grade 1 (ALBI-1) and 48% ALBI-2; 23% were Barcelona Clinic Liver Classification B (BCLC-B) and 72% BCLC-C. The median time on sorafenib was 3.6 months, with a mean daily dose of 590 mg. The median overall survival for 448 evaluable sorafenib-treated patients was 8.5 months. There were significant differences in overall survival comparing Child-Pugh A versus Child-Pugh B (9.5 versus 4.6 months), ALBI-1 versus ALBI-2 (12.9 versus 5.9 months) and BCLC-B versus BCLC-C (13.0 versus 8.3 months). For trial-treated patients (n=109), the median overall survival was 8.1 months and this was not significantly different from the sorafenib-treated patients. CONCLUSION: For Child-Pugh A patients with good performance status, survival outcomes were similar to those reported in global randomised controlled trials. Patients with ALBI grade > 1, Child-Pugh B or poor performance status seem to derive limited benefit from sorafenib treatment.

PO-39 - Primary thromboprophylaxis for ambulatory patients with advanced metastatic pancreatic cancer. A practical implementation of lessons from published experience.

INTRODUCTION: The efficacy and safety of primary prophylaxis in advanced pancreatic cancer (APC) has been demonstrated in randomized controlled studies. Current guidelines suggest use of primary prophylaxis in high risk ambulatory cancer patients. The VTE in cancer working group in our centre reviewed our experience with FRAGEM and relevant literature. OBSERVATIONS: (1) Dose: (a) conventional prophylactic dosing is not established in APC (b) 200IU/kg followed by 150IU/kg dalteparin may be superior to 1mg/kg followed by 40mg enoxaparin. (2) Duration of treatment: (a) FRAGEM observed a rapid increase in VTE events after the 3-month treatment period. Transfer to 40mg enoxaparin in CONKO-04 after 3months also demonstrated reduced efficacy. (3) Recognition that bleeding in metastatic incurable pancreatic cancer is not uncommon even without anticoagulation. Cumulative incidence rates of major bleeding over the first 3months were: 4.5% vs. 3.4% (NS) in CONKO-04 and 3.4% vs. 3.1 % (NS) in FRAGEM (treatment vs observation arms respectively). AIM: This abstract describes our interpretation and experience on implementing available evidence for primary prophylaxis in ambulatory APC patients. MATERIALS AND METHODS: A simplified body weight-adjusted schedule for thromboprophylaxis with Dalteparin for the ambulant APC patient was agreed as follows: <50kg: 7500IU, 50 -80kg: 10,000IU, >80kg: 12,500IU. Eligible patients: All patients with advanced / metastatic pancreatic cancer undergoing palliative chemotherapy. Dalteparin treatment was initiated at least one day prior to the first administration of chemotherapy and continued until death or unacceptable toxicity (bleeding). This guideline was implemented in May 2009. A departmental audit was conducted for patients treated till December 2012 to assess efficacy and safety. RESULTS: Results of the audit have been presented in an analysis including 67 patients. The compound adverse outcome (CAE) in this cohort was 24% (VTE: 13%, bleeding: 11%). For patients with no prior exposure to anticoagulation CAE rate was 18% (VTE: 7%, bleeding: 11%) with a median duration of LMWH treatment of 8months. The majority of the bleeding events observed were due to cancer related lesions (duodenal infiltration or varices). VTE and bleeding rates were similar to published experience with extended duration therapeutic LMWH in cancer-related VTE. VTE risk appeared improved compared to the 3-month regimen of FRAGEM. CONCLUSIONS: In our opinion, thromboprophylaxis in ambulatory APC is a pragmatic evidence-based approach trying to deal with a serious cancer related complication that affects these patients. It is expected that data from further randomised trials (e.g SELECT-D and CASSINI) will provide further evidence in this area.

Ethno-Medical Plants and Methods Used by Gwandara Tribe of Sabo Wuse in Niger State; Nigeria; to Treat Mental Illness

The Gwandara people of Sabo Wuse in Niger State; Nigeria are the original inhabitants of Wuse in Abuja Municipal Area Council. They were resettled at this present location of Sabo Wuse from Wuse in the Federal Capital Territory Abuja when the seat of government moved from Lagos to Abuja 30 years ago. Sabo Wuse still remains relatively a remote settlement and their lifestyle unchanged. They still depend to a large extent on their traditional knowledge of medicinal plants to treat ailments. Ethnobotanical survey was conducted to identify and document methods traditionally utilized for treatment of mental illness and to expand the quality and quantity of information for research and development especially in the area of new drug discovery and development. About sixty seven (67) Traditional Medicine Practitioners were interviewed orally with use of questionnaire. From our survey; various methods were found to be used by the traditional medicine practitioners to treat mental illness and associated disorders. These include music; incantations and medicinal plants in various formulations - decoction; powder; infusion - which are administered in various ways like fumigation; inhalation; bathing; steaming and drinking. Eighteen plant species belonging to twelve different families were documented to be included in these therapies. In conclusion; there is an array of plants used locally to treat mental illness and it is recommended that such surveys should be funded and leads for drugs to treat mental illness obtained from such; at the same time documenting our indigenous knowledge

Ethno-medicinal plants and methods used by Gwandara tribe of Sabo Wuse in Niger State, Nigeria, to treat mental illness.

The Gwandara people of Sabo Wuse in Niger State, Nigeria are the original inhabitants of Wuse in Abuja Municipal Area Council. They were resettled at this present location of Sabo Wuse from Wuse in the Federal Capital Territory Abuja when the seat of government moved from Lagos to Abuja 30 years ago. Sabo Wuse still remains relatively a remote settlement and their lifestyle unchanged. They still depend to a large extent on their traditional knowledge of medicinal plants to treat ailments. Ethnobotanical survey was conducted to identify and document methods traditionally utilized for treatment of mental illness and to expand the quality and quantity of information for research and development especially in the area of new drug discovery and development. About sixty seven (67) Traditional Medicine Practitioners were interviewed orally with use of questionnaire. From our survey, various methods were found to be used by the traditional medicine practitioners to treat mental illness and associated disorders. These include music, incantations and medicinal plants in various formulations--decoction, powder, infusion--which are administered in various ways like fumigation, inhalation, bathing, steaming and drinking. Eighteen plant species belonging to twelve different families were documented to be included in these therapies. In conclusion, there is an array of plants used locally to treat mental illness and it is recommended that such surveys should be funded and leads for drugs to treat mental illness obtained from such, at the same time documenting our indigenous knowledge.

Neuropharmacological screening of Diospyros mespiliformis in mice.

The neuropharmacological activities of the aqueous extract of Diospyros mespiliformis stem bark were screened in mice. The extracts effect on pentobarbital-induced sleeping time, pentylenetetrazole induced seizure, spontaneous motor activity (SMA), exploratory behaviour, and rota-rod performance (motor coordination) were evaluated. The extract (100 and 200 mg/kg p.o.) produced a significant (P<0.05) prolongation of pentobarbital-induced sleeping time, and reduced the SMA and exploratory behaviour. The extract prolonged onset of the phases of seizure activity but did not protect mice against lethality induced by pentylenetetrazole. It also failed to affect the motor coordination test. These results suggest that the extract contained an agent with neuropharmacological activity that may be sedative in nature.

Pharmacological evidence favouring the folkloric use of Diospyros mespiliformis Hochst in the relief of pain and fever.

The methanol extract of Diospyros mespiliformis was evaluated for its claimed folkloric usage in the relief of pain and fever. Antipyretic, analgesic and anti-inflammatory effects of the extract were evaluated in rats and mice. Studies were carried out on yeast-induced pyrexia in rats, acetic acid-induced writhing in mice, formalin test and egg albumin-induced anti-inflammatory activity in rats. The extract (50 and 100 mg/kg i.p.) gave a potent antipyretic effect for 100 mg/kg and significant activity (P<0.05) against all the analgesic and anti-inflammatory models used. The LD(50) of the extract was estimated to be 513.80+/-33.92 mg/kg i.p. in mice. These results provide support for the use of the plant in relieving pain and fever.