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125 Background: Phase III studies have demonstrated survival benefits from abiraterone (Abi), and enzalutamide (Enz) following disease progression in metastatic castrate resistant prostate cancer (mCRPC). Abi is now available for treatment of mCRPC in the UK in patients previously treated with docetaxel. Enz has recently become available, via the UK cancer drugs fund (CDF), for progressive disease post docetaxel, prior to exposure to Abi. There has been no randomised trial on sequential usage of Enz post-Abi. We therefore, report the experience of hospitals in Coventry, Cardiff, and five centers in Birmingham. Methods: We searched the pharmacy database for patients who have received Enz as part of an early access scheme, and identified 79 patients who started treatment between the August 2012 and April 2013. A detailed notes review was carried out of these patients. Results: Median age was 74 (range of 55 to 87). All patients had received hormone androgen deprivation therapy and taxane chemotherapy (docetaxel and/or cabazitaxel) 75 patients had received previous Abi, 62 of these patients receiving Abi as the last treatment prior to Enz. The mean time to progression (TTP) for Abi in these 62 patients was 37.44 weeks (range 4 to 104). At the time of submission 55 patients had stopped Enz due to prostate-specific antigen progression with a mean TTP of 15.87 weeks and 28 patients had died. Conclusions: The AFFIRM study demonstrated TTP of 36 weeks in patients post-docetaxel. In this audit of patients receiving Enz post-Abi the TTP was only 15.87 weeks, suggesting possible reduced efficacy in patients receiving Enz post-Abi and docetaxel. Trials are underway comparing Abi alone or in combination with Enz which may improve efficacy.

ABSTRACT. Thymomas are the most common tumours of the anterior mediastinum; their clinical course is often complicated by accompanying autoimmune and paraneoplastic syndromes. Advanced malignant thymoma is particularly challenging to manage owing to the lack of evidence from randomised trials to guide treatment. Combination first-line chemotherapy has been trialled in several small studies and has been reported to produce a 50-80% response with platinum-containing regimes. Progression following first-line chemotherapy is difficult to manage as most of these patients maintain a good performance status and demand further active palliative treatment. There is no standard second-line treatment. We report a good clinical and radiological response to third-line palliative octreotide therapy in a patient who had a positive octreotide scan.

Abstract. In response to increasing pressure on inpatient services and a meta-analysis indicating that cisplatin (C) is superior to carboplatin, we report a phase II trial of gemcitabine (G) and split-dose C in advanced non-small cell lung cancer (NSCLC) in an outpatient setting. Patients with stage IIIB/IV NSCLC received: G/C 1250/40 mg/m 2 ; G and C were given on day (d) 1 and d8 in a 21d cycle. Patients with performance status 0-2, adequate bone marrow function and calculated glomerular filtration rate (GFR) >50 ml/min were eligible. Forty-two patients were enrolled: 25 male; median age 62 (range 37-78) years. There were 26 patients (62%) with stage IV disease. One hundred and thirty-eight cycles of chemotherapy were delivered. Chemotherapy was well tolerated, allowing maintenance of planned dose intensity (DI) with mean dose delivered of 780.1 mg/m 2 (93%) and 25.6 mg/m 2 (96%) for G and C, respectively. The overall response rate was 43%. Median survival was 12.5 months with a median follow-up of 13.5 months. One year survival rate was 51%. G plus C both given on d1 and d8 (q21d) is a very active, well tolerated and convenient outpatient schedule, which maintains DI. IntroductionPlatinum-based chemotherapy is used for most patients with advanced NSCLC and is superior to best supportive care alone in terms of survival and quality of life (1,2). Gemcitabine plus carboplatin (GCb) is the most widely used regimen in the UK (3). Outpatient administration of GCb is considered more convenient than cisplatin-based regimens that require admission or protracted outpatient visits for hydration and diuresis. Doubt remains over the relative efficacy of carboplatin (Cb) and cisplatin (C) when given in combination with newer chemotherapeutic agents. Several studies making this comparison show superiority for cisplatin over carboplatin (4-7). Furthermore, a meta-analysis of randomised trials comparing cisplatin to carboplatin has indicated a significant survival advantage favouring cisplatin when combined with a new agent (8).It has been reported that the optimal dose intensity of cisplatin for NSCLC is between 21-30 mg/m 2 /week, equating to either 70-80 mg/m 2 q 3-weekly or 100 mg/m 2 q 4-weekly (Raftopoulos H, et al, Proc ASCO 22: abs. 2596. Administration of a cisplatin dose of this magnitude requires an 8-h schedule. Such a regimen poses practical difficulties for chemotherapy outpatient departments and the cost of inpatient care can be prohibitive. An out-patient splitdose gemcitabine plus cisplatin regimen involving two 4-h visits may circumvent these issues and facilitate the use of the more active platinum agent without compromising dose intensity.Experimental data suggest that a combination of gemcitabine and cisplatin given using an appropriate schedule (simultaneous or close proximity exposure) can act synergistically. Synergy may be mediated by inhibition of ribonucleotide reductase by gemcitabine depleting the deoxynucleotide pool required for DNA replication and thereby inhibiting excision repair of cisplatin...

IntroductionThe management of locally advanced inoperable malignant thymoma is difficult as there are no large randomized clinical trial data to guide treatment. However various case series have shown that malignant thymoma is often a chemosensitive disease. Cisplatin-based chemotherapy has been the gold-standard in the management of these patients. However when thymic cancers are complicated by paraneoplastic syndromes that damage kidney and neurological function, cisplatin use is often contraindicated.Case presentationWe report a case of a 37 year old man with locally advanced malignant thymoma complicated by significant nephrotic syndrome and renal impairment. He responded to a novel combination of carboplatin, epirubicin and cyclophosphamide chemotherapy used as first line therapy.ConclusionThe treatment with chemotherapy of locally advanced malignant thymoma complicated by nephrotic syndrome and renal impairment is difficult due to the increase of toxicity. In this case, a novel chemotherapy combination with lesser toxicity was used successfully. In addition this chemotherapy combination did not impede the later use of conventional cisplatin-based chemotherapy. Therefore we suggest a course of carboplatin-based chemotherapy for locally advanced malignant thymoma in patients who are unsuitable for cisplatin.

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