GEINOFOTE: efficacy and safety of fotemustine in patients with high-grade recurrent gliomas and poor performance status

Purpose: The treatment of recurrent high-grade gliomas (HGG) is controversial. There are different therapeutic schedules but without a clear orientation about which of them should be used in each clinical situation. In addition, when patients suffer a second recurrence or they have poor performance status, they are excluded from clinical trials, although second recurrences and poor performance status are indeed more and more real and common situations in the clinical setting. In this study, we assessed the efficacy and safety of fotemustine (FTM) in HGG [fundamentally, glioblastomas (GB)], independent of time of recurrence or performance status. Methods/patients: Retrospective study in HGG patients treated with FTM in second or further line according to standard, the Addeo or any other scheme, starting treatment prior to 30 November 2012. Included patients reflect the regular situation in which the drug is used in terms of comorbidities and analytic situation (hematologic, renal and hepatic functions). Response assessment was performed by MRI and according to the clinical protocols of each center (every 8-12 weeks). Clinical situation and supportive care drugs were evaluated in each medical consultation. Clinical end-points analyzed, among others, were: PFS-6, PFS, OS, response rates, toxicity, quality of life and neurocognitive impact. Results: In terms of activity, an overall response rate of 8 % was observed: partial response 6 % (7 patients) and complete response 2 % (2 patients). The median time to achieve the greater response with FTM was 73 days (4-841 days). Patients treated according to the Addeo schedule had a shorter time to greater response in comparison with other schedules (85.9 vs 114 days), although without statistical significance. There were no significant differences in progression-free survival (PFS) when comparing different FTM schedules or using FTM in first or second recurrence. Median PFS: 3 months. PFS-6: 30.3 %. Overall survival (OS): although without significant differences, a tendency to better survival when using the Addeo schedule versus other schedules was observed (at 6 months, 44.6 vs 34.5 %; at 12 months, 25 vs 23.6 %; at 18 months, 11.5 vs 7.9 %), as well as if earlier use (second vs third line) concerning OS-12 (33.7 vs 18.2 %). Median OS: 5.2 months. Grades 3-4 toxicity was 28 % (31 patients), being neutropenia (4 %) and thrombocytopenia (17 %) the most frequent adverse reactions. From quality of life and neuro-cognitive function perspectives, 11 patients (10 %) and 16 (14 %) improved the Karnofsky Index and neurological impairment, respectively, after FTM treatment. Conclusion: This study has shown that FTM is safe and has a comparable activity with other available therapeutic options of use in the treatment of recurrent HGG (AU)

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Should we continue temozolomide beyond six cycles in the adjuvant treatment of glioblastoma without an evidence of clinical benefit? A cost analysis based on prescribing patterns in Spain

PURPOSE: The standard adjuvant treatment for glioblastoma is temozolomide concomitant with radiotherapy, followed by a further six cycles of temozolomide. However, due to the lack of empirical evidence and international consensus regarding the optimal duration of temozolomide treatment, it is often extended to 12 or more cycles, even in the absence of residual disease. No clinical trial has shown clear evidence of clinical benefit of this extended treatment. We have explored the economic impact of this practice in Spain. MATERIALS AND METHODS: Spanish neuro-oncologists completed a questionnaire on the clinical management of glioblastomas in their centers. Based on their responses and on available clinical and demographic data, we estimated the number of patients who receive more than six cycles of temozolomide and calculated the cost of this extended treatment. RESULTS: Temozolomide treatment is continued for more than six cycles by 80.5 % of neuro-oncologists: 44.4 % only if there is residual disease; 27.8 % for 12 cycles even in the absence of residual disease; and 8.3 % until progression. Thus, 292 patients annually will continue treatment beyond six cycles in spite of a lack of clear evidence of clinical benefit. Temozolomide is covered by the National Health Insurance System, and the additional economic burden to society of this extended treatment is nearly 1.5 million euros a year. CONCLUSIONS: The optimal duration of adjuvant temozolomide treatment merits investigation in a clinical trial due to the economic consequences of prolonged treatment without evidence of greater patient benefit (AU)

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Is capecitabine a new choice of treatment for lung adenocarcinoma? A case report involving partial response in second line of treatment and hypothesis of the biological basis.

In lung cancer different histologies have different biologies. Active agents in non-small-cell lung cancer (NSCLC) include platinums, paclitaxel, docetaxel, gemcitabine, erlotinib, pemetrexed and vinorelbine. We report a case of a patient with metastatic lung adenocarcinoma with high levels of LDH and CEA with clear partial response to capecitabine after several lines of chemotherapy. The increase in thymidine phosphorylase (TP) expression in NSCLC could provide a rationale for the use of capecitabine in this tumour. More research is needed to try to explain the striking activity of capecitabine in this patient with lung adenocarcinoma and high levels of CEA and to find molecular targets to predict the response to this agent.

Is capecitabine a new choice of treatment for lung adenocarcinoma? A case report involving partial response in second line of treatment and hypothesis of the biological basis

In lung cancer different histologies have different biologies. Active agents in non-small-cell lung cancer (NSCLC) include platinums, paclitaxel, docetaxel, gemcitabine, erlotinib, pemetrexed and vinorelbine. We report a case of a patient with metastatic lung adenocarcinoma with high levels of LDH and CEA with clear partial response to capecitabine after several lines of chemotherapy. The increase in thymidine phosphorylase (TP) expression in NSCLC could provide a rationale for the use of capecitabine in this tumour. More research is needed to try to explain the striking activity of capecitabine in this patient with lung adenocarcinoma and high levels of CEA and to find molecular targets to predict the response to this agent (AU)

Long-term outcome of a phase II study of weekly docetaxel with a short course of estramustine and enoxaparine in hormone-resistant prostate cancer patients

OBJECTIVE: The objective was to define the toxicity and activity of weekly docetaxel administered with a short course of estramustine and enoxaparine in patients with hormone-resistant prostate cancer (HRPC). PATIENTS AND METHODS: Twenty-four patients were treated with the next regimen: weekly docetaxel 36 mg/m(2) iv for three consecutive weeks every 28 days, and estramustine 280 mg three times a day for three consecutive days beginning the day before docetaxel (days 1-3, 8-10 and 15-17). In order to prevent thromboembolic events, 40 mg of subcutaneous enoxaparine was administered daily sc on the same days as estramustine. Primary endpoints were: toxicity, especially the presence of thromboembolic events, PSA response rate and response in measurable disease. Secondary endpoints were: time to PSA progression and overall survival. RESULTS: Nineteen of 24 patients (79.1%, 95% CI 71-87%) had a PSA response = or >50%. Four of the eleven patients with measurable disease had a partial response. The median time to PSA progression was 7 months (CI 95%: 6.5-9) and the median survival was 19 months (IC 95%: 11-24). Toxicity was manageable with no treatment- related mortality. Only two patients had grade 4 neutropenia. Two patients had thrombotic events, one deep venous thrombosis and one stroke. The main grade 3 non-haematologic toxicity was diarrhoea and asthenia, both in 25% of patients. CONCLUSIONS: Weekly docetaxel with a short course of estramustine and enoxaparine is active and tolerable in HRPC patients. The observed incidence of thrombosis was lower than previously reported but the association of enoxaparine was not enough to completely prevent the thromboembolic events (AU)

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Segundas líneas en cáncer de ovario ¿hay un estándar? / No disponible

La recaída del cáncer de ovario es habitualmente incurable y el tratamiento se basa en el empleo dequimioterapia paliativa. En pacientes con recaídas consideradas platinosensibles (más de 6 meses trasla última dosis de platino) existe suficiente evidencia científica para recomendar una combinación dequimioterapia basada en carboplatino, pues se ha demostrado un impacto en la supervivencia. Por elcontrario, en las pacientes con progresión a platino (refractarias) o con recaídas antes de 6 meses (resistentes)el tratamiento recomendado es la monoterapia secuencial con los fármacos activos en segundalínea. La ausencia de tratamiento estándar en este contexto hace que la elección se deba basar encriterios de toxicidad, calidad de vida y preferencia de la paciente