Treatment of recurrent malignant gliomas with fotemustine monotherapy: impact of dose and correlation with MGMT promoter methylation

<p>Abstract</p> <p>Background</p> <p>In recurrent malignant gliomas (MGs), a high rate of haematological toxicity is observed with the use of fotemustine at the conventional schedule (100 mg/m²weekly for 3 consecutive weeks followed by triweekly administration after a 5-week rest period). Also, the impact of O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status on fotemustine activity has never been explored in the clinical setting.</p> <p>Methods</p> <p>40 patients with recurrent pretreated MG were identified as being treated with fotemustine at doses ranging from 65 mg/m²to 100 mg/m². Patients were classified into 3 groups according to the dose of fotemustine received, from the lowest dosage received in group A, to the highest in group C. Analysis of MGMT promoter methylation in tumor tissue was successfully performed in 19 patients.</p> <p>Results</p> <p>Overall, 20% of patients responded to treatment, for a disease control rate (DCR, responses plus stabilizations) of 47.5%. Groups A and B experienced a response rate of 40% and 26.5% respectively, while the corresponding value for group C was 10%. Out of 19 patients, MGMT promoter was found methylated in 12 cases among which a DCR of 66.5% was observed. All 7 patients with unmethylated MGMT promoter were progressive to fotemustine.</p> <p>Conclusion</p> <p>Low-dose fotemustine at 65–75 mg/m²(induction phase) followed by 75–85 mg/m²(maintenance phase) has an activity comparable to that of the conventional schedule. By determination of the MGMT promoter methylation status patients might be identified who are more likely to benefit from fotemustine chemotherapy.</p

Issues related to the pharmacological management of patients with brain tumours and epilepsy

The patient affected by epilepsy related to brain tumours presents certain features linked to the summation of his cancer-related problems and his epilepsy-related problems. Furthermore, epilepsy in brain tumour patients is often refractory to pharmacological treatments and can complicate the therapeutic management of these patients due to the increased incidence of pharmacological interactions and adverse effects. Analysis of the data in the literature suggests that it is opportune, when planning antiepileptic therapy in these cases, to choose the new-generation drugs, as these show a lower incidence of pharmacological interactions with the therapies used in brain tumour patients (chemotherapies, radiotherapy and support therapies), have fewer adverse effects, and have less impact on neuropsychological functions, all factors that strongly influence the patient’s quality of life. Of the new antiepileptic drugs, the following seem to be promising in the treatment of cancer-related epilepsy: oxcarbazepine, topiramate and levetiracetam (the latter as an add-on therapy). The pharmacokinetic features of these drugs, their effectiveness in controlling seizures, and the reduced incidence of adverse effects make them useful in this particular group of patients

Sexual dysfunction following surgery for rectal cancer - a clinical and neurophysiological study

Abstract Background Sexual dysfunction following surgery for rectal cancer may be frequent and often severe. The aim of the present study is to evaluate the occurrence of this complication from both a clinical point of view and by means of neurophysiological tests. Methods We studied a group of 57 patients submitted to rectal resection for adenocarcinoma. All the patients underwent neurological, psychological and the following neurophysiological tests: sacral reflex (SR), pudendal somatosensory evoked potentials (PEPs), motor evoked potential (MEPs) and sympathetic skin responses (SSRs). The results were compared with a control group of 67 rectal cancer patients studied before surgery. Only 10 of these patients could be studied both pre- and postoperatively. 10 patients submitted to high dose preoperative chemoradiation were studied to evaluate the effect of this treatment on sexual function. Statistical analysis was performed by means of the two-tailed Student's t test for paired observations and k concordance test. Results 59.6% of patients operated reported sexual dysfunction, while this symptom occurred in 16.4% in the control group. Moreover, a significantly higher rate of alterations of the neurophysiological tests and longer mean latencies of the SR, PEPs, MEPs and SSRs were observed in the patients who had undergone resection. In the 10 patients studied both pre and post-surgery impotence occurred in 6 of them and the mean latencies of SSRs were longer after operation. In the 10 patients studied pre and post chemoradiation impotence occurred in 1 patient only, showing the mild effect of these treatments on sexual function. Conclusion Patients operated showed severe sexual dysfunctions. The neurophysiological test may be a useful tool to investigate this complication. The neurological damage could be monitored to decide the rehabilitation strategy.</p