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This article shows that ETX is not effective to treat neuropathic pain. Nevertheless, per-protocol analysis suggests a possible analgesic effect of ETX. Thus, our work adds significant knowledge to preclinical and clinical data on the benefits of T-type calcium channel inhibition for the treatment of neuropathic pain.

Nerve-sparing radical hysterectomy by robot-assisted laparoscopy is feasible in early cervical cancer (<2 cm). A total of 93.3 % of the patients were discharged 2 days after surgery with spontaneous voiding. The next step would be a prospective study with objective urodynamic investigations.

Background: Ziconotide is a new analgesic agent administered intrathecally. It is challenging to use and can induce several and sometimes serious adverse events. A low initial dosage followed by slow titration may reduce serious adverse events. Objective: To determine whether a low starting dosage of ziconotide, followed by slow titration, decreases the incidence of major adverse events associated with ziconotide when used for intractable cancer pain. Study Design: Observational cohort study. Setting: Three French cancer centers. Methods: Patients with incurable cancer causing chronic pain rated above 6/10 on a numerical scale while receiving high-dose opioid therapy (more than 200 mg/d of oral morphine equivalent) and/or exhibiting severe opioid-related adverse events received intrathecal infusions of ziconotide combined with morphine, ropivacaine, and clonidine. Results: Seventy-seven patients were included. Adverse events were recorded in 57% of them; moderate adverse events occurred in 51%. Adverse events required treatment discontinuation in 7 (9%) including 5 (6%) for whom a causal role for ziconotide was highly likely; among them 4 (5%) were serious. All patients experienced a significant and lasting decrease in pain intensity (by 48%) in response to intrathecal analgesic therapy that included ziconotide. Limitations: Limitations include the nonrandomized, observational nature of the study. Determining the relative contributions of each drug to adverse events was difficult, and some of the adverse events manifested as clinical symptoms of a subjective nature. Conclusions: The rates of minor and moderate adverse events were consistent with previous reports. However, the rate of serious adverse events was substantially lower. Our study confirms the efficacy of intrathecal analgesia with ziconotide for relieving refractory cancer pain. These results indicate that multimodal intrathecal analgesia in patients with cancer pain should include ziconotide from the outset in order to provide time for subsequent slow titration. Key words: Ziconotide, adverse events, intrathecal therapy, cancer pain, morphine, ropivacaine, clonidine.

Objective: This study reports the pharmacokinetics, tolerability, and safety of an intranasal fentanyl spray (INFS) in patients with cancer and breakthrough pain (BTP).Design: A randomized, open-label, two-period, crossover trial.Patients: Nineteen adult patients (mean 57.8 years) with BTP, receiving opioid treatment for chronic background pain, from clinical departments in Austria, France, and Norway entered and completed the study.Intervention: Patients were randomly assigned to receive one of six INFS dose sequences: 50/100, 100/50, 50/200, 200/50, 100/200, and 200/100 μg. INFS was administered as a single dose in one nostril. Each dose was separated by a minimum of 48 hours.Main outcome measure: Plasma fentanyl concentrations were measured by high-performance liquid chromatography and tandem mass spectrometry from blood samples obtained at 0 (predose) and frequently up to 300 minutes after INFS administration. Blood pressure, peripheral oxygen saturation, and respiratory rate were assessed eight times during each of the two treatment periods.Results: Mean fentanyl plasma concentrations increased in a dose-dependent manner, peaking for all fentanyl doses 9-15 minutes after INFS administration. Median Tmax values were 15, 12, and 15 minutes for the 50, 100, and 200 μg doses of INFS, respectively. Mean (SD) values for Cmax were 351 (±226), 595 (±400), and 1195 (±700) pg/mL, respectively, indicating dose-proportionality. Six patients (31.6 percent) experienced adverse events during the treatment period, the majority being mild in severity.Conclusion: INFS at doses of 50, 100, and 200 μg showed a short Tmax and was well tolerated in patients with cancer. These results support INFS use in patients with cancer suffering from BTP.

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