A multicenter phase II trial of intrathecal topotecan in patients with meningeal malignancies.

To determine the therapeutic efficacy (13-week and 26-week CNS progression-free survival [PFS], response rate, and overall survival) and safety of intraventricular (IVent) topotecan in patients with neoplastic meningitis (NM), we conducted a phase II, open-label, nonrandomized, single-arm trial of IVent topotecan in patients with NM using 400 mug of topotecan IVent twice weekly for 6 weeks, followed by evaluation with imaging, cerebrospinal fluid (CSF), and physical examinations. In the absence of disease progression, patients were then treated with IVent topotecan weekly for 6 weeks, twice monthly for 4 months, and monthly thereafter. Sixty-two patients (23 males and 39 females) were enrolled from April 2001 through March 2006. Median age and KPS at enrollment were 56 (range 5-83) and 80 (range 60-100), respectively. Primary cancers included breast (19), lung (13), CNS (14), and others (16). Forty patients (65%) completed the 6-week induction period, among whom 13 (21%) had CSF clearance of malignant cells. Kaplan-Meier estimates of PFS at 13 and 26 weeks were 30% (95% confidence interval [CI], 20%-45%) and 19% (95% CI, 11%-34%). Overall median survival (50 deaths) was 15 weeks (95% CI, 13-24 weeks). The most common side effect was chemical meningitis in 32% of patients (5% grade 3); 32% experienced no drug side effects. IVent topotecan is well tolerated, but provides no added benefit over other IVent therapies. Because of its modest side effect profile, combining IVent topotecan with other IVent or systemic interventions should be considered.

Seizures and epilepsy in cancer: etiologies, evaluation, and management.

Seizure and epilepsy are common neurologic issues in cancer patients. Etiologies include structural abnormalities of the brain (eg, brain metastasis), cerebrovascular disease, reversible posterior leukoencephalopathy syndrome (RPLS), and radiation toxicity. Seizures associated with these etiologies often have focal features. Metabolic causes include hypoglycemia, electrolyte abnormalities, tumor lysis syndrome, thrombotic thrombocytopenic purpura (TTP), and medications used in cancer. A careful clinical evaluation can suggest the seizure etiology and guide subsequent work-up. Nonconvulsive status epilepticus should be suspected with persistent decreased level of consciousness following a seizure. Certain etiologies, such as RPLS and TTP, must be treated aggressively to minimize permanent neurologic injury. Routine prophylaxis with antiepileptic drugs (AEDs) is not recommended in patients with primary brain tumors or brain metastasis who have never had a seizure. Where indicated, the selection of AEDs should take into consideration side effects and interactions with chemotherapy. For this reason, non-enzyme-inducing AEDs are preferable in the cancer setting.

Neoplastic meningitis in patients with adenocarcinoma of the gastrointestinal tract.

BACKGROUND: Neoplastic meningitis (NM) occurs in 5-10% of patients with malignant disease. Little is known about the outcomes of patients with gastrointestinal (GI) malignancies who develop NM. For this report, the authors characterized the clinical course and attempted to identify prognostic factors in patients with NM due to primary malignancies of the GI tract. METHODS: In this retrospective study, 21 patients with GI primary tumors and NM were identified: Their medical records and imaging studies were reviewed. RESULTS: The patient population was composed of patients with gastric adenocarcinoma (n = 8 patients), esophageal adenocarcinoma (n = 7 patients), colon and/or rectal adenocarcinoma (n = 5 patients), and pancreatic adenocarcinoma (n = 1 patient). The median overall survival after the initial diagnosis of adenocarcinoma was 55 weeks (range, 8-884 wks), and the median survival after the diagnosis of NM was 7 weeks (range, 0-64 wks). Four patients died during palliative radiotherapy. No factors identified had an impact on outcome, including symptoms, physical findings at diagnosis, imaging characteristics, or cerebrospinal fluid findings. Univariate analysis showed a trend toward better outcomes for patients who received any kind of treatment directed toward the NM. CONCLUSIONS: Patients with NM from GI tract adenocarcinomas universally had poor outcomes. Until NM can be diagnosed earlier and/or until more effective therapies are identified, comfort care alone may be a reasonable alternative for some of these unfortunate patients.

Peripheral neuropathy and cancer.

Peripheral neuropathy has a major impact on quality of life and may limit the amount of treatment patients can receive. Neurotoxic agents are used increasingly in oncologic practice, yet clinicians are often unaware of the protean manifestations of neuropathy and find its management troubling. Recent knowledge about the mechanisms of neuropathic disease and new treatments may help to minimize the impact of neuropathy on this vulnerable patient population.

Tacrolimus-associated posterior reversible encephalopathy syndrome after allogeneic haematopoietic stem cell transplantation.

Neurotoxicity is a significant complication of the use of tacrolimus. From April 1998 to December 2001, we identified 10 patients (six women, four men) who developed 11 episodes of tacrolimus-associated posterior reversible encephalopathy syndrome (PRES) after allogeneic haematopoietic stem cell transplantation for haematological malignancies. The diagnosis was made by characteristic clinical findings (mental status changes, seizures, neurological deficits) with the exclusion of other causes and characteristic imaging findings. The median age was 35.5 years (range 19-57 years). Seven patients received a matched-unrelated donor transplant and three received a cord blood transplant. The overall incidence of PRES was 1.6%, while the incidence in matched-unrelated, mismatched-related and cord blood transplants was 3.5%, 4.9% and 7.1% respectively. Mental status changes, cognitive deficits, seizures and lethargy were the most common clinical findings. Eight of 10 patients had characteristic findings of hyperintensity of the white matter on T2-weighted images and FLAIR (fluid-attenuated inversion recovery) sequence on magnetic resonance imaging of the brain. Serum tacrolimus levels were within the therapeutic range in most patients. Tacrolimus treatment was continued (n = 4) or temporarily withheld (n = 7) for 1-14 d. One patient was changed to cyclosporine. In most patients, subsequent treatment with tacrolimus was well tolerated without recurrence of neurotoxicity.