Preliminary assessment of a neuropathic pain treatment and referral algorithm for patients with cancer.

CONTEXT: The purpose of this case series study was to pilot test an evidence-based neuropathic pain (NP) treatment and referral algorithm for use by oncology nurses when managing cancer-related NP. OBJECTIVES: The primary study objective was to assess patient-reported outcomes (pain severity, changes in activities of daily living, and satisfaction) resulting from algorithm use. METHODS: Outpatients (n=20) with cancer-related NP scores ≥4 on a 0-10 numeric rating scale participated in the study. NP assessment, treatment, and referral to ancillary providers were guided by an evidence-based NP algorithm that was implemented by oncology nurse practitioners. Based on efficacy evidenced through randomized clinical trials published at the time of study implementation, the following drugs were included in the algorithm: lidocaine patch, gabapentin, oxycodone, tramadol, morphine, methadone, duloxetine, pregabalin, and nortriptyline. Recommendations for starting dose, dose escalation, drug combinations, treatment duration, and contraindications were included for first-tier drugs. Patient-reported outcomes (pain severity, functional capacity, and satisfaction) were assessed monthly over 12 weeks. RESULTS: Average NP severity (P=0.001), general activity (P<0.001), mood (P=0.002), walking ability (P=0.01), ability to perform normal work (P=0.002), relationships (P=0.002), sleep (P=0.01), life enjoyment (P<0.001), and patient satisfaction (P=0.003) all improved by 12 weeks. CONCLUSION: Evidence from this pilot study suggests that NP evidence-based treatment may result in improved symptoms, function, and patient satisfaction. A randomized controlled trial is needed to further assess algorithm efficacy.

Efficacy of thalidomide for the treatment of amyotrophic lateral sclerosis: a phase II open label clinical trial.

Neuroinflammation through the cytokine, tumor necrosis factor-alpha (TNF-alpha) is thought to play an important role in the pathogenesis of amyotrophic lateral sclerosis (ALS). We conducted a preliminary phase II trial of thalidomide, which reduces levels of TNF-alpha pre-transcriptionally and post-transcriptionally in vivo and has been shown to prolong disease duration and extend the lifespan of transgenic animal models of ALS. Patients who met diagnostic criteria for ALS received thalidomide at escalating doses to a target dose of 400 mg/day. The primary endpoints in the trial were the ALS Functional Rating Scale (ALSFRS) and pulmonary function testing (PFT) curves after nine months of thalidomide treatment that were compared to historical controls. Secondary endpoints were: survival stratified for newly diagnosed and progressive disease, toxicity, quality of life, and serum cytokine measurements. Twenty-three patients were enrolled, but only 18 were evaluable for the primary outcome. There was no improvement in the ALSFRS or PFT compared to historical controls. Thalidomide had several side-effects in our ALS patients. There was no significant shift in cytokine profile after treatment compared to baseline. In conclusion, treatment of ALS with the TNF-alpha inhibitor, thalidomide, does not appear to effectively modulate disease progression and can cause adverse effects.

A phase II study of thalidomide and irinotecan for treatment of glioblastoma multiforme.

PURPOSE: Irinotecan is a cytotoxic agent with activity against gliomas. Thalidomide, an antiangiogenic agent, may play a role in the treatment of glioblastoma multiforme (GBM). To evaluate the combination of thalidomide and irinotecan, we conducted a phase II trial in adults with newly-diagnosed or recurrent GBM. PATIENTS AND METHODS: Thalidomide was given at a dose of 100 mg/day, followed by dose escalation every 2 weeks by 100 mg/day to a target of 400 mg/day. Irinotecan was administered on day 1 of each 3 week cycle. Irinotecan dose was 700 mg/m(2) for patients taking enzyme-inducing anticonvulsants and 350 mg/m(2) for all others. The primary endpoint was tumor response, assessed by MRI. Secondary endpoints were toxicity, progression-free survival, and overall survival. RESULTS: Twenty-six patients with a median age of 55 years were enrolled, with fourteen evaluable for the primary outcome, although all patients were included for secondary endpoints. One patient (7%) exhibited a partial response after twelve cycles, and eleven patients (79%) had stable disease. The intention to treat group with recurrent disease included 16 patients who had a 6-month PFS of 19% (95% CI: 4-46%) and with newly-diagnosed disease included 10 patients who had a 6-month PFS of 40% (95% CI: 12-74%). Gastrointestinal (GI) toxicity was mild, but six patients (23%) experienced a venous thromboembolic complication. Two patients had Grade 4 treatment-related serious adverse events that required hospitalization. There were no treatment-related deaths. CONCLUSION: The combination of irinotecan and thalidomide has limited activity against GBM. Mild GI toxicity was observed, but venous thromboembolic complications were common.

Long-term response of pituitary carcinoma to temozolomide. Report of two cases.

Pituitary carcinoma is a rare tumor characterized by poor responsiveness to therapy, leading to early death. Reported responses to standard chemotherapy have only been anecdotal, with no single agent or combination demonstrating consistent efficacy in the treatment of patients with this disease. The authors report rare examples of a persistent response to cytotoxic chemotherapy in two patients with pituitary carcinoma. One patient was a 38-year-old man with visual field loss caused by a luteinizing hormone-secreting pituitary carcinoma that had recurred despite multiple surgeries and radiation therapy. Intradural metastases to the spine that had failed to respond to radiation therapy were pathologically confirmed. The second patient was a 26-year-old man with hyperprolactinemia from a prolactin-secreting pituitary tumor. Spine magnetic resonance images obtained to search for causes of neck pain showed a vertebral tumor, which was later confirmed through pathological analysis to be a metastatic pituitary carcinoma. His disease progressed despite radiation therapy, high-dose bromocriptine, and chemotherapy. Both patients were treated monthly with temozolomide, which was administered orally on the first 5 days of a 28-day cycle. The patient in the first case underwent all 12 treatment cycles without serious side effects, and his visual field deficits improved. The patient in the second case had undergone only 10 cycles when the drug was stopped because of his severe fatigue. Nonetheless, his pain disappeared and his serum prolactin concentration decreased. Both patients continue to have partial responses and have been employed full-time for more than 1 year after discontinuing temozolomide therapy. These two examples demonstrate that temozolomide may be effective in treating pituitary carcinomas and thus should be considered in the treatment algorithm for these difficult cases.

A Phase II trial of paclitaxel and topotecan with filgrastim in patients with recurrent or refractory glioblastoma multiforme or anaplastic astrocytoma.

PURPOSE: Therapy for high-grade gliomas remains unsatisfactory. Paclitaxel and topotecan have separately demonstrated activity against gliomas. We conducted a Phase II trial of these agents in combination with filgrastim (G-CSF) in patients with recurrent or refractory glioblastoma multiforme or anaplastic astrocytoma. PATIENTS AND METHODS: Adult patients with radiographic evidence of recurrent or progressive tumor following primary therapy were eligible for study. Patients received paclitaxel 175 mg/m2 IV over 3 h on day 1 and topotecan 1.0 mg/m2 IV over 30 min on days 1-5. Filgrastim 5 microg/kg was given days 6-14 for neutrophil support. Treatment cycles were repeated every 21 days. RESULTS: Twenty patients were enrolled on study, and seventeen were considered evaluable for response. Two patients (12/%) exhibited partial remission and seven patients (41/%) exhibited stable disease in response to therapy. Hematologic toxicity was common with 25 /% of patients experiencing grade III or IV leukopenia despite G-CSF support. Two patients died of infectious complications on protocol, prompting suspension of further accrual. CONCLUSION: Paclitaxel and topotecan with G-CSF support exhibits modest activity in adults with recurrent or refractory glioblastoma and anaplastic astrocytoma. The significant hematotoxicity encountered, however, cannot justify further investigation of this combination in patients with high grade brain tumors.