Ease of use of two autoinjectors in patients with multiple sclerosis treated with interferon beta-1a subcutaneously three times weekly: results of the randomized,crossover REDEFINE study

Background: For interferon beta-1a subcutaneously three times weekly (IFN β-1a SC tiw), administration options include manually injected prefilled syringes; a preassembled, single-use autoinjector; and a reusable autoinjector. This study evaluated patient-perceived ease of use of two injection devices.

Research design and methods: REDEFINE, a Phase IV, multicenter crossover study, randomized patients with multiple sclerosis and ≥5 weeks’ IFN β-1a 44 μg SC tiw use to 4 weeks using a single-use autoinjector, then 4 weeks using a reusable autoinjector, or vice versa. The primary endpoint was the proportion rating each ‘easy’ or ‘very easy’, with/without regard to previous device experience.

Results: Of 97 randomized patients, 29 had most recent experience with manual injection; 23 with single-use autoinjector; and 45 with reusable autoinjector. 68.4% found using the single-use autoinjector very easy or easy, versus 77.9% for the reusable device (difference ?9.5%; p = 0.200). 40.0% versus 29.5% found the respective devices very easy (difference 10.5%; p = 0.203).

Conclusions: Most patients found both autoinjectors easy or very easy to use. Having two viable options may help accommodate patient preferences. Ease of administration and patient satisfaction relates to adherence; satisfied patients may more likely be adherent.

Trial registration: The trial is registered at ClinicalTrials.gov (CT.gov identifier: NCT02019550).     

Treatment of recurrent ovarian cancer: a retrospective analysis of women treated with single-agent carboplatin originally treated with carboplatin and paclitaxel. The Memorial Sloan-Kettering Cancer Center experience

OBJECTIVE: There is no standard treatment for recurrent epithelial ovarian cancer (EOC). As there are no curative options, many oncologists choose to treat women who recur with carboplatin, particularly if they are deemed to have platinum-sensitive disease. However, particularly in the era of platinum-taxane treatment as primary therapy, the utility of this treatment has not been established, nor is it clear whether the results of single-agent treatment are equivalent to that of combination therapy. We sought to determine the outcomes for patients with platinum-sensitive EOC who were treated with carboplatin-taxane therapy and received single-agent carboplatin (C) as second chemotherapy. In addition, we sought to compare these results to the outcomes in women who received carboplatin and paclitaxel (C + T) at first relapse. PATIENTS AND METHODS: We identified 24 patients using our electronic institutional database with a histologically confirmed diagnosis of ovarian cancer that had a complete response to platinum-paclitaxel chemotherapy, relapsed greater than 6 months after treatment, and received single-agent carboplatin as second-line chemotherapy. We performed a subsequent comparison between a subgroup of this cohort and one that met the same inclusion criteria but received C + T at relapse between January 1998 and December 2000. RESULTS: Eighteen patients were evaluable for response, and all were available for analysis of survival end points. For evaluable patients, the overall response rate was 39% (complete, 11%; partial, 28%). Twenty-two percent had stable disease. Six (25%) patients experienced a hypersensitivity reaction, including 1 who required hospitalization. The median overall survival was 22 months. The 2-year overall survival rate was 49%. Stratification by treatment-free interval (TFI) showed a 25% for a TFI between 6 and 12 months and 43% for a TFI > 12 months. When a subgroup of these women (18/24) was compared to a cohort that received C + T (29), the combination was associated with a higher complete and overall response rate, 7 and 36% for C versus 45 and 71% for C + T (P = 0.02). The overall survival in women who received C was 26 months versus 42 months in the women who received C + T (P < 0.02). CONCLUSION: Carboplatin as a single agent is effective therapy for recurrent ovarian cancer in women who recur following treatment with carboplatin and paclitaxel, and the treatment-free interval predicts response to single-agent carboplatin. However, our secondary analysis suggests that carboplatin and paclitaxel may produce a higher response rate and a survival benefit compared to C alone. This supports the conclusions of ICON4, which recently reported both overall and progression-free survival benefits with C + T over C in women with platinum-sensitive recurrent disease.     

Combined modality therapy in esophageal cancer: the Memorial experience

Over the past 20 years in the United States, esophageal cancer has shown the most rapid rate of increase of any solid tumor malignancy. Esophageal cancer is an aggressive disease, and poor survival is achieved with surgery or chemoradiation therapy alone. Ongoing trials are investigating the use of preoperative chemoradiation followed by surgical resection. Chemoradiation employing a combination of cisplatin and a continuous infusion of 5-fluorouracil (5-FU) is the most commonly used therapy. The significant gastrointestinal toxicity of traditional cisplatin/5-FU-based regimens has prompted the evaluation of new agents in combined-modality therapy. The Memorial Sloan-Kettering Cancer Center has conducted chemoradiation trials with weekly paclitaxel/cisplatin and irinotecan/cisplatin, and the results suggest that this regimen has the potential to improve the therapeutic index without compromising efficacy. Randomized trials are now being conducted to evaluate the tolerance and efficacy of paclitaxel/cisplatin in comparison with paclitaxel/5-FU combined with radiotherapy in locally advanced esophageal cancer. The incorporation of these non-5-FU-based therapies with novel biologic agents is planned.     

Ca2+ transients in astrocyte fine processes occur via Ca2+ influx in the adult mouse hippocampus

Astrocytes display complex morphologies with an array of fine extensions extending from the soma and the primary thick processes. Until the use of genetically encoded calcium indicators (GECIs) selectively expressed in astrocytes, Ca²⁺ signaling was only examined in soma and thick primary processes of astrocytes where Ca²⁺‐sensitive fluorescent dyes could be imaged. GECI imaging in astrocytes revealed a previously unsuspected pattern of spontaneous Ca²⁺ transients in fine processes that has not been observed without chronic expression of GECIs, raising potential concerns about the effects of GECI expression. Here, we perform two‐photon imaging of Ca²⁺ transients in adult CA1 hippocampal astrocytes using a new single‐cell patch‐loading strategy to image Ca²⁺‐sensitive fluorescent dyes in the cytoplasm of fine processes. We observed that astrocyte fine processes exhibited a high frequency of spontaneous Ca²⁺ transients whereas astrocyte soma rarely showed spontaneous Ca²⁺ oscillations similar to previous reports using GECIs. We exploited this new approach to show these signals were independent of neuronal spiking, metabotropic glutamate receptor (mGluR) activity, TRPA1 channels, and L‐ or T‐type voltage‐gated calcium channels. Removal of extracellular Ca²⁺ almost completely and reversibly abolished the spontaneous signals while IP₃R2 KO mice also exhibited spontaneous and compartmentalized signals, suggesting they rely on influx of extracellular Ca²⁺. The Ca²⁺ influx dependency of the spontaneous signals in patch‐loaded astrocytes was also observed in astrocytes expressing GCaMP3, further highlighting the presence of Ca²⁺ influx pathways in astrocytes. The mechanisms underlying these localized Ca²⁺ signals are critical for understanding how astrocytes regulate important functions in the adult brain. GLIA 2016;64:2093–2103