Nifedipine in the management of preterm labor: a systematic review and metaanalysis


Objective

To determine the efficacy and safety of nifedipine as a tocolytic agent in women with preterm labor.

Study Design

A systematic review and metaanalysis of randomized controlled trials.

Results

Twenty-six trials (2179 women) were included. Nifedipine was associated with a significant reduction in the risk of delivery within 7 days of initiation of treatment and before 34 weeks’ gestation, respiratory distress syndrome, necrotizing enterocolitis, intraventricular hemorrhage, neonatal jaundice, and admission to the neonatal intensive care unit when compared with β2-adrenergic-receptor agonists. There was no difference between nifedipine and magnesium sulfate in tocolytic efficacy. Nifedipine was associated with significantly fewer maternal adverse events than β2-adrenergic-receptor agonists and magnesium sulfate. Maintenance nifedipine tocolysis was ineffective in prolonging gestation or improving neonatal outcomes when compared with placebo or no treatment.

Conclusion

Nifedipine is superior to β2-adrenergic-receptor agonists and magnesium sulfate for tocolysis in women with preterm labor.

source: science direct

Cancer Therapy Associated Bone Loss: Implications for Hip Fractures in Mid-Life Women with Breast Cancer


Aromatase inhibitors (AIs) have been recently associated with hip fractures. We present a case series of breast cancer survivors and a systematic review of bone health care in breast cancer.

Experimental Design: We completed clinical assessments and bone density testing (BMD) of hip fractures from January 2005 to December 2008. Prefracture and 12-month functional status was obtained. Systematic review included case reports and review of MEDLINE, PubMed, EMBASE, and Food and Drug Administration Adverse Event Reporting System (FDA AERS) from January 1998 to December 2008 (search terms: breast cancer, bone loss, osteopenia, osteoporosis, malignancy, cancer treatment, menopause, adriamycin, cytoxan, tamoxifen, and AIs).

Results: Median age was 53.5 years; five women had osteopenia, one osteoporosis. Five cases were ER (+), and received surgery, XRT chemotherapy, and anastrozole. Functional decline was noted at 12 months, with difficulty in performing heavy housekeeping, climbing stairs, and shopping. The FDA AERS database included 228 cases of fractures associated with breast cancer therapy; 77/228 (29.4%) were hip or femur fractures. Among mid-life women under the age of 64 years there were 78 fractures; 15/228 (19%) were hip and femur fractures. AIs were the most common drug class associated with fractures (n = 149, 65%).

Conclusions: Cancer treatment induced bone loss results in hip fractures among mid-life women with breast cancer. Hip fractures occur at younger ages and higher BMD than expected for patients in this age group without breast cancer. Hip fractures result in considerable functional decline. Greater awareness of this adverse drug effect is needed.

source: cancer research

Selective Serotonin Reuptake Inhibitors in Stroke Recovery


Fluoxetine may improve motor outcome after ischemic stroke.

Pharmacotherapy for motor deficits caused by brain injury has been a subject of investigation for many years. Some selective serotonin reuptake inhibitors (SSRIs) improved motor recovery after stroke in several small clinical trials but have not been extensively examined in this context. Now, researchers have conducted a multicenter study to examine the effect of fluoxetine on motor outcome in patients with moderate-to-severe motor deficits after stroke.

Between 5 and 10 days after an ischemic stroke, 113 patients were randomized to receive 20 mg of fluoxetine or placebo daily for 90 days. In addition, all participants had the standard physiotherapy provided at their sites. The groups were well matched for baseline demographic characteristics, vascular risk factors, stroke location and severity, and administration of thrombolytic agents. The dropout rate was low. The primary outcome was the change between baseline and 90 days in the Fugl-Meyer Motor Score (FMMS), a well-validated, reliable measure of neurological function that is frequently used in rehabilitation-related clinical investigation. Secondary endpoints were changes on the NIH Stroke Scale, modified Rankin Scale (mRS), and Montgomery-Asberg Depression Rating Scale (MADRS).

Compared with the placebo group, the fluoxetine group had a significantly greater improvement in the adjusted mean FMMS, and a significantly greater percentage had mRS scores in the independent range at 90 days. MADRS scores indicated that fewer fluoxetine recipients than placebo recipients had depression at 90 days; nonetheless, after adjustment for depression diagnosis during the treatment period, the FMMS remained significantly higher in the fluoxetine group. Adjustment for treatment with thrombolytic agents did not alter the FMMS findings. Adverse events were similar in both groups and did not interrupt treatment.

Comment: This well-designed study extends previous observations that SSRIs may improve motor outcomes after ischemic stroke. Treatment was well tolerated, and the observed gain in FMMS was in a range recognized as clinically significant. The shift toward greater independence measured by the mRS supports the conclusion that the fluoxetine effect was ecologically meaningful. The investigators speculate that the benefit of fluoxetine was mediated by enhancement of neuroplasticity associated with recovery. They argue against this being solely an antidepressant effect, although the underlying mechanism awaits further investigation. This study is relatively small; ideally, a more definitive trial will confirm these results. Nevertheless, SSRIs may be a valuable addition to the stroke clinician’s therapeutic toolbox and should be considered as an adjunct to physiotherapy in the rehabilitation of motor deficits in moderate-to-severe stroke.

— Gary Abrams, MD

Dr. Abrams is Director of the Neurorehabilitation Clinic, University of California, San Francisco, Medical Center.

Published in Journal Watch Neurology February 1, 2011

Second-Line Panitumumab for Colorectal Cancer


Adding panitumumab to chemotherapy improved progression-free survival and response rate, but not overall survival, in patients with KRAS wild-type CRC.

Advances in first- and second-line chemotherapy have improved the rate of overall survival (OS) in patients with metastatic colorectal cancer (CRC). The anti–epidermal growth factor receptor (EGFR) agents cetuximab and panitumumab are effective for treating patients with advanced CRC who have KRAS wild-type tumors, and treatment with cetuximab plus chemotherapy in first- and second-line therapy has been associated with benefits in progression-free survival (PFS) and antitumor response. Moreover, a recent study demonstrated the effectiveness of panitumumab as part of first-line chemotherapy in patients with KRAS wild-type CRC (JW Oncol Hematol Jan 25 2011).

Now, industry-supported investigators report results of the first study to evaluate panitumumab as part of second-line chemotherapy for nearly 1200 patients with metastatic CRC and disease progression despite one prior chemotherapy regimen. Patients were randomized to receive fluorouracil, leucovorin, and irinotecan (FOLFIRI) with or without panitumumab (6 mg/kg) every 2 weeks. Of 1083 patients with tissue available for KRAS testing, 55% had KRAS wild-type tumors and 45% had KRAS mutant tumors.

Among KRAS wild-type patients, panitumumab recipients fared significantly better than nonrecipients in terms of PFS (median, 5.9 vs. 3.9 months; hazard ratio, 0.73; P=0.004) and response rate (35% vs. 10%; P<0.001), but not OS (14.5 and 12.5 months). Among patients with KRAS mutant tumors, panitumumab recipients and nonrecipients achieved similar PFS (5.0 and 4.9 months), RR (13% and 14%), or OS (11.8 and 11.1 months).

Comment: Second-line therapy with FOLFIRI plus panitumumab was more effective than FOLFIRI alone in patients with metastatic KRAS wild-type CRC. These findings are consistent with data from similar trials showing that second-line therapy with cetuximab improved PFS and RR, but not OS. Given the lack of an OS benefit in the current study, it is appropriate to attempt second-line chemotherapy alone, without panitumumab, in patients with KRAS wild-type CRC and to consider adding panitumumab if the disease progresses.

David H. Ilson, MD, PhD

Published in Journal Watch Oncology and Hematology February 1, 2011