Potential Benefits of Ketamine Seen in Antidepressent Clinical Trial

Clin. Invest. (2013) 3(7), 609–612

News Highlights from the latest news and research in Clinical Investigation

Potential benefits of ketamine seen in antidepressent clinical trial

The largest clinical trial to date utiliz- TX, USA) and James Murrough (Mount placebo-administered group. For both ing the anesthetic ketamine was led by Sinai, NY, USA) along with their research groups the drugs were well tolerated. researchers from the Icahn School of team. Seventy two patients with treat- Murrough summarized the study Medicine (Mount Sinai, NY, USA). ment-resistant depression (classified as findings, “We found that ketamine was The clinical trial enrolled patients diag- failure to respond to two or more med- safe and well tolerated and that patients nosed with treatment-resistant major ications) were evaluated and underwent who demonstrated a rapid antidepressant depression who were treated with ket- either a single intravenous infusion of effect after starting ketamine were able amine – and within 24 h the antide- ketamine over the course of 40 minutes to maintain the response throughout the pressant benefits of the anesthetic were or were treated with the active placebo course of the study.” He also added that reported. Traditional antidepressants midazolam. Midazolam is also an anes- for future studies, “Larger placebo-con- can normally take between several days thetic but does not possess antidepressant trolled studies will be required to more to weeks to demonstrate an improvement properties. Patients were interviewed after fully determine the safety and efficacy in depression. 24 h, and then again after 7 days had profile of ketamine in depression.” passed. The response rate was 63.8% after – Written by Priti Nagda “…within 24 h the antidepressant 24 h for patients in the ketamine-treated benefits of the anesthetic were group in comparison with 28% in the Sources: Mount Sinai Hospital, Newsroom, reported.” active-placebo group. Seven days later the news releases: www.mountsinai.org/about-us/ response to ketamine was lasting, with a newsroom/press-releases/ The mechanism of action of tradi- 47.5% response for the ketamine-treated ketamine-shows-significant-benefit-in- tional antidepressants such as selective group in comparison with 18.2% for the people-with-treatment-resistant-depression serotonin reuptake inhibitors is to control the neurotransmitter activity of norepinephrine and serotonin to cause a reduction in depression. However, with these medications the response can be largely delayed, and according to statistics from the US Department of Health, up to 60% of patients do not respond to this type of treatment. Ketamine on the other hand controls the activity of the glutamine neurotransmitter, and appears to do so much quicker than the traditional antidepressants.

“…according to statistics from the US Department of Heath, up to 60% of patients do not respond to [traditional antidepressants].”

The study was led by Dan Iosifescu (Mount Sinai, NY, USA), Sanjay Mathew (Baylor College of Medicine,

Data reported for gefitinib use in Caucasian EGF receptor mutation-positive non-small-cell lung cancer patients

Novel data from the IFUM trial, pre- on investigators assessment in patients overall survival were reported to be 91%, sented at the European Multidisciplin- treated with gefitinib using Response 9.7 months and 19 months, respectively. ary Conference in Thoracic Oncology Evaluation Criteria in Solid Tumours ver- Douillard also explained, “The safety and (EMCTO; Lugano, Switzerland), have sion 1.1. Overall response rate was 70% tolerance profile in Caucasian patients demonstrated that IRESSA™ (gefitinib; (95% CI: 61–78%).” did not show any new signal. Remark- AstraZeneca, UK) is effective for Cauca- Data from the previous IPASS study ably, the incidence of grade 3/4 adverse sian patients with EGF receptor (EGFR) demonstrated superior PFS for gefitinib events was low with 0% grade 3 rash and mutation-positive advanced non-small- compared with intravenous carboplatin/ 3.7% diarrhea.” Overall survival data will cell lung cancer (NSCLC) in the first-line paclitaxel chemotherapy in a population require longer follow up. setting, based on objective response rate of patients with advanced NSCLC in As this evidence supports the use of and progression-free survival (PFS). Asia. Explaining the significance of the gefitinib in Caucasian patients, Douillard IFUM is a Phase IV open-label, multi- novel IFUM results, Douillard noted, hopes the results will increase physician center, single-arm study aiming to charac- “The objective response rate seen in confidence in prescribing gefitinib for terize the efficacy, safety and tolerability this EGFR mutation-positive Caucasian such patients. of gefitinib in 106 EGFR mutation-pos- population is similar to that seen in the – Written by Francesca Lake itive Caucasian NSCLC patients. Jean- EGFR mutation-positive IPASS popula- Yves Douillard, principal investigator of tion. Therefore, gefitinib appears to be Source: Press release: New data presented at the study (University of Nantes Medical consistent in its efficacy in patients with EMCTO showed that first-line therapy with School, France), explained, “The primary this disease, irrespective of whether they gefitinib (IRESSATM) in Caucasian patients end point of IFUM was to evaluate the are Asian or Caucasian.” with EGFR mutation-positive advanced NSCLC objective response rate (confirmed com- The secondary efficacy end points of resulted in an ORR of 70% (95% CI 61-78). plete response or partial response) based disease control rate, median PFS and Released 10th May 2013.

The potential of Kava to be used as an alternative therapy for anxiety sufferers

A world first study led by a research chronic clinical anxiety. Unlike some Patients in the placebo group were given team from the University of Melbourne other options it has less risk of depend- dummy tablets in the same fashion. By (Melbourne, Victoria, Australia) have ency and less potential for side effects.” the end of the study, results indicated found that Kava, a plant originating The study revealed that polymor- that there had been a significant reduc- from the South Pacific, may cause a phisms in GABA transporters may mod- tion in anxiety in the patients that had significant reduction in people who suf- ify a sufferer’s response to Kava, with been taking Kava in comparison to those fer from anxiety. Kava could become a Sarris explaining that, “If this finding is in the placebo group. potential alternative therapy for the many replicated, it may pave the way for simple The effects of Kava were apparently thousands of Australians suffering from genetic tests to determine which people greater in reducing anxiety in those generalized anxiety disorders (GADs). may be likely to have a beneficial anxiety- enrollments whose GAD had been diag- GAD is a complex condition that can reducing effect from taking Kava.” nosed as moderate-to-severe. After com- drastically affect a sufferer’s quality of The 8-week study consisted of 75 pletion of the controlled phase, 6% of life with existing therapeutics possessing patients who were clinically diagnosed participants in the placebo group were only a modest clinical effect. with GAD, being administered either shown to be in remission in comparison Jerome Sarris (University of Melbourne, Kava or placebo with their anxiety lev- to the 26% of the patients in the Kava Victoria, Australia) explained the need els assessed regularly. Those in the Kava group. for newer and more effective medica- group were administered tablets contain- Kava was seen to be well tolerated tions for those suffering from anxiety, ing a water-soluble extract of Kava; the with no significant differences in patient “Based on previous work we have rec- peeled rootstock twice daily for a com- liver-function tests across either group. In ognized that plant based medicines may bined dose of 120 mg of kavalactones addition, no adverse effects were found be a viable treatment for patients with during the primary 3-week controlled that could be solely attributed to Kava chronic anxiety. In this study we’ve been phase. In the event of nonresponse, par- and there were also no differences seen able to show that Kava offers a potential ticipants were increased to a double dose in the Kava and placebo groups regarding natural alternative for the treatment of twice daily for the second 3-week phase. addiction and withdrawal.

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Further studies will now concentrate on – Written by Priti Nagda Kava in the treatment of generalized anxiety confirming the relationship between genet- disorder: a double-blind, randomized, ics and therapeutic response. The findings Sources: University of Melbourne, Melbourne placebo-controlled study. J. Clin. will be of potential benefit to both anxiety Alumni eNews: http://alumni.news.unimelb. Psychopharmacol. doi: 10.1097/ sufferers and the region of the South Pacific edu.au/clinical-trial-supports-use-kava-treat- JCP.0b013e318291be67 (2013) (Epub ahead of that relies on Kava as an export. anxiety; Sarris J, Stough C, Bousman CA et al. print).

Uncertainty over the benefits of diabetes drug in breast cancer patients

Metformin, a popular drug for diabetes as slowing tumor growth in breast cancer There are limitations to this study, as treatment, might not affect survival in breast patients. data on the stage of breast cancer and cancer patients, according to new results. The study involved 2361 diabetic women BMI were not included, and there were A new population-based study, pub- over the age of 66, all diagnosed with breast relatively short follow-up times (median lished in Diabetes Care has not shown a dif- cancer. The authors analyzed the associa- follow-up time was 4.5 ± 3.0 years). How- ference in survival from metformin use as tions between duration of metformin use ever, in general these results suggest that might have been expected, a result contrary and mortality in the population, broken more research is needed to clarify the role to some evidence that suggests the drug down into all-cause mortality and breast of metformin in cancer. improves survival in breast cancer patients. cancer-specific mortality. Of the 1101 According to Lega, “Understanding Iliana Lega (Women’s College Research deaths during the study period, 16.3% the effects of metformin on breast cancer Institute; Toronto, Canada), first author of were breast cancer specific but there was no patients is critical in helping address the the study, explains that, “Metformin is a statistically significant association between gap in cancer outcomes in patients with drug commonly used by diabetic patients cumulative metformin use and either all- and without diabetes.” Lega hopes that, to control the amount of glucose in their cause or breast cancer-specific mortality in “The findings will help physicians inform blood.” She goes on to explain the impor- the study population. treatment plans for patients with diabetes.” tance of these findings, “Although existing This population-based study differs from scientific literature suggests that drug may others in that it assessed the cumulative dose – Written by Alisa Crisp prevent new cancers and death from breast of metformin over time. Lega explained this cancer, our study found the drug did not further, stating, “What makes our study so Sources: Lega IC, Austin PC, Gruneir A, Goodwin significantly impact survival rates in our unique is that while the effects of metfor- PJ, Rochon PA, Lipscombe LL. Association patients.” min have been well documented, previous between metformin therapy and mortality after Metformin, used to lower blood sugar research has not examined the cumulative breast cancer: a population-based study. levels in Type 2 diabetes patients, works effects of the drug on patients, particularly Diabetes Care. doi: 10.2337/dc12-2535 (2013) by altering glucose production by the liver. breast cancer patients with diabetes.” Lega (Epub ahead of print); Women’s College According to other studies, metformin has continued to say that, “This is important Hospital press release: previously been suggested to confer a reduc- given that diabetic patients may switch www.womenscollegehospital.ca/assets/pdf/ tion in cancer risk of up to 30%, as well drugs over the course of their treatment.” Lega_metformin_May%202013.pdf

CUSTOM demonstrates feasibility and challenges of genetics-guided clinical trials

Researchers from the USA have recently CUSTOM is the first completed pro- Georgetown Lombardi Comprehensive presented promising findings from their spective clinical trial that employed next- Cancer Center (DC, USA). Giaccone lead CUSTOM clinical trial, which, among generation sequencing to assign cancer the CUSTOM trial while at the National other results, demonstrated that both patients to the most appropriate treatment Cancer Institute, which collaborated with patients and physicians are enthusiastic option. Patients with non-small-cell lung Oregon Health & Science University (OR, about genetics-guided cancer clinical tri- cancer, small-cell lung cancer or thymic USA) for the trial. als; researchers reached their target num- cancer were recruited, and the trial’s recep- “This was a surprise to all of us, espe- ber of participants 3 years earlier than tion exceeded the researcher’s expectations, cially since patients with advanced can- anticipated. The findings were presented “We expected it would take five years to cer who already had biopsies needed to at the 2013 annual meeting of the Ameri- enroll 600 patients into CUSTOM. But undergo an additional biopsy for the can Society of Clinical Oncology, and the in less than two years, 668 patients were study. But we found patients and their researchers propose that CUSTOM could recruited,” explained the study’s lead doctors are quite interested in this type be a model for more efficient clinical trials. investigator, Giuseppe Giaccone of the of personalized medicine. They know

future science group Clin. Invest. (2013) 3(7) 611 News that the molecular profile of the tumor the unanticipated popularity of CUSTOM patients. That is only possible with a global is important,” Giaccone added. which has reaffirmed patient and physician study that involves, potentially, hundreds In the CUTSOM trial, tumor biopsies interest in such trials, one of the end points of institutions.” from eligible patients were screened for was not met; they were unable to produce “The CUSTOM trial demonstrates both mutations in approximately 200 genes an accurate statistical analysis of response the feasibility of the approach for common using next-generation sequencing. The to novel drugs. mutations – that it is possible to have a turnaround time was 2 weeks and the trial Results for the small-cell lung cancer real-time genetic analysis that guides treat- also demonstrated that it is safe to obtain and thymic cancer groups were inconclu- ment – as well as the difficulty of studying new biopsies for genetic analysis from sive owing to not enough patients having treatment for rare mutations,” Giaccone patients with advanced cancer. the specific mutations to assess therapy concluded. CUSTOM demonstrated that patients response, as Giaccone explained, “When – Written by Sarah Miller with KRAS mutations did not benefit we started the study, we didn’t know how from selumetinib; a single agent investi- frequently the mutations occurred. Now Sources: Georgetown Lombardi Comprehensive gational drug being investigated in non we know that many mutations represent Cancer Center News Release: http://explore. -small-cell lung cancer, in addition to only 1 to 2 percent of patients and to do georgetown.edu/documents/70469/?PageTemp other cancers. However, despite this and this right, you need to screen thousands of lateID=141

The editorial team welcomes suggestions for timely, relevant items for inclusion in the news. If you have newsworthy information, please contact: Priti Nagda, Commissioning Editor, Clinical Investigation Future Science Group Unitec House 2 Albert Place London, N3 1QB, UK t: +44 (0)20 8371 6090 e: [email protected]

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