Prevention and Management of Chemotherapy-Induced Peripheral Neuropathy in Survivors of Adult Cancers: ASCO Clinical Practice Guideline

ASCO has recently published guidelines for the prevention and management of CIPN. Unfortunately, but not surprisingly even after a robust medical literature search, there are no revolutionary breakthroughs for the treatment or prevention of chemotherapy-induced neuropathy (CIPN). Here is a summary of the publication:

[You will also find this web page linked on the left hand side permanently under "Useful Links"]

"Recommendations: On the basis of the paucity of high-quality, consistent evidence, there are no agents recommended for the prevention of CIPN. With regard to the treatment of existing CIPN, the best available data support a moderate recommendation for treatment with duloxetine. Although the CIPN trials are inconclusive regarding tricyclic antidepressants (such as nortriptyline), gabapentin, and a compounded topical gel containing baclofen, amitriptyline HCL, and ketamine, these agents may be offered on the basis of data supporting their utility in other neuropathic pain conditions given the limited other CIPN treatment options. Further research on these agents is warranted."

Link to the guidelines, summary, slide deck, etc. at ASCO website: click here

Prevention and Management of Chemotherapy-Induced Peripheral Neuropathy in Survivors of Adult Cancers: American Society of Clinical Oncology Clinical Practice Guideline | ASCO.org

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"Cancer: The Emperor of All Maladies" Preview at AACR Annual Meeting 2014

"The American Association for Cancer Research (AACR), the world's oldest and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer, is proud to be an outreach partner for "CANCER: The Emperor of All Maladies," a film documentary presented by Ken Burns. Based on the book "The Emperor of All Maladies: A Biography of Cancer" by Siddhartha Mukherjee, M.D., the film will air on PBS in spring 2015. The AACR is an outreach partner for the documentary, along with Stand Up To Cancer (SU2C), a program of the Entertainment Industry Foundation (EIF) that works to accelerate innovative cancer research and to increase awareness about progress being made in the fight against the disease."

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Valproic Acid Linked with Reduced Risk of Developing Head and Neck Cancer

Sodium valproate is a common mood stabilizer (Photo credit: Wikipedia)

I was surprised to read this press release this morning concerning valproic acid, an antiepileptic, mood stabilizing medication that has also been used traditionally in the management of neuropathic pain.

I am interesting in seeing the doses most commonly encountered and the relevant toxicities. As PCF-4 (PalliativeDrugs.org) notes, no single mode of action accounts for its anti-seizure activity. It is a:

• sodium and T-type calcium channel blocker
• an NMDA receptor-channel blocker (?helpful in hyperalgesia)
• alters GABA (distinctively selective for midbrain), dopamine and serotonin transmission

T-type calcium channels have been implicated in thalamic burst firing (absence seizures), neuropathic pain and possibly in regulating pain excitation thresholds in a 'T-rich' subset of peripheral nociceptors. 

Beneficial effects have been reports in cancer-related neuropathic pain in Europe and Australia, but mixed results in other pain scenarios. Onset of action can often be within 24 hours for neuropathic pain.

But I digress - on to the news of the day:

Excerpt of Press Release via Wiley:

"A new study indicates that a commonly used mood stabilizing drug may help prevent head and neck cancer. The study is published early online in CANCER, a peer-reviewed journal of the American Cancer Society.

Valproic acid (VPA) is currently prescribed as an anti-seizure medication and mood stabilizer, but it is also being studied as an anticancer agent because it inhibits histone acetyl transferases, which help control gene expression by changing DNA structure.

Johann Christoph Brandes MD, PhD, of the Atlanta Veterans Affairs Medical Center and Emory University in Atlanta, led a team that assessed the anticancer effects of VPA in a study of 439,628 veterans, of whom 26,911 were taking the medication for bipolar disorder, post-traumatic stress disorder, migraines, and seizures.

Veterans who took VPA for at least one year had a 34 percent lower risk of developing head and neck cancer compared with those who did not take the medication. Higher doses and longer duration of VPA use seemed to provide additional benefits. No significant differences were observed for lung, bladder, colon, and prostate cancer incidences.

“A 34 percent risk reduction for the development of head and neck cancer with VPA use could result in the prevention of up to approximately 16,000 new cases and 3,000 to 4,000 annual deaths in the US alone,” said Dr. Brandes. “Head and neck cancer is an important global health crisis, and low cost and low toxicity prevention strategies like VPA use have a high potential impact on pain, suffering, costs, and mortality associated with this disease.”

Article: “Long-term use of valproic acid in United States Veterans associates with reduced risk of smoking related head-and neck cancer.” Hyunseok Kang, Theresa Gillespie, Michael Goodman, Seth Brodie, Mina Brandes, Maria Ribeiro, Suresh Ramalingam, Dong Shin, Fadlo Khuri, and Johann Christoph Brandes. CANCER; Published Online: March 24, 2014 (DOI: 10.1002/cncr.28479).

URL Upon Publication: http://doi.wiley.com/10.1002/cncr.28479

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VTE Treatment and Secondary Prevention in Cancer Patients

CancerThrombosis.org :: Treatment and Secondary Prevention: 

"The American Society of Clinical Oncology guideline: Recommendations for venous thromboembolism prophylaxis and treatment in patients with cancer
Key recommendations for secondary prevention of recurrent VTE19"

• LMWH is the preferred approach for the initial 5 to 10 days of anticoagulant treatment of the cancer patient with established VTE

• LMWH given for 6 months is also the preferred approach for long-term anticoagulant therapy. Vitamin K antagonists with a targeted INR of 2 to 3 are acceptable for long-term therapy when LMWH is not available

• After 6 months, indefinite anticoagulant therapy should be considered for selected patients with active cancer, such as those with metastatic disease and those receiving chemotherapy

• The insertion of a vena cava filter is only indicated for patients with contraindications to anticoagulant therapy and in those with recurrent VTE despite adequate long-term therapy with LMWH

• For patients with CNS malignancies, anticoagulation is recommended for established VTE as described for other patients with cancer. Careful monitoring is necessary to limit the risk of hemorrhagic complications. Anticoagulation should be avoided in the presence of active intracranial bleeding, recent surgery, preexisting bleeding diathesis such as thrombocytopenia (platelet count <50 coagulopathy="" font="" l="" or="">

• For elderly patients, anticoagulation is recommended for established VTE as described for other patients with cancer. Careful monitoring and dose adjustment is necessary to avoid excessive anticoagulation and further increase in the risk of bleeding

For full article including great summary charts and diagrams as well as other key player guidelines, click here.

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Personalized Cancer Treament, From Just a Blood Sample

Personalized Cancer Treament, From Just a Blood Sample - The Crux | DiscoverMagazine.com:



"A technique being developed by San Diego–based Epic Sciences can determine whether a cancer patient is an appropriate candidate for a drug, and even whether the drug is losing its efficacy.

In research presented last month at the Personalized Medicine World Conference in Palo Alto, CA, Epic described how their technology can be used to reliably pick out rare cells from a blood sample. In the case of cancer, these rare, circulating tumor cells could one day tell an oncologist not only whether a patient’s cancer has returned, but also whether it’s growing resistant to the current treatment regimen—something only expensive scans and invasive biopsies can do with any accuracy today."



Read the full article here

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Tumor Paint: Changing the way surgeons view and fight cancer (CNN)

Tumor Paint: Changing the way surgeons fight cancer - CNN.com:

"Olson and his team were able to identify a small protein, or peptide, in the scorpion's venom and use it to produce Tumor Paint. They grew a brain tumor on a mouse's back and injected the "paint" into a tail vein; within an hour, the cancer was lighting up. Tumor Paint was 500 times more sensitive than an MRI, and it didn't just work for brain cancer but breast, skin, prostate and colon cancers."

Link to full article here.

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Dexamethasone a Potential Treatment for Cancer-Related Fatigue (JOCO)

Dexamethasone (Photo credit: Wikipedia)

Oncology Times: "Dexamethasone helps to reduce cancer-related fatigue in patients with advanced disease, according to a double-blind, randomized, placebo-controlled trial published in the Journal of Clinical Oncology(2013;31:3076-3082)."

Highlight:

"Prior research demonstrating the benefit of steroids in advanced cancer patients is limited, and there are no validated studies using fatigue as a primary outcome,” he said. The study he led (senior author was Eduardo Bruera, MD) used validated tools in a controlled setting that met National Cancer Institute and National Comprehensive Cancer Network criteria. Moreover, the study demonstrated that dexamethasone at 4 mg twice daily was effective in treating cancer-related fatigue for a period of two weeks."

Link to full article here.

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Tricyclic Antidepressant Imipramine May Combat Small Cell Lung Cancer (Stanford University School of Medicine)

English: Cancer cells photographed by camera attached to microscope in time-lapse manner. (Photo credit: Wikipedia)

FDA-approved antidepressant may combat deadly form of lung cancer, study finds - Office of Communications & Public Affairs - Stanford University School of Medicine: 

Excerpts:

"...The phase-2 trial is now recruiting participants with small-cell lung cancer and other, similar conditions like aggressive gastrointestinal neuroendocrine cancers. The “repositioning” of an existing drug to treat a disorder other than the one for which it was originally approved is an example of how extremely large genetic and biological databases are changing the face of medicine."

"...Specifically, the drugs activated a cellular self-destruct pathway that killed the cancer cells."

"...The pipeline works by scanning the hundreds of thousands of gene-expression profiles (gathered by multiple researchers and stored in large databases) across many different cell types and tissues — some normal and some diseased, some treated with medications and some not. Alone, these profiles may not mean much to any one investigator or group, but when viewed together, researchers can pick out previously unsuspected patterns and trends."

"Jahchan tested the effect of a tricyclic antidepressant called imipramine on human small-cell lung cancer cells grown in the laboratory and growing as tumors in laboratory mice. She found that the drug was able to potently activate a self-destruction pathway in the cancer cells and to slow or block metastases in the animals. The drug maintained its effectiveness regardless of whether the cancer cells had previously been exposed, and become resistant, to traditional chemotherapy treatments. Another drug, an antihistamine called promethazine, identified by the bioinformatics screen, also exhibited cancer-cell-killing abilities."

"Further investigation showed that the drugs appear to work through a class of molecule on the cancer cells’ surfaces called G-protein-coupled receptors, but the researchers are continuing to investigate exactly how the drugs specifically kill neuroendocrine cancer cells."

See more at: http://med.stanford.edu/ism/2013/september/antidepressant.html#sthash.OzJhnFka.dpuf

Link to full article here. 

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Lab Notes: Chemo Patients Going to the Dogs

English: Author: Andrew Ryzhkov Rotation of the model of the Paclitaxel molecule generated by the ViewMol3D program. http://redandr.ca/vm3/viewmol3d_gallery.htm (Photo credit: Wikipedia)

Lab Notes: Chemo Patients Going to the Dogs: "From Dog Food to Chemo?

From Dog Food to Chemo?

"A chemical commonly used as a preservative in dog food prevented the development of peripheral neuropathy associated with treatment with paclitaxel (Taxol) in a mouse model.

The majority of patients given paclitaxel for malignancies such as breast cancer experience painful neuropathy, which can be dose-limiting and can seriously impair quality of life. So a group of researchers from Johns Hopkins led by Ahmet Hoke, MD, PhD, screened some 2,000 compounds for neuroprotective effects in various cell lines.

They identified the antioxidant ethoxyquin -- approved by the FDA for use in animal feed 50 years ago -- as having the most pronounced effects. When they co-administered ethoxyquin with paclitaxel in mice, the intraepidermal nerve fiber damage that predictably occurs in the animals' paws didn't develop.

Hoke's team then were able to identify heat shock protein 90 as the molecule that mediated the neuroprotection through its effects on the levels of two proteins known as ATXN2 and SF3B2.

These findings suggest that ethoxyquin and its derivatives might be suitable for development to help prevent chemotherapy-induced nerve damage in the clinical setting, the researchers suggested in the Annals of Neurology."

- Via Medpagetoday

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A healthcare innovator’s guide to must-know tech terms for the next decade of medicine | MedCity News

Personalized Medicine (Photo credit: Wikipedia)

A healthcare innovator’s guide to must-know tech terms for the next decade of medicine | MedCity News:

Excerpt:

Precision medicine

"From targeted cancer drugs to molecular diagnostics, advances in genome sequencing are driving precision medicine. It’s defined by Pfizer as “an approach to discovering and developing medicines and vaccines that deliver superior outcomes for patients, by integrating clinical and molecular information to understand the basis of disease.”

Some use precision medicine synonymously with personalized medicine. Others say it’s a better term that captures the idea of personalized medicine more clearly: Not as medical care that’s tailored to an individual but rather the ability to classify individuals into smaller populations that might be more susceptible to certain diseases or respond to drugs differently. This term has been slowly gaining steam since 2011."

Read more: http://medcitynews.com/2013/08/a-healthcare-innovators-guide-to-must-know-tech-terms-for-the-next-decade-of-medicine/#ixzz2dSvxYbjO

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Long-Term Treatment With Imatinib Affected Bone Mineral Density - Cancer Network

Crystal structure of the c-abl kinase domain (green) in complex with Sti-571 (imatinib, red). Rendered with Accelrys DS Visualizer Pro 1.6 and edited in the GIMP. Conformation and style made to match Image:Bcr abl sti.jpg, originally created by Mxpule for use in Wikipedia. (Photo credit: Wikipedia)

Long-Term Treatment With Imatinib Affected Bone Mineral Density - Cancer Network by Leah Lawrence: 

Highlights:

"A majority of patients on imatinib(Drug information on imatinib) for treatment of gastrointestinal stromal tumor (GIST) or chronic myelogenous leukemia (CML) had low or absent levels of osteocalcin, a bone marker secreted by osteoblasts, and about 50% of patients had a decrease in bone mineral density, signaling that long-term treatment may affect bone health in these patients.

The results were published in Leukemia Research.

Berman and colleagues enrolled 28 patients with either CML or GIST, and prospectively analyzed levels of osteocalcin and serum N-telopeptide of type 1 collagen(Drug information on collagen) (NTX), a marker of bone resorption. Patients were on imatinib for a median of 31 months at baseline. Nineteen patients completed measures of bone mineral density at baseline, 1 year, and 2 years.

Ninety-five percent of the patients were found to have low levels of osteocalcin, and 37% of patients had no measurable amounts at least once during the study period.

Eleven patients (58%) had normal NTX levels. Only four patients (21%) had elevated levels of NTX, and four patients had low levels of NTX.

At 2 years, DEXA scans indicated that 47% of patients had a decrease in bone mineral density and 32% had no change. Seven of the nine patients with decreases saw significant changes at the total hip.

“Imatinib appears to halt or at least decrease bone growth,” Berman said. “Bone is always growing or remodeling. It slows when you are older, in postmenopausal women particularly, but it is always a living organ.”

***
Of course, current practice is to give imatinib indefinitely. The authors, then, suggest careful monitoring of bone density and should the patient have indication of loss, consider therapy with calcium and vitamin D. They stated hormone therapy may need to be started. The role of bisphosphonates will also have to be later established.

Full article - click here

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"Miracle Foods" – Can They Decrease the Risk of Cancer?

Nutrition (Photo credit: Susan von Struensee)

(From: Routledge, A Member of the Taylor & Francis Group www.tandfonline.com)

Cancer is a disease that invokes fear, so it is not surprising that the public is eager to identify ways to decrease the risk. The media often features information on “Miracle Foods” and publicizes whether these foods can actually decrease the risk of cancer. 

Reality Check: There is No Such Thing as a Miracle Food, published in Volume 65, Issue 2 2013 of Nutrition and Cancer: An International Journal, is a commentary written by the University of Minnesota's Maki Inoue-Choi, Sarah Oppeneer, and Kim Robien that calls on both researchers as well as media sources to consider the validity of multiple studies as opposed to singular studies before assuming that media information is factual.

"Nutritional scientists and epidemiologists should be cognizant of the public health messages that are taken away from their individual studies and not sensationalize the findings or contribute to the media frenzy around a single study," the authors believe. 

The authors mention two separate studies that theorize a decreased risk of ovarian cancer due to flavonoids in red onions and omega-3 in sea bass. Both of these studies were reported as fact on a popular television talk show.  The authors assert that with further research, three other studies would have been found that can disprove the findings reported as true.  

"The public needs more information about the effect of diet as a whole on cancer risk, as well as the importance of achieving and maintaining an ideal body weight, regular physical activity, and avoiding a sedentary lifestyle," the authors wrote.     

*FREE ACCESS - Reality Check: There is No Such Thing as a Miracle Food

Abstract:

"A recent episode of the Dr. Oz Show suggested endive, red onion, and sea bass as foods that can decrease the risk of ovarian cancer by up to 75%. However, the scientific evidence supporting these recommendations is limited. This commentary discusses some of the concerns related to the promotion of “miracle foods” by the media. Nutritional scientists and epidemiologists should be cognizant of the public health messages that are taken from their individual studies and not sensationalize the findings of a single study."

About Nutrition and Cancer: An International Journal
Nutrition and Cancer: An International Journal reports on current research and findings relative to the effects of nutrition on the etiology, therapy, and the prevention of cancer. The Journal presents original papers by experts around the world.

EDITOR: Leonard A. Cohen
2.783 Impact Factor (© 2012 Thomson Reuters, 2011 Journal Citation Reports®)
Print ISSN: 0163-5581 • Online ISSN: 1532-7914
Volume 65, 2013, 8 issues per year 
www.tandfonline.com/HNUC

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Cancer Rates in Canada: National Post Infographic

Cancer rates in Canada: Graphic | Graphics | News | National Post:

"Cancer killed 74,529 Canadians in 2009, making it the country’s top cause of death. With this in mind, the National Post’s Richard Johnson breaks down which cancers are killing us."

Click here to see NP's infographic regarding cancer numbers in Canada.

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Ty Ulmer: Making the Biggest Save of His Life

The Hockey Writers' Shawn Reznik with an inspirational story of Ty Ulmer, who picked up hockey after battling osteosarcoma.

Excerpt:

Wise Beyond His Years

“I look at life much differently than I used to,” stated Ulmer.  ”Going through something like cancer treatment will do that to a person.  I live my day-to-day life like everyone else should…day by day.  Take every day with a grain of salt and what happens, happens.”

So you’re probably wondering how Ty is doing up to this point in his life.  Well…so far so good!

“Everything has been going smoothly.  My recent set of post-treatment scans were all clear.  No sign of recurrence in the disease.  I am now, currently, 4 years cancer free,” the upbeat 17-year old said.

The reason he is still cancer free is because he never stopped pressing on against the uphill battle.

“I didn’t give up because I wasn’t just fighting for myself.  I was fighting for my family and friends.  I was fighting for all the kids who had also battled cancer alongside me, and for those who lost their battle, as well.  I’ll never give up on anything that will not give up on me.”

We all look up to superstars, celebrities, musicians, athletes, the whole gamut.  Ty’s role models and support group are the ones who have been by his side through the cancer, the amputation, the chemo, the good news, the bad news, and just about everything else he’s experienced.

“My Dad for having been in the Air Force for 21 years, numerous deployments, missing countless things like birthdays, holidays and milestones in our family, and yet still keeping a positive attitude and making me feel loved.  I am amazed by his courage and I am honored to call him my father.

My Mom for understanding the choices I’ve made, supporting me in those choices, putting up with me, and always being there for me after it all.  For staying strong when my Dad was deployed, and keeping me in good spirits.  I am amazed by her strength and I am very thankful that she is my mother.

My Brother for being the role model he has been throughout my life, always being someone to look up to, for moving back home when he heard I was diagnosed, and helping me with going through all that I have. Always being able to cheer me up if I was feeling depressed.

I couldn’t be happier with the family I have, as they are my true role models.”

There are many people in similar situations as Ty Ulmer, who never get the opportunity he’s been given.  He’s able to play the game that has brought him so much joy.  He’s been given a second chance – of which he never takes for granted.  He’s been supported by friends and family members unconditionally.  He’s experienced things in 17 years of life that people wish they never experience at all.  And still, he remains a humble kid from Meridian, Idaho.

“I decided to play [hockey] because I have a passion for the sport that not everyone has.  I’d enjoy nothing more than to play in goal on any team – beer league or higher.  You don’t have to pay me to play, I just love the game.  I want to play because it’s something that not everyone can do, and I want to show that even the difficult things in life are worth the fight,” Ulmer stressed.

In terms of sport, his goal is quite simple: “to be able to play hockey, and teach others to play hockey (be it kids, teens, adults, or disabled).”

His message to the kid’s in the same position as he once was: “As cliché as it might sound, just don’t give up and keep your head up.  You are lucky enough to have your life, where as not everyone else is.  Life is a gift that you have been given, a gift that isn’t returnable, it is yours to keep, so live it as best as you can, and keep your spirits up.”

The kid has been through it all.  He’s visited the depths of hell and came out clean on the other side.  Cancer carved away at his body like a freshly cut pair of skates against a perfect sheet of ice.  Each slice left an indelible mark on his character, fortitude, and and will power.  Be that as it may, there is only one key point to take out of this piece.

Ty concluded, “Anything, no matter how hard it might be, is possible.  It might take a while to get there, and it might not be the easiest thing in the world, but in the end, it is worth it.”

*Read the full inspirational story at The Hockey Writers. 

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LUNGevity Foundation Hosts Third Annual Hope Summit During May, Lung Cancer Hope Month

Cancer survivors park 2 (Photo credit: Loco Steve)

(WASHINGTON, January 31, 2013) — "LUNGevity Foundation, the nation’s largest lung cancer-focused nonprofit, is inviting lung cancer survivors from across the nation to register for the 2013 LUNGevity Hope Summit taking place May 3-5, 2013 in Arlington, VA. The two day conference, taking place during Lung Cancer Hope Month, is designed for lung cancer survivors of all ages and stages of disease, currently in or out of treatment. 

The summit provides an opportunity for participants to celebrate lung cancer survivorship, and gives survivors the opportunity to learn, collaborate, advocate and use their voices and stories to make a difference in the fight against lung cancer. 

The topics to be addressed at this year’s Hope Summit will include inspirational speakers, medical expert forums, advocacy forums, lung cancer survivor-specific sessions, and opportunities for lung cancer survivors to share and connect with other survivors. There will be sessions specifically for survivors in active treatment and others for those out of treatment to address their specific needs.

Hope Summit attendees from previous years describe the value of the summit in very personal terms:

”Being in a room with 50 or so cancer survivors is an awe-inspiring event. Being in a room with 50 or so LUNG cancer survivors is as life-changing as the disease itself. Thank you all for an amazing weekend. “ - Alan

“The LUNGevity Hope Summit gave me the powerful sense of community that I often see in other groups, such as breast cancer or HIV/AIDS survivors, which I had not experienced since my lung cancer diagnosis.  Your inspirational speakers, medical experts, advocacy training, and lung cancer survivor-specific workshops will be key in empowering us as cancer survivors to connect with other survivors and share our stories” - Jose

LUNGevity designated May as Lung Cancer Hope Month to celebrate the hope for better treatments and cures for lung cancer, as well as improving lung cancer survival rates and ensuring a higher quality-of-life for lung cancer patients and their loved ones. To register for the event and to learn more, go to: www.lungevity.org/HOPESUMMIT. 

LUNGevity is offering a limited number of travel grants, based on need and availability. Deadline for grant applications is March 30. LUNGevity Foundation is also offering Community Partnerships to select organizations.  Please contact Katie Brown, LUNGevity Director of Support and Advocacy, at kbrown@lungevity.org with any questions related to the Hope Summit or Community Partnerships.

About LUNGevity Foundation

The mission of LUNGevity Foundation is to have a meaningful impact on improving lung cancer survival rates, ensure a higher quality-of-life for lung cancer patients and provide a community for those impacted by lung cancer. It does so by supporting critical research into the early detection and successful treatment of lung cancer, as well as by providing information, resources and a support community to patients and caregivers.

LUNGevity seeks to inspire the nation to commit to ending lung cancer.

About Lung Cancer

• 1 in 14 Americans is diagnosed with lung cancer in their lifetime
• Lung cancer is the leading cause of cancer death, regardless of gender or ethnicity
• Lung cancer kills almost twice as many women as breast cancer and more than three times as many men as prostate cancer
• About 55% of all new lung cancer diagnoses are among people who have never smoked or are former smokers
• Only 16% of all people diagnosed with lung cancer will survive 5 years or more, BUT if it’s caught before it spreads, the chance for 5-year survival improves dramatically"

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