A recent review of studies with intra-arterial administration of nitrosoureas and platinum derivatives, as well as the principal aspects and perspectives of the new strategy of blood–brain barrier disruption with osmotic agents or bradykinin analogs demonstrated no superiority of intra-arterial chemotherapy over its intravenous counterpart . It concluded that although the incidence of serious neurotoxicity is reduced with teh intra-arterial route, the risk of  acute complication still contraindicates internal carotid or vertebral artery catheterization for chemotherapy administration outside the setting of well-controlled clinical trials.

IUmberto Basso, Sara Lonardi, Alba A Brandes, Is intra-arterial chemotherapy useful in high-grade gliomas? Expert Review of Anticancer Therapy
October 2002, Vol. 2, No. 5, Pages 507-519

Herbert B. Newton. (2005) Intra-arterial chemotherapy of primary brain tumors. Current Treatment Options in Oncology 6:6, 519-530

CrossRef Maciej M Mrugala, Santosh Kesari, Naren Ramakrishna, Patrick Y Wen. (2004) Therapy for recurrent malignant glioma in adults. Expert Review of Anticancer Therapy 4:5, 759-782

Link to the original article

nccn.org, melanoma

Wen-Jen Hwu, MD, PhD, HemOnc Today, Targeted therapy for metastatic melanoma: From bench to bedside  June 25, 2010

Link to the original article

Caris Target Now purports to help treating physicians create a cancer treatment plan based on the tumor tested. By comparing the tumor's information with data from published clinical studies by thousands of the world's leading cancer researchers, Caris claims to be able to help determine which treatments are likely to be most effective and, just as important, which treatments are likely to be ineffective.

This approach represents a cutting edge of diagnostic science, sometiems termed, "Personalized Medciine". The concept that one can individualize cancer therpay based on specific tumor characteristics is attractive but needs to be proven before being widely adapted. As of now, there is little evidence to support it and no guidelines or professional bodies recommending it.

Caris writes on its website: "Our evidence team has reviewed more than 60,000 clinical literature manuscripts that support associations between biomarkers and treatments.  The Caris Target Now database is continually updated with the latest research and emerging biomarker information.

This ongoing process ensures that only the most relevant and appropriate tests are included in the Caris Target Now panel. Better information can lead to better decisions. Better decisions can lead to better health outcomes."

This processand  information remains proprietary and not peer-reviewed.

http://www.jnccn.org/content/7/2/109.full.pdf

Companion Diagnostics in Personalized Medicine and Cancer Therapy

Trimark Publications (190 pages), published Apr 2008

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Weide R, Hess G, Köppler H, Heymanns J, Thomalla J, Aldaoud A, Losem C, Schmitz S, Haak U, Huber C, Unterhalt M, Hiddemann W, Dreyling M; German Low Grade Lymphoma Study Group.
High anti-lymphoma activity of bendamustine/mitoxantrone/rituximab in rituximab pretreated relapsed or refractory indolent lymphomas and mantle cell lymphomas. A multicenter phase II study of the German Low Grade Lymphoma Study Group (GLSG). Leuk Lymphoma. 2007 Jul;48(7):1299-306.

V. Gandhi and J. A. Burger
Bendamustine in B-Cell Malignancies: The New 46-Year-Old Kid on the Block
Clin. Cancer Res., December 15, 2009; 15(24): 7456 – 7461.

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For acute myelogenous leukemia (AML), less is known. A 2007 review, looked at 33 patients with the World Health Organization (WHO) criteria of AML that were treated with decitabine alone (23 patients) or in combination with valproic acid (10 patients) as first-line therapy. There were 20 men (61%) and their median age was 72, range 39 to 85. Median bone marrow blasts at study entry was 26%, and 14 (42%) had >30% blasts. There were three different schedules of decitabine IV, which gave a total of 100–150 mg/m2/course over 3–10 days. Of the 33 patients treated, there were 8 CRs (24%) and 9 marrow CR/PR/Hematologic improvement (27%) for a total response rate of 17 (52%). Overall mortality at 4 weeks and 8 weeks was 3% and 15%, respectively. At a median follow-up of 20 months, median survival of the entire group was 12.6 months (95% CI: 6.5–23.0), and 2-year survival was 25% (95% CI: 13–48), which compares favorably to reported AML survival in this age group in the United States. The study concluded that decitabine is an effective and less toxic treatment in this AML age group and may prolong survival compared with supportive care.

Similarly, Dacogen is being sued for maintenance in his case.

MGI Pharma is currently conducting a phase III pivotal trial to evaluate Dacogen in patients with AML. Additional phase II studies are also underway to evaluate alternative dosing regimens for Dacogen in patients with MDS, AML and chronic myelogenous leukemia. For maintenance there is: Decitabine as Maintenance Therapy After Standard Therapy in Treating Patients With Previously Untreated Acute Myeloid Leukemia, NCT00416598

Thus, it is still experimental.

REFERENCES:

Silverman L, Demakos E, Peterson B, et L. Randomized controlled trial of azacitidine in patients with the myelodysplastic syndrome: a study of the Cancer and Leukemia Group B. J. Clin. Oncol 2002; 10: 2241-2252.

Saba H, Rosenfeld C, Issa JP, et al. First Report of the Phase III North American Trial of Decitabine in Advanced Myelodysplastic Syndrome. American Society of Hematology Meeting. San Diego, Calif. 2004. Abstract #64.

Kantarjian H, O'Brien S, Giles F, et al.Decitabine Low-Dose Schedule (100 mg/m2/Course) in Myelodysplastic Syndrome (MDS). Comparison of 3 Different Dose Schedules.American Society of Hematology Meeting. Atlanta, Georgia. 2005. Abstract #2522.

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The Scottish Medicines Consortium does not recommend azacitidine (Vidaza®) for use within NHS Scotland for the treatment of adults who are not eligible for haematopoietic stem cell transplantation (SCT) with intermediate-2 and high-risk myelodysplastic syndrome (MDS), chronic myelomonocytic leukaemia (CMML) or acute myeloid leukaemia (AML).

Michael Grövdal et al, Maintenance treatment with azacytidine for patients with high-risk myelodysplastic syndromes (MDS) or acute myeloid leukaemia following MDS in complete remission after induction chemotherapy, B ritish Journal of Haematology
Volume 150 Issue 3, Pages 293 – 302, 2010

Reference: No. (589/09)
Source: Scottish Medicines Consortium (SMC)
Date published: 12/04/2010 16:30
http://www.nelm.nhs.uk/en/NeLM-Area/Evidence/Drug-Specific-Reviews/SMC-does-not-recommend-azacitidine-Vidaza-for-MDS-CMML-or-AML/

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Dear THB Reader -

What do you want first? The good news or the bad?

The good news is, cancer deaths are declining. According to the American Cancer Society’s "Cancer Statistics, 2010" report, around 767,000 cancer deaths have been avoided since the 1990s.

The bad news? Cancer is still a big problem. American Cancer Society researchers estimate that some 569,490 people will die from cancer this year.

But there is also some better news. You can take positive action to drastically reduce your own cancer risk – without doctors, surgery, or expensive drugs.

Contributing Editor Starr Daubenmire has come up with a report all about the world’s strongest anti-cancer substance. It’s all-natural. It’s up to 1,000 times stronger than anything the medical or pharmaceutical industries have ever come up with. And if you make full use of it? You could cut your risk of cancer by 50%.

THB reader Clare S. said of Starr’s article, "I just want to thank you for letting me know the importance of [this substance]. I am lacking in this [substance] and I will endeavor to take it every single day now. My mother has cancer so I am so glad I read this article."

"This is incredible and at the same time fantastic," wrote Augustus. "This resource is free … and yet a lot of people die from various kinds of cancer. Thank you very much for this very important message."

Peter W. thought Starr’s article “was very informative … just printed it for my friend who has prostrate cancer and just hope it helps him."

It’s highly unlikely that you’ll hear about this anti-cancer substance from your doctor or anyone in the medical industry… So make sure you read Starr’s full article below.

And be sure to let us know what you think of it!

To Your Best Health,

To your health,

Ian Robinson,
Managing Editor, Total Health Breakthroughs

Cut Your Risk of Any Cancer in Half – Starting Today!

By Starr Daubenmire, Contributing Editor

The mainstream medical establishment doesn’t want you to know this… because they make so much money by keeping you in the dark…

But you can cut your risk of contracting any form of cancer in half – right now – with the information in this article.

Cancer is caused by stress – biological, psychological, chemical and physical stress. In modern times the stress has increased geometrically because of pollution, artificial foods and other factors.

But eons ago Nature created an antidote to stress – a natural hormone that stimulates the body’s immune system. If you make full use of this natural defense, studies show you can cut your risk of cancer in half.

I am talking about the world’s strongest anti-cancer hormone. In terms of prevention, it is probably a thousand times stronger than any substance that the medical and drug industry has ever come up with.

One very important – but largely ignored – study found that that 30% of all cancer deaths – which amounts to 2 million world-wide and 200,000 in the U.S. – could be prevented each year with higher levels of this hormone.

In addition to that:

• One study followed 400 postmenopausal women for four years and found that the group that had sufficient levels of this hormone had a 60% lower rate of all forms of cancer.
• Another study of 900 men found that the group that lacked this hormone had a 50% higher risk of cancer of the prostate.
• A third study found that people who have a high level of this hormone are 40% less likely to develop colon cancer..

Would you like to know what this hormone is?

Then sit back because this may surprise you.

The world’s most powerful anti-cancer hormone turns out to be something quite common: Vitamin D!

Surprised?

Don’t be. This is a scientific truth that the medical establishment consistently refuses to disclose.

They have even beclouded this truth by mis-naming the hormone. They call it a vitamin but it is not a vitamin at all.

Vitamin D is a hormone that you can get in modest doses from food and supplements, but most effectively from the sun.

That’s right. The sun is Nature’s primary stimulus for the creation of Vitamin D.

I’ll bet you have never heard that before.

If you are like most people you’ve heard that the sun is a bad thing. You have been told that it is the main cause of skin cancer.

But that is absolutely false and dangerously misleading.

I will explain why that is true later in this essay. I will also explain how the sun can stimulate all the Vitamin D your body needs. Plus you’ll learn why the media has spooked you into believing that you should avoid the sun.

Moreover, I’ll tell you why you should NEVER use conventional sun blocks…not on yourself or your children.

This is a report you must read.

Why has this information been kept from you? Maybe it’s because the healing energy of the sun is free.

When a cure like this is free, nobody stands to make a profit but you. So it is understandable that Big Pharma, Big Medical and Big Government – all of whom make billions every year off cancer – don’t want you to know.

Vitamin D Has Been Vilified by the Sunscreen Industry

Before sun block became popular in the 1960s, people believed that the sun was good for you. And for good reason. Our bodies respond positively to a natural amount of exposure to the sun. It makes us feel warm. It seems to “bake” out aches and pains. It even makes us look healthy.

Too much exposure to the sun, however, has the opposite effect. It causes us pain and discomfort. It makes us wish we hadn’t stayed out in the sun so long.

Sun block was created to prevent sunburn. And because it was effective in doing so, it caught on. So strongly in fact that it soon became a billion dollar industry.

With all those millions in profits, sun block makers funded studies. And those studies show a positive correlation between repeated sunburns and two non-lethal forms of skin cancer: basal cell and squamous cancers.

But none of these studies proved that the sun was the leading culprit in basal cell and squamous cancers. And none of them detected any relationship between sunburn and melanoma, which is the one cancer that kills.

Melanoma often appears between the toes and in other areas of the body where “the sun never shines.” If the sun were the leading cause of skin cancer, how could that be?

The studies that were funded by the sun block companies never bothered to answer these questions. Instead they lobbied the government to spread the word that the best way to prevent all forms of skin cancer (including melanoma) was to use sun block. And so the myth was born!Here are a few facts that you should know about sun block and skin cancer:

Sunscreen blocks your production of vitamin D –A sunscreen with an SPF of 8 reduces your ability to produce vitamin D by more than 95 percent. A sunscreen with an SPF of 15 reduces vitamin D production by more than 99 percent.

Lifeguards in Australia have the lowest rates of melanoma – In the February 2005 issue of the Journal of the National Cancer Institute a study confirmed that exposure to the sun reduces the risk of skin cancer. Additional studies have shown that lifeguards in Australia have the lowest rates of melanoma.

Sunscreen does not block all the rays of the sun – Most sunscreens block only the UVB rays that burn your skin. They allow you to stay in the sun for hours without burning, while your skin soaks up the highly penetrating UVA radiation.

Unfortunately, most people believe that sunburn protection equals skin cancer protection. Actual evidence suggests to the contrary – that excessive exposure to non-burning UVA rays not blocked by common sunscreens induces skin cancers including the deadly melanoma variety.

Sunscreen contains several carcinogenic substances, some of which are activated by the sun! – one of the most common ingredients in commercial sunscreens is PABA, which can produce genetic mutations that can lead to cancer. The very thing that sunscreen sellers claim to protect you from. Even more incredibly, PABA is mostly inert until it becomes illuminated. Exposure to sunlight causes it to become carcinogenic. After exposure to UV radiation in sunlight, PABA or padimate-O attacks and damages DNA.

Sunscreen contains chemicals that mimic estrogen in the body – A Swiss study published in 2001 in Environmental Health Perspectives found five chemicals commonly in sunscreens that behave like estrogen. These five xenoestrogens are:

1. Octyl-1. dimethyl-PABA (OD-PABA)
2. Benzophenone-3 (Bp-3)
3. Homosalate (HMS)
4. Octyl-methoxycinnamate (OMC)
5. 4-methyl-benzylidene camphor (4-MBC)

So the result of the anti-sun campaign is this: more than half a million cases of cancer occur each year – that could have been prevented – if only a moderate exposure to sunlight had been allowed to provide normal levels of vitamin D.

Sunscreens are the Enemy, Not the Sun!

Thanks to modern day lifestyles and anti-sun propaganda message, an estimated 1 billion people worldwide are now deficient in Vitamin D. The situation is epidemic.

Not only will sunscreens NOT protect you from skin cancer, they will INCREASE your chances of getting all forms of cancer, including breast cancer, prostate cancer and lung cancer.

Optimal vitamin D levels are one of your best protections against any kind of cancer – and regular sun exposure (without sunscreen) is the best way to achieve it.

Protection by Design…

As a hormone, Vitamin D influences the entire body. Almost every type of human cell has receptors that respond to vitamin D. Which means your body is designed to make vitamin D from exposure to sunlight.

It doesn’t take a whole lot. Fifteen minutes a day or a half hour two or three times a week is enough exposure to create the Vitamin D that your body needs.  

And as long as you listen to your body’s natural messages, you will never have to worry about getting too much sun. What happens is this: depending on the amount of stress you are under, you may need just 2000 units of Vitamin D or 20,000. You can’t tell how much you need by taking your pulse or using some other artificial device. But you can tell simply by noticing that your skin feels like it has had enough.

When that happens it means your body is telling you that it has made the amount of Vitamin D that you need. Just get out of the sun at that moment and you won’t get sun burned and your immune system will be operating at full tilt.

Because vitamin D is fat soluble, it can be stored in the fatty tissues of the body. (That’s another reason it isn’t really a vitamin. It can be produced and stored naturally by the body.) But if, for some reason, a person can’t get out in the sun, he can and should supplement his intake of Vitamin D with natural foods and supplements.

How “ultra-violet” stacks up…

According to a leading vitamin D researcher, Dr. William Grant, vitamin D deficiencies cause 5 to 6 times more cancer deaths than any cancers due to excessive sun exposure.

Here’s why…

The sunlight produces two types of ultraviolet light: UV-A and UV-B.

UV-A has a longer wavelength. It is good for you. UV-B has a shorter wavelength and is bad.

Melanoma, the only type of skin cancer that can kill you, is caused by the longer wavelength ultraviolet A (UV-A).

UV-B rays stimulate Vitamin D and your immune system. They are the heroes of the cancer game. And the sun is the primary way your body gets UV-B rays.

Dr. Grant, a former NASA scientist, understood the benefit of UV-B waves. He knew that UV-B levels are measured geographically in the U.S. So he compared cancer maps with UV-B maps to see how levels of sun exposure related to cancer death rates.

What he found disproved the mythology that had been promoted for so many years by the sunscreen companies. His studies confirmed that the lower the sun exposure was, the higher the death rate was from common cancers. The final tally was this…

Premature cancer deaths due to vitamin D deficiency are 50-60,000 per year…compared to 9,800 who die of melanoma and skin cancer.

So a natural amount (15 to 30 minutes a day) of UV-B rays are healthy.

Getting the sunlight you need promotes the repair of damaged cells. This is important because damaged cells don’t repair themselves and don’t replicate. The more stress your body is subject too, the fewer healthy immune cells it has to fight cancer. Vitamin D reverses that process.

Vitamin D also helps prevent cancer cells from developing their own blood supply. This means it is harder for them to grow and spread. This suppresses metastasis.

The studies are clear about the benefits of Vitamin D and sunlight. But the government and mainstream medicine are not telling you what the studies have been saying. (Incidentally, the first study that showed the benefits of Vitamin D and sunlight dates back to an article on cancer mortality that was published in North America in 1941.)

So it’s not like the medical industry hasn’t known the facts. But they aren’t telling you. Is that because they are just plain stupid? Or might it have something to do with the billions of dollars that are made by sunscreen companies and skin doctors?

You don’t need to take a position on this question to benefit from the truth. Fear of the sun is nonsense. It is Nature’s best source of Vitamin D and Vitamin D is your body’s best protection against cancer.

If you would like to read more about the healthful benefits of the sun I can recommend this book: Your Best Health Under the Sun by Jon Herring Dr. Al Sears. Click here now for details…

Link to the original article

However, a more recent reviews have put the risk of febrile neutropenia with this regimen as high a 33%. This accords with actual clinical experience of practicing oncologists. The disrepancy seems to be explainable by the setting. In the university setting, for unclear reasons, there is less febrile nutropenia with this regimen than in the community. I therefore think that G-CSF prophyalxis is appropriate according to the NCCN and ASCO guidelines. These set G-CSF use as appropriate for febrile neutropenia risk of 20% or more.

T. Vandenberg, BA MD, J. Younus, MD, and S. Al-Khayyat, MD Febrile neutropenia rates with adjuvant docetaxel and cyclophosphamide chemotherapy in early breast cancer: discrepancy between published reports and community practice—a retrospective analysis Curr Oncol. 2010 April; 17(2): 2–3. 
However, more recent reviews have put the risk of febrile neutropenia with this regimen as high a 33%. This accords with actual clinical experience of practicing oncologists. The disrepancy seems to be explainable by the setting. In the university setting, for unclear reasons, there is less febrile nutropenia with this regimen than in the community. I therefore agree with the client's methodological point but remain of the opinion that G-CSF prophyalxis is appropraite according to the NCCN and ASCO guidelines.

T. Vandenberg, BA MD, J. Younus, MD, and S. Al-Khayyat, MD Febrile neutropenia rates with adjuvant docetaxel and cyclophosphamide chemotherapy in early breast cancer: discrepancy between published reports and community practice—a retrospective analysis Curr Oncol. 2010 April; 17(2): 2–3. 

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The test in question is actually a panel of predictive markers. They include markers that are generally accepted, for example EGFR as well as markers that are still considered experimental for decision making, such as TS, ERCC1, BRAF, KRAS.

A little clinical information about these tests based ont he information from the ResponseGenetics website:

The epidermal growth factor receptor (EGFR; ErbB-1; HER1) is a critical part of the signal transduction pathway that controls cell growth and is often over-expressed (amplified) in tumors. In a study evaluating 8 different genes as predictive factors for first-line CPT-11-based chemotherapy in colorectal cancer patients, a high intratumoral gene expression levels of EGFR was shown to be the most important factor in distinguishing responders from non-responders.

KRAS is also a part of defintion of the FDA's approval for use of Erbitux.  KRAS, a vital member of the signal transduction pathways that regulate cell growth, is often mutated in tumors. KRAS, a vital member of the signal transduction pathways that regulate cell growth, is often mutated in tumors. Mutations in KRAS gene preclude response to EGFR-directed tyrosine kinase inhibitors (TKI) but not all tumors with wild-type KRAS will respond either.The presence of KRAS mutations, which occur predominantly in patients who are current or past smokers, is strongly associated with a lack of response of CRC to the anti-EGFR antibody cetuximab. Three independent studies reported response rates of 0% to cetuximab among patients with mutated KRAS as well as shorter overall survival.

ERCC1
The enzyme excision repair complementing factor 1 (ERCC1) is part of the pathway that repairs DNA damage caused by platin therapy. Low ERCC1 has consistently been found in several retrospective studies to be a favorable indicator for response of tumors and/or improved survival after platinum therapy while high ERCC1 expression is associated with resistance to platinum therapy and shorter survival in many cancer types including gastric, ovarian, bladder, head-and-neck, non-small cell lung, esophageal and colorectal. In a study of advanced colorectal cancer study treated with 5-FU/oxaliplatin,1 low ERCC1 mRNA expression levels were significantly associated with longer survival. In contrast to oxaliplatin regimens, high expression of ERCC1 was correlated with response to irinotecan therapy.

TS
Thymidylate synthase (TS) is a growth rate-limiting enzyme of DNA synthesis. TS expression is a predictor of response to 5-fluorouracil (5-FU), which for over 50 years has been a mainstay of chemotherapy of colorectal cancer (CRC). Many studies have agreed that high levels of TS are associated with resistance of tumors to 5-FU and its derivatives, even when used in combination with other agents such as oxaliplatin (the FOLFOX regimen).

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Is the entire panel med. necessaryl? Since the EGRF and KRAS on the panel are medically necessary, I consider the entire test medically necessary. Insureres  may consider negotating the total price for the panel based on the two medically necessary components.

nccn.org, colon cancer

prescribing information, Erlotinib

http://www.responsegenetics.com/genes#colon

Link to the original article