Traditional cancer treatment like standard Maximum Tolerated Dose (MTD) chemotherapy has always horrified me. These methods are highly toxic and often cause tremendous side effects and suffering. I have known close relatives and friends whose immune systems were so devastated by traditional aggressive chemotherapy and radiotherapy that they died of maladies like fever and flu just months after they were declared to be in remission from their cancer.

In MTD chemo, high doses of cytotoxic drugs – the highest doses possible without causing life-threatening levels of toxicity – are administered intravenously to cancer patients. Because it is very toxic to the body, MTD chemotherapy requires prolonged breaks (generally of 2-3 weeks in duration) between successive cycles of therapy. This gives the cancer an opportunity to recover and re-establish itself. This is why cancer cells often seem to quickly become resistant to MTD chemotherapy.

Recently, I learned about a gentle form of chemotherapy with virtually no side-effects called metronomic chemotherapy. Unlike MTD chemotherapy, metronomic chemotherapy involves taking low-dosage cytotoxic drugs orally – in tablet form – usually daily over a prolonged period, without the breaks necessitated by MTD chemotherapy.

Chemotherapy drugs are designed to inhibit or kill cancer cells by damaging DNA. However, cells can employ a number of mechanisms to repair this damage. When cells experience drug-induced breaks in their DNA strands, proteins called PARPs bind to the DNA at the sites of the breaks and recruit other proteins involved in DNA repair. This process can allow cancer cells to continue to survive and grow despite the damage caused by chemotherapy treatment.

With metronomic chemotherapy, the low-dose chemo drugs are administered regularly, without missing a beat, like the rhythmic beat of the metronome. Hence, the cancer is given little time to repair and restore itself, while toxicity and side effects are kept minimal.

Dr. Harold J. Burstein of the Dana-Farber Cancer Institute, who has led several early-stage trials of metronomic chemotherapy in women with breast cancer elucidates that “… metronomic chemotherapy …refers to repetitive, low doses of chemotherapy drugs designed to minimize toxicity and target the endothelium or tumor stroma as opposed to targeting the tumor”.

Low, non-toxic doses of chemotherapy drugs, when delivered frequently for a prolonged period of time, can retard tumor blood vessel growth (or angiogenesis) by destroying endothelial cells. Evidence is growing that more compressed or accelerated schedules of drug administration using much smaller individual doses than the MTD can be more effective in controlling tumor growth, and stabilising the patient’s condition for a longer period of time.

Angiogenesis is the creation of new blood vessels from an existing blood vessel – such as from established blood vessels to a tumor – and tumors use this source of nutrition to grow. This vascular structure is the target of drugs like Avastin. Endothelial cells form the lining of newly-formed blood vessels. Standard MTD chemotherapy destroys the endothelial cells in the small blood vessels but in the usual 2 – 3 weeks pause given before the next chemotherapy session, the blood vessel grows into the cancer again.

On February 23rd 2008, at the 28th annual German Cancer Congress, cancer researcher D. McDonald from San Francisco presented a lecture at a symposium entitled: “Anti-angiogenesis, Therapy for Solid Tumours”. McDonald showed pictures from his research and demonstrated that just one day after anti-angiogenesis treatment was stopped, the endothelial cells start sprouting and sending out growth processes from the basal membrane. One week from stopping the anti-angiogenesis treatment, the blood vessels and the blood supply to the cancer tumor – the tumor’s vascular system – are fully re-established.

The metronomic approach was initially proposed and tested in animal models by Dr. Timothy Browder in Dr. Judah Folkman’s lab at Harvard Medical School. The studies recorded that standard MTD chemotherapy regimens caused cell death of endothelial cells in the blood vessels feeding to the tumor first, followed by tumor cells. However, the long breaks needed between the MTD regimens allowed the damaged blood vessels, and thus the tumor, to recover.

On the other hand, significantly lower doses given more frequently on a prolonged schedule proved to be far more effective, including complete tumor regressions, even in mice that were resistant to the same drug when used in a standard MTD regimen.

Various other research groups have confirmed these findings. Further, studies conducted in cell lines and animal models have reported that combining metronomic chemotherapy with targeted anti-angiogenesis agents seems more effective than metronomic chemotherapy alone.

Italian oncologists documented the long-term responses of patients with metastatic breast cancer to a metronomic regimen involving daily cyclophosphamide (50mg) and two weekly doses of methotrexate (5mg per dose)). 32% achieved either a complete or partial remission, or a stabilization of disease lasting at least 24 weeks. In about 16% of patients, no tumor progression was noted for over a year. Even in the patients in whom progression did occur, it was believed that the therapy slowed the spread of the disease.

As metronomic therapy is directed against endothelial cells, not cancer cells, a metronomic regimen that works well with one type of cancer should work with all types of cancer dependent on angiogenesis for growth.

A well-documented case study of a 36-year old patient with advanced epithelial ovarian cancer who had responded poorly to standard MTD chemotherapy reported that she performed well on metronomic chemotherapy. She went on to live a normal working and social life for five more years, without side effects.

A major benefit of metronomic chemotherapy is that it is essentially free of harmful side effects. Only a mild suppression of white cell count was observed in a small minority of the treated patients.

Yet another interesting benefit of metronomic chemotherapy is that it selectively kills a type of immune cell – T-reg cells – that function to suppress the activity of immune cells capable of attacking the tumor – the natural killer (NK) cells and T-cytotoxic cells. T-reg cells are often found within tumors and secrete hormone-like factors that “turn off” the immune cells trying to attack the cancer. Metronomic chemotherapy is therefore a useful adjuvant to therapeutic strategies intended to boost the tumor-killing capacity of NK and T-cytotoxic cells.

For people dealing with cancer, especially those adverse to aggressive cancer treatment, and particularly those for whom traditional MTD chemotherapy has failed, metronomic chemotherapy is good news. Those seeking a gentler, less-aggressive and less-harmful form of cancer treatment at least now have this option to explore.

In a 2010 ASCO (American Society of Clinical Oncology) report, promising results from administering metronomic chemotherapy with capecitabine to heavily pretreated patients with metastatic breast cancer – including those with HER2 positive breast cancer – were reported. This offers hope even to those with advanced breast cancer for whom standard aggressive cancer treatment like MTD chemotherapy has failed.

Of course, some people feel that metronomic chemotherapy may work too slowly for those with clearly progressive cancer. A hybrid approach may be the answer. In a phase III clinical trial which involved women with locally advanced or inflammatory breast cancer, a presurgical (or neoadjuvant), metronomic-like regimen – using higher doses of cyclophosphamide, given daily; doxorubicin; and growth factor support to ensure the continued production of white blood cells – was found to be superior to a standard MTD regimen at eliminating evidence of invasive cancer at the time of surgery.

This outcome, explained Dr. Robert Livingston, a co-investigator on the Southwest Oncology Group-led trial, generally has been found to predict superior long-term outcome in patients. The idea was to try to expose tumor cells to minimum concentrations of chemotherapy drugs for as long as possible.

“I think it’s fair to call the regimen we have developed a hybrid,” said Dr. Livingston. “It can destroy tumor cells and, at the same time, the continuous exposure, particularly to cyclophosphamide, is having an anti-angiogenic effect.”

The hybrid metronomic regimen delivers chemotherapy more frequently, even daily, at significantly higher doses than those used in most metronomic regimens but less than in MTD regimens. The toxicity might be greater than a “traditional” metronomic regimen, but so might the effectiveness.

If you’re looking for a gentler, less toxic and relatively safe form of chemotherapy, talk to your oncologist or check with your nearest cancer center. Clinical trials utilizing metronomic chemotherapy are also ongoing.

Posted: July 5th, 2010 under Alternative Remedies, Cancer.
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For years I ignored it because I didn’t know what it was. There were usually several varieties available on the supermarket shelves, and in the Chinese medicinal shops it was available as dried herbs, granules as well as pills or capsules. Then recently, for some reason, I started researching it. What I found out spurred me to stock my larder with products containing it.

The oldenlandia plant has been used by the Chinese for medicinal purposes for centuries. The book “An Illustrated Guide to Antineoplastic Chinese Herbal Medicine” lists oldenlandia as having the following:

Properties: sweet, bland, slightly bitter, and slightly cold. Clears heat and toxin, activates blood circulation, removes blood stasis, promotes diuresis, and relieves stranguria (urinary obstruction).

Indications: various kinds of tumor, especially tumors of the digestive tract, lymphosarcoma, carcinoma of the liver and larynx. Also for appendicitis, hepatitis, pneumonia, cholecystitis, urinary infection, furunculosis, cellulites, and snake bite.

In an article titled “Oldenlandia and Scutellaria: Antitoxin and Anticancer Herbs” by Subhuti Dharmananda, Ph.D., Director, Institute for Traditional Medicine, Portland, Oregon, USA, it is said that the oldenlandia is from the Rubiaceae family, and is collected from the wild. It is found mainly in the southeastern provinces of China-Guangxi, Guangdong and Fujian-growing at low altitude in moist fields. According to Dr. Dharmananda, Dr. Jiao Shude, in his “Ten Lectures on the use of Medicinals”, says that he “frequently adds about 30-40 grams of this medicinal to an appropriate decoction medicine devised according to the principle of pattern identification” for treating various forms of cancer. He also suggests adding some other anticancer herbs, such as scutellaria.

In “Pharmacology and Applications of Chinese Materia Medica”, it states that: “The herb at the dose of 30-60 grams is often added to conventional prescriptions for carcinoma.” In “Chinese Medicinal Herbs of Hong Kong”, among the indications for oldenlandia is “early stage of cancer of lungs, liver, and rectum.” It is recommended there that oldenlandia be used in a dosage of 60 grams along with 30 grams of scutellaria as a decoction, taken once a day.

Various laboratory studies of the action of oldenlandia suggest that the herb may contribute to inhibiting growth of cancer cells, promoting cancer cell death (apoptosis), and enhancing immune attack against cancer cells.

In the 2006 report “Evidence for Oldenlandia diffusa-evoked cancer cell apoptosis through superoxide burst and caspase activation” by Yadav SK and Lee SC from the Yong Loo Lin School of Medicine, National University of Singapore, Singapore, the researchers concluded that “the ethanol extract of the herb effectively evokes cancer cell apoptosis, possibly through burst-mediated caspase activation.” This study was published in PubMed.gov, the online publication of the U.S. National Library of Medicine, National Institutes of Health

In another study, the “Apoptotic effect of Oldenlandia diffusa on the leukaemic cell line HL60 and human lymphocytes”, published in the Journal of Ethnopharmacology, Volume 114, Issue 3, 3 December 2007, the researchers reported that their findings“support a cytotoxic action for Oldenlandia diffusa”

Oldenlandia may be used as a preventive health care agent to inhibit mutation of cells by carcinogens. As it also builds up the immune system, this herb may be beneficial for anyone undergoing modern cancer therapies. Fortunately for me, oldenlandia diffusa grows wild here and beverages containing oldenlandia are cheap (the equivalent of 50 US cents per bottle) and easily available where I live. I particularly like one from China which is a sparkling mineral water with oldenlandia extract. It comes in a green glass bottle and the Chinese have been drinking it for decades. You can probably find oldenlandia beverages in most Asian supermarkets and grocers as well as Chinese medical shops.

In Chinese, oldenlandia diffusa is known as “baihuasheshecao” (sometimes written Bai Hua She She Cao). “Baihua” means white flower, “she” means snake, and “shecao” means tongue weed, referring to the long thin leaves of the herb. English-speakers sometimes refer to it as the snake-needle weed.

Cheers to good health!

Posted: June 22nd, 2010 under Cancer, Healing Foods, Health Supplements, Immune System Health.
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I got really excited recently when I read that oncology researchers have reported that extra-virgin olive oil is an effective anti-cancer fighter against an aggressive form of breast cancer, HER2 breast cancer. According to the Mayo Clinic, “HER2-positive breast cancer is a breast cancer that tests positive for a protein called human epidermal growth factor receptor 2 (HER2), which promotes the growth of cancer cells. In about 1 of every 5 breast cancers, the cancer cells make an excess of HER2 due to a gene mutation. This gene mutation and the elevated levels of HER2 that it causes can occur in many types of cancer — not only breast cancer…..HER2-positive breast cancers tend to be more aggressive than other types of breast cancer. They’re also less responsive to hormone treatment.”

HER2 positive breast cancer is one of the most frightening breast cancers to deal with and the drug which is typically used to treat it – Herceptin – is very expensive. So the news that phytochemicals in extra-virgin olive oil – an affordable, easily obtainable and harmless food – can shrink certain breast tumors should give hope to many.

The extra-virgin olive oil study was performed at the Catalan Institute of Oncology in Girona, Spain, and reported in the open-access journal BMC Cancer. It focused on tumor tissue in laboratory culture that the researchers exposed to different fractions of extra-virgin olive oil containing various natural phytochemicals. When rats with induced breast cancers were fed large amounts of extra-virgin olive oil, their tumors’ malignancy diminished.

“Our findings reveal for the first time that all the major complex phenols present in extra-virgin olive oil drastically suppress overexpression of the cancer gene HER2 in human breast cancer cells,” said Javier Menendez, who, along with Antonio Segura-Carretero from Spain’s University of Granada, led the team of researchers who determined to investigate which parts of extra-virgin olive oil battle cancer best.

Some past studies have suggested that the olive-oil-rich Mediterranean diet prevents cancer, while other studies have not. So the Spanish scientists theorized that olive oil compounds kill only certain forms of breast cancer. Their research found that the olive-oil polyphenols known as secoiridoids and lignans are highly effective breast-cancer-cell fighters – but only against the 20 percent to 30 percent of breast cancers that express the so-called HER2 gene.

Extra-virgin olive oil comes from pressing olives in a cold state – without the use of heat or chemicals. It contains natural complex anti-cancer chemicals that the industrial refining process destroys. So will eating large quantities of such olive oil actually prevent or cure breast cancer? Sadly, the authors note that “The active phytochemicals exhibited tumoricidal effects against cultured breast cancer cells at concentrations that are unlikely to be achieved in real life by consuming olive oil.”

Still, the scientists say, “These findings, together with the fact that that humans have safely been ingesting significant amounts of lignans and secoiridoids as long as they have been consuming olives and extra-virgin oil, strongly suggest that these polyphenols might provide an excellent and safe platform for the design of new anti breast-cancer drugs.”

I don’t know about you, but I’m still going to add more extra-virgin olive oil to my salads.

Posted: June 19th, 2010 under Alternative Remedies, Cancer, Healing Foods.
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