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Tuesday, September 23, 2008

Clots and Cancer Care

One of the serious side effects of chemotherapy is severe nutritional depletion. This state is a factor in the 20% or more of people undergoing mainstream cancer therapy.

I would like to know how many people undergoing chemo know of this side effect, and of course I'd like to know how many of this group of people have support to promote prevention of this life-threatening risk.

Vitamin E is a preventive for colon cancer and most likely other cancers. It helps prevent hair loss from chemo, and it helps prevent throboembolic conditions.

As an anti-oxidant it is an anti-inflammatory, so one might surmise that it could/would be effective as a standard supplement for cancer treatment to reduce the side effects of the chemo drugs that must irritate the intima or lining of the blood vessels that contribute to an increased risk of developing VT.

Adding vitamin C can offer similar benefit, and it can fight the cancer as well, perhaps allowing a lower chemo dose with greater effect.
Should All Cancer Patients Receive Antithrombic Prophylaxis?

Roxanne Nelson, Medscape Medical News 2008. © 2008 Medscape

September 23, 2008 (Stockholm, Sweden) — Venous thromboembolism (VTE) is a common complication in cancer patients, and a significant cause of morbidity and mortality. It occurs in approximately 4% to 20% of cancer patients, although it is believed that these rates are underestimates. Although randomized trials have demonstrated that primary prophylaxis can reduce VTE, and professional guidelines from several associations have issued a number of recommendations, there is still considerable variation among practicing oncologists in terms of compliance.

Because the risk for VTE is so high among cancer patients, some experts believe that VTE prophylaxis should be extended to all cancer patients, including those in the outpatient setting. Conversely, others feel that there is insufficient evidence to support universal use in this population and that prophylaxis should be administered only to those with known risk factors. Both sides of the issue were presented here in a point/counterpoint discussion at the 33rd European Society of Medical Oncology (ESMO) Congress.

Hans-Martin Otten, MD, PhD, who presented the argument for the use of prophylaxis in all cancer patients, pointed out that VTE remains underdiagnosed and undertreated in cancer patients. Dr. Otten is a medical oncologist at Slotervaart Hospital, in Amsterdam, the Netherlands.

"There's a very high prevalence of VTE among cancer patients," said Dr. Otten. "In most cases, it is not recognized. There is effective prophylactic treatment. It is low in cost and low in bleeding risk, so why don't we use it?"

Use in Surgical and Hospitalized Patients

Current guidelines from the American Society of Clinical Oncologists (ASCO) recommend that cancer patients undergoing major surgery, along with hospitalized nonsurgical cancer patients, should be considered candidates for VTE prophylaxis in the absence of bleeding or other contraindications. Guidelines from the American College of Chest Physicians also recommend prophylaxis for bedridden patients with cancer.

Dr. Otten agrees: "Pulmonary embolism [PE] is a frequent cause of death in hospitalized patients, and 1 of the primary reasons for promoting antithrombic prophylaxis in high-risk patients," he said. "The in-hospital fatality rate from PE is about 12%. And not only are fatal PEs important, but symptomatic VTE is a burden for cancer patients."

Presenting the opposing viewpoint, Ajay Kakkar, MBBS, PhD, FRCS, agreed that there are a number of situations where the use of antithrombotics is warranted, especially among cancer patients undergoing surgery. Dr. Kakkar is professor and head of the Centre for Surgical Science and dean of external relations at Barts and the London School of Medicine and Dentistry, in the United Kingdom

"VTE is a very common problem for surgical cancer patients, and there are really hard data to support prophylaxis," explained Dr. Kakkar.

However, the data for other types of cancer patients are less robust. Among nonsurgical hospitalized cancer patients, there is a wide range of VTE incidence. "It is therefore inappropriate to offer all patients prophylaxis," said Dr. Kakkar. "We should identify the subsets that may be at risk and treat them."

He pointed out that the data on VTE risk in nonsurgical cancer patients are limited. Although studies have shown a clear benefit of prophylaxis over placebo, only a small number of the patients included in these trials have had cancer. "Results can be extrapolated for cancer patients," Dr. Kakkar said, "but right now we just don't have the information."

Although guidelines do recommend that nonsurgical hospitalized patients should be considered candidates for prophylaxis, Dr. Kakkar explained that physicians need to be selective in choosing who is at risk.

Ambulatory Outpatients

ASCO guidelines do not recommend routine prophylaxis in ambulatory patients receiving chemotherapy because of conflicting trial results, potential bleeding, the need for laboratory monitoring and dose adjustment, and the relatively low incidence of VTE.

However, Dr. Otten argued that prophylaxis should be extended to this population as well. VTE is poorly recognized and, in about 70% to 80% of patients who die in the hospital, a diagnosis of PE was never considered, he explained. "The majority of symptomatic PE occurs after discharge, in the outpatient setting, where doctors do not see patients very frequently."

Some reports show that the incidence of symptomatic VTE in patients with advanced metastatic disease is 9%, said Dr. Otten. "But the rate of asymptomatic VTE is more than 50%."

Conversely, Dr. Kakkar felt that routine prophylaxis is not warranted in this population, and supported current guidelines. The risk for VTE among patients undergoing outpatient chemotherapy is not well studied, and the overall risk is not high, he said. "I believe it is a question of our judgment and skills to select patients, rather than to prescribe it routinely to ambulatory patients.

Complicated Issue; Very Heterogenous Patients

"This is a complicated issue, but it is clear that cancer patients as a whole have a much higher risk than the general population," commented Alok A. Khorana, MD, FACP, assistant professor of medicine at the James P. Wilmot Cancer Center at the University of Rochester, in New York. "But this population is also very heterogenous, and the risk is not equally divided," he commented in an interview..

"Some patients are at much higher risk than others, and the main problem is that no studies have been done specifically in cancer populations," he said. Dr. Khorana did not participate in the ESMO point/counterpoint discussion; he was approached by Medscape Oncology for comment.

The exact mechanisms of VTE in cancer patients are still being defined, and the actual prevalence of tumor-induced VTE is not known, he said. There are numerous confounding risk factors, including chemotherapy with or without adjuvant therapy, immobilization, metastatic disease, surgery, tumor type, presence of certain comorbidities, and the presence of central venous catheters.

Dr. Khorana agreed that although ambulatory patients on chemotherapy are at higher risk for VTE, the risk does vary. "There are subgroups that are at higher risk because of the type of cancer and other comorbidities, and it is important to focus on the high-risk subgroups," he told Medscape Oncology.

To help identify that population among ambulatory patients, Dr. Khorana and colleagues developed a simple model for predicting chemotherapy-associated VTE, using baseline clinical and laboratory variables. A risk model was derived and validated in an independent cohort of 1365 cancer patients, and the results showed that it was able to identify patients with a nearly 7% short-term risk for symptomatic VTE. The data were published in the May 15 issue of Blood.

Prolonging Survival

An unanswered question is whether the use of antithrombotic therapy can prolong survival in cancer patients without VTE. There have been a few trials that did suggest a survival benefit, said Dr. Kakkar. Although some results have been encouraging, the results are variable and generally showed a clinical benefit only in subgroup analyses.

"More concise data are needed, and it is not possible now to make recommendations," said Dr. Kakkar.

33rd European Society for Medical Oncology (ESMO) Congress. Presented September 14, 2008.

Blood. 2008;111:4902-4907. Abstract


Dr. Art Ayers said...

I agree with all of your comments. I am a retired molecular biologist interested in heparin/inflammation interactions. I see VTE as a result of inflammation based decrease in systemwide heparin production. Cancer is also based on inflammatory signaling via NFkB. So it would seem to make sense that treatment with heparinoids would lower inflammation, lower the risk of VTE and also attack the cancer.
As you also point out diet and impact on gut flora is another big issue. These patients, by being is intimate association with health care practitioners and compromising medications, would be expected to have highly inflammatory get flora and associated problems with nutrient uptake. This will lead to lots of problems with oxidative stress (low B12 C and methionine leading to low glutatione).
Thanks for your insights.
Here is my blog on related subjects:

herbalYODA said...

Thank you for your comments. I'd like to add that you may have an interest in this information, relevant to your work:, and the several posts I have on B12.