Archive for February, 2008
By M Zhang, X Liu, J Li, L He, D Tripathy
Cochrane Database of Systematic Reviews 2008 Issue 1
Date of Most Recent Substantive Amendment: 18 February 2007
Abstract
Background
Short term side-effects of chemotherapy include fatigue, nausea, vomiting, mucositis and myelosuppression or neutropenia. These occur during the course of treatment and generally resolve within months of completion of chemotherapy. A variety of Chinese medicinal herbs have been used for managing these side effects.
Objectives
To assess the effectiveness and safety of Chinese medicinal herbs in alleviating chemotherapy-induced short term side effects in breast cancer patients.
Search strategy
We searched The Cochrane Breast Cancer Specialised Register (15/02/2007), The Cochrane Central Register of Controlled Trials (CENTRAL); (The Cochrane Library 2006, Issue 4); MEDLINE (1966 to December 2006); EMBASE (1990 to December 2006); and Chinese Biomedical Literature (2006, Issue 4). A number of journals were hand searched.
Selection criteria
Randomised controlled trials comparing chemotherapy with or without Chinese herbs in women with breast cancer.
Data collection and analysis
Two authors independently extracted the data, which were analysed using RevMan 4.2. For dichotomous data, we estimated the relative risk. For continuous data, we calculated the weighted mean difference.
Main results
We identified seven randomised controlled trials involving 542 breast cancer patients undergoing or having recently undergone chemotherapy. All studies were conducted and published in China. We did not pool the results because few studies were identified and no more than two used the same intervention. All were of low quality and used CMH plus chemotherapy compared with chemotherapy alone.
CMH combined with chemotherapy showed no statistically significant difference for the outcomes of phlebitis and alopecia. Only one study showed an improvement in nausea and vomiting, and in fatigue. Three indicated an improvement in white blood cells in the group receiving CMH. Two showed an increase in percentage changes in T-lymphocyte subsets CD4 and CD8. One study showed a statistically significant difference for CMH in percentage changes in T-lymphocyte subsets CD3, CD4 and CD8. Two herbal compounds may have improved quality of life. One study reported that CMH may have some effect on reducing toxicity in liver and kidney, but differences were not statistically significant.
Authors’ conclusions
This review provides limited evidence about the effectiveness and safety of Chinese medicinal herbs in alleviating chemotherapy induced short term side effects. Chinese medicinal herbs, when used together with chemotherapy, may offer some benefit to breast cancer patients in terms of bone marrow improvement and quality of life, but the evidence is too limited to make any confident conclusions. Well designed clinical trials are required before any conclusions can be drawn about the effectiveness and safety of CHM in the management of breast cancer patients.
Plain language summary
Chinese medicinal herbs for the treatment of side-effects from chemotherapy in breast cancer patients
Chinese medicinal herbs (CMH) include any mixture of herbal compounds and decoction (the process by which herbs are boiled and remaining liquid used for health purposes), including the development of herbal formulae and injections, and capsules. Although CMH are used to counteract the side effects of chemotherapy (cancer treatment with chemical agents that are selectively destructive to malignant cells and tissues) in patients being treated for cancer, the evidence for their use for women with breast cancer has not been ascertained. The purpose of this systematic review was to evaluate the effectiveness and safety of CMH in alleviating chemotherapy-induced short term side effects for women either undergoing chemotherapy or having recently undergone chemotherapy. Short term side effects are those that occur during the course of the treatment and generally resolve within months of the completion of the therapy and affect up to 60% of patients.They include nausea and vomiting, mucositis (inflammation of the mucous membranes lining the digestive tract from the mouth down to the anus caused by chemotherapy); neutropenia (a decrease in white blood cells caused by chemotherapy); myelosuppression (a condition in which bone marrow activity is decreased, resulting in fewer red blood cells, white blood cells, and platelets), and fatigue (loss of energy and tirdness). This review found seven randomised studies involving 542 breast cancer patients addressing this question. These studies used six different herbal remedies to treat the side effects of chemotherapy, all used CMH plus chemotherapy as the intervention compared with chemotherapy alone. The results suggest that using Chinese herbs in conjunction with chemotherapy or CHM alone may be beneficial in terms of improvement in marrow suppression and Immune sytstem, and may improve overall state of quality of life. However, further trials are needed before the effects of TCM for people with breast cancer can be evaluated with any real confidence.There was no evidence of any harms of CMH.
February 26th, 2008
Survival in advanced cancer patients is directly related to nutritional status, and this (as well as immune status) can be influenced by administration of fish oil together with vitamin E. This is the conclusion of Greek research just published in the journal “Cancer”.
The researchers studied a group of 60 patients with advanced, generalised solid tumours, which were felt to be no longer responsive to conventional treatment.
The cancer patients were randomised into intervention and placebo groups, with a further control group of 15 healthy patients. In each cancer group there were an equal number of adequately nourished patients and malnourished patients (as judged by a combination of weight loss >10%, serum albumin <30 g/L, serum transferrin <2.0 g/L and Karnofsky performance status <60) .
Intervention: consisted of daily fish oil (18 capsules of MAXEPA each containing 170 mg EPA/115 mg DHA) together with 200 mg of vitamin E. Nutritional status and immune function were measured before and during intervention. Immune assessment included T cell sub-sets and cytokine
production.
Results: Prior to treatment, the ratio of T-helper cells to T-suppressor cells was significantly lower in malnourished cancer patients compared to well nourished ones. This was considerably improved after fish oilsupplementation (see table 1).
Table 1: CD4/CD8 ratio before and after fish oil/vitamin E supplementation
ACTIVE PLACEBO Signif.
Well n. Maln. Well n. Maln. (Well n. vs Maln.)
————————————————————————————————–
Before 1.75 1.21 1.82 1.23 p<0.05
Day 40 2.03 1.84 1.79 1.19 NS
————————————————————————————————–
p value NS 0.05 NS NS
(pre vs post)
Initially malnourished patients survived for a mean period of 213 days (±19), compared with 481 days (±35) for initially well nourished patients.
The most interesting finding was that the combined group of supplemented patients – both those who were initially well nourished and those who were malnourished – had a significant increase in survival compared with the placebo patients (p < 0.025: see table 2).
The longest survived group was the initially well-nourished patients who received the supplementation, whilst the shortest survived group were the initially malnourished patients who were given placebo.
Table 2: Patient cumulative survival
Suppl. Placebo
————————————————-
Day 180 75% 50%
Day 240 65% 30%
Day 360 55% 25%
p<0.025
(NB: values above are approximate and estimated from the graph in the original paper)
Ref: Cancer 82:395-402, 1998
February 26th, 2008
Serum levels of androgens and oestrogens were not related to risk for developing prostate cancer in initially healthy men.
During the past several decades, many hypotheses about prostate cancer etiology have gained wide support, including family history, genetics, and consuming a Western diet. Elevated androgen levels have long been considered a likely risk factor, and many studies have been conducted in an attempt to characterize this attribute. For example, the Prostate Cancer Prevention Trial (PCPT) — the results of which demonstrated a 25% lower rate of prostate cancer in men who were randomized to receive the 5-reductase inhibitor finasteride — was designed, in part, to determine whether elevated androgen levels were associated with higher risk for developing disease (N Engl J Med 2003; 349:215).
In an unusual research effort, investigators who had published prospective studies on prostate cancer risk and endogenous sex hormone concentrations were invited to join a collaborative group. Most investigators who were contacted agreed to participate; data were contributed from 18 prospective studies (3886 men with prostate cancer and 6438 controls), which represented 95% of data available worldwide. In these studies, blood samples were collected from healthy men who were then followed to identify those who developed prostate cancer. Laboratory analyses were performed on blood samples from patients with incident prostate cancer and from matched control subjects. Data, including patient characteristics and all lab variables, were analyzed in a conditional logistic regression that was stratified by study, age at recruitment (2-year age bands), and date of recruitment (single year).
No significant associations were found between serum concentrations of any androgen or estrogen and risk for prostate cancer. Additionally, no association was noted between risk for prostate cancer and concentrations of androstanediol glucuronide, androstenedione, dehydroepiandrosterone sulfate, estradiol, or free estradiol. Levels of sex-hormone binding globulin were significantly and inversely related to prostate cancer risk. No interstudy heterogeneity was found in the estimated trends for any hormone, and adjustment for potential confounders did not affect risk estimates.
Comment: The findings from this impressive collaborative effort provide an important addition to our understanding of prostate cancer aetiology. As editorialists note, “By confirming the lack of evidence to support an androgen–prostate cancer hypothesis, the study obliges the scientific community to move past a seductive, clinically relevant, and biologically plausible hypothesis and get on with the difficult task of exploring, analyzing, and characterizing modifiable risk factors for prostate cancer.”
Published in Journal Watch Oncology and Haematology February 19, 2008
February 20th, 2008
Older men with early-stage prostate cancer are not taking a big risk if they keep an eye on the disease instead of treating it right away, suggests the largest study to look at this issue since PSA tests became popular.
Only 10 percent of the 9,000 men in the study who chose to delay or skip treatment had died of prostate cancer a decade later. The vast majority were alive without significantly worsening symptoms or had died of other causes.
Even the 30 percent who eventually sought treatment were able to delay it for an average of 11 years.
“It is important news,” said Dr. Otis Brawley, chief medical officer of the American Cancer Society. “It may persuade some middle-of-the-roaders that we are overtreating this disease,” and that PSA testing may be amplifying the problem, he said. The PSA blood test to help detect tumors has been widely used since the 1990s.
Grace Lu-Yao of Robert Wood Johnson Medical School in New Jersey led the study and will report results at a cancer conference later this week in San Francisco.
Whether to treat prostate cancer is one of the biggest medical dilemmas today. The disease is the most common cancer in American men – about 220,000 cases will be diagnosed this year – but most tumors grow so slowly they never threaten lives. There is no sure way to tell which tumors will.
PSA tests can help find tumors many years before they cause symptoms, but routine screening of men at average risk of the disease is not recommended, because there is no proof it saves lives.
Prostate cancer treatments are tough, especially on older men. Many men are left with sexual or bladder control problems. Some doctors instead recommend “watchful waiting” to monitor signs of the disease and treat only if they worsen, but smaller studies have given conflicting views of the safety of that approach.
The new study looked at the natural course of the disease in men who chose that option. It is the first involving so many older men – half were over 75 – and so many whose tumors were found through PSA tests.
Using the federal government’s cancer database, researchers studied 9,018 men diagnosed from 1992-2002 with early-stage prostate cancer who did not get surgery, radiation or hormone therapy for at least six months. Most never got any treatment at all.
A decade later, 3 percent to 7 percent of those with low- or moderate-grade tumors (rated by how aggressive the cells appear) had died of prostate cancer, versus 23 percent of those with high-grade tumors. Overall, prostate cancer killed 10 percent of them.
“The great majority of patients … are going to die of something else,” so most older men with early-stage tumors could delay treatment, Lu-Yao said.
“If people are younger or have more advanced disease, I wouldn’t say this is a safe option,” but most cases are diagnosed in men 68 or older, and most are early stage, she noted.
The National Cancer Institute paid for the study. It is not the final word – that usually comes from studies where similar groups of patients are randomly assigned to get one treatment or another, and the results compared. But absent that kind of evidence, this large study “does show that a large number of men do well with no initial treatment and indeed with no treatment long term,” Brawley said.
Dr. Howard Sandler, a radiation and prostate specialist at the University of Michigan, agreed, but cautioned, “there are exceptions to every rule,” and some very active, healthy older men may do better having treatment right away, along with older men who have higher-grade tumors.
Earlier this month, a scientific review published in the Annals of Internal Medicine concluded that evidence was too thin to recommend treatment over watchful waiting, or one treatment over another. Studies do show that prostate cancer surgery mostly helps men under 65, said Dr. Timothy Wilt of the Minneapolis VA Center for Chronic Disease Outcomes Research, who led the review.
The new study shows that for men older than that, “observation is a very reasonable approach,” he said. “Many men do quite well for a long period of time with no treatment.”
The cancer conference is sponsored by the American Society of Clinical Oncology and several other groups.
Although routine PSA testing is not recommended for all men, the cancer society does advise giving men information and the option to have it starting at age 50. Screening is recommended starting at age 45 for men with a family history of prostate cancer and for black men, because of their higher risk of the disease.
February 17th, 2008
ALMOST 3000 men die of prostate cancer each year in Australia and an estimated 18,700 are diagnosed with the disease. With baby boomers now reaching their 50s and 60s, those figures are set to increase.
So, is enough being done to reduce the emotional toll that surgery can take on men?
Not surprisingly, sexual dysfunction tops the list of the most common post-operative side effects that men complain about in a study published in a recent issue of Urologic Nursing.
Significantly, it is urinary dysfunction issues that are troubling men most and many are not emotionally prepared for these complications, says lead author Bryan Weber, assistant professor in the University of Florida College of Nursing.
Professor Weber said, given the various treatment options for prostate cancer, men who undergo radical prostatectomy might initially decide the risk of physical dysfunction was worth the benefit of improved survival. However, many did not know what to expect in the months after surgery.
“The effects of this treatment are quite immediate and can lead to depression and frustration,” she said.
The authors evaluated 72 men six weeks after they underwent prostatectomy, measuring their physical function and assessing whether they had urinary, bowel and sexual dysfunction. Measurement of self-confidence, social support and uncertainty about their disease and treatment were also recorded.
“Almost immediately after treatment, men may experience depression, awkwardness and emasculation, which will have a great effect on their quality of life.”
Over half the men reported low to moderate social support, indicating that many of the topics proved embarrassing for them to discuss with others. The level of social support was significantly related to urinary problems, revealing those with incontinence may need additional support compared to those with greater bladder control.
Asked by Consult if greater access to formal counselling services was needed for this group of patients, Professor Weber agreed.
“Yes – men have indicated that little information is provided pre and post surgery that highlights available options in dealing with treatment side effects.
“After an initial diagnosis of prostate cancer, men may be so focused on eradicating the disease that they don’t realise the effects the treatment will have on their quality of life, both for them and their families.”
Physical side effects of prostate cancer treatment limit daily activities and may interfere with a man’s sense of masculinity and self-confidence. Urinary incontinence requires the use of pads which can create concern about leakage and odour, Professor Weber said.
“Sexual dysfunction interferes with a man’s sense of self and may limit the relationship he has with his significant other.”
Professor Weber suggests clinicians assess men and their support systems, identify changes in physical function that may occur as a result of treatment and direct them to products and services designed to help them cope with the immediate effects of sexual dysfunction and urinary and bowel incontinence.
Men also need to be made aware of the numerous medications to ease sexual dysfunction, their cost and potential side effects.
“Education and counselling should be provided to these men to better inform and prepare patients for the physical side effects they are likely to experience postoperatively.
“Since we know that men are less likely to rely on support groups or be more embarrassed to discuss these items with family and friends, it’s even more vital for health-care professionals to stress these issues and include options for patients.
“Men need to be introduced to different options, make choices and regain control over their lives.”
Source
Urologic Nursing
February 7th, 2008
An important paper on the interaction of antioxidants and radiation therapy was recently published in the International Journal of Cancer. Interestingly, despite the significance of its findings, this study has received virtually zero attention from the scientific community or the media.
As background, in April 2005, Isabelle Bairati, MD, PhD, and her colleagues at the Hôtel-Dieu de Québec Research Centre and the Université Laval completed a ten-year study on the interaction of antioxidants and radiation therapy. This was hailed as the first placebo-controlled, double-blind, randomized trial assessing the effect of supplementation with antioxidant vitamins during radiation therapy. The study concluded that supplements of synthetic beta-carotene (30 mg per day) or alpha tocopherol (400 IU per day) had a harmful effect on cancer patients. In particular, the authors claimed that the cancer recurrence rate was 40 percent higher among patients who had been randomly assigned to the supplementation arm of the trial. They therefore called on patients and physicians to exert caution in using antioxidants until new evidence could be provided by future trials.
Kedar Prasad, PhD, and other proponents of the concurrent use of antioxidants during cancer treatment criticized the Bairati paper. They were disappointed that Bairati and colleagues had used ordinary alpha tocopherol as their choice of vitamin E when Prasad’s previous work had shown that it was not just alpha tocopherol but alpha tocopherol succinate that had the anticancer efficacy. They also felt that natural forms of the vitamin were more effective than synthetic, drug store-type vitamins. But, by and large, the medical world accepted the Bairati trial as definitive proof that antioxidants interfered with radiation therapy. Word spread like wildfire in oncology circles, confirming a long-held belief that antioxidants interfered with standard cancer treatments such as radiation and chemotherapy. The take away message, as stated in a Université Laval press release, was that “Supplements May Speed Up Development of Cancer.” Advocates of complem! entary and alternative medicine (CAM) were confounded by this large and impressive study.
But now the other shoe has dropped.
In December 2007, Dr. Bairati and her Québec colleagues published a major modification of their previous conclusions. Further analysis revealed, they said, that the danger of synthetic antioxidants was limited to one particular sub-population: cigarette smokers – specifically, those who continued to smoke during radiation treatment. The authors analyzed the outcome in 540 patients who had been given radiation for head and neck cancers. During the follow-up period, 119 patients had a recurrence of their disease and 179 died. Smokers were the group with the worst prognosis. However, astonishingly, smoking in the period leading up to or following radiation therapy did not modify the effects of the two supplements. It was only smoking during the course of radiation therapy that led to a statistically significant increase in the risk of a recurrence. It was a large enough increase to skew the statistics for the group as a whole, leading to the erroneous conclus! ion that antioxidants interfered with radiotherapy in the general patient population.
Statistically, increased risk is generally expressed as a “hazard ratio” (abbreviated HR). In this study, current smokers had an HR of 2.41 for recurrence, in other words more than double the chance of a recurrence compared to the rest of the patient population. The HR for death from any cause was a similar 2.26. But the hazard ratio for dying of their initial head and neck cancer was a whopping 3.38 in patients who got radiation, smoked and also received a single synthetic antioxidant.
“These results could best be explained by the hypothesis that the combined exposures reduced the efficacy of radiation therapy,” Bairati and her colleagues now say. “Particular attention should be devoted to prevent patients from both smoking and taking antioxidant supplements during radiation therapy” (Meyer 2007).
According to the National Cancer Institute, 85 percent of head and neck cancers are linked to tobacco use. (Alcohol use further exacerbates this trend.) This has been widely known for years, and so it is shocking that there are still people so hopelessly addicted to tobacco that they not only continue to smoke after they’ve been diagnosed with head and neck cancer but continue to smoke right through their radiation therapy. It was in this subset of particularly unhealthy individuals that antioxidants were associated with an increased risk of disease progression. As Bairati and colleagues suggest, such individuals should definitely not compound their problems by then taking a synthetic antioxidant.
But the more important lesson for patients and practitioners is that antioxidants do NOT generally interfere with the effects of radiation therapy, as was previously suggested. They do NOT increase the risk of a recurrence, of death from head and neck cancer, or of overall mortality in the average patient. In this updated study, the harmful effect of synthetic antioxidants was entirely limited to those relatively few tobacco-addicted patients who continued to smoke during their radiation therapy. Thus, the major premise underpinning oncologists’ condemnation of antioxidants during radiation therapy has crumbled, although few seem to have noticed so far.
References:
Bairati I, Meyer F, Jobin E, et al. Antioxidant vitamins supplementation and mortality: a randomized trial in head and neck cancer patients. Int J Cancer. 2006;119:2221-4.
Bairati I, Meyer F, Gélinas M, et al. Randomized trial of antioxidant vitamins to prevent acute adverse effects of radiation therapy in head and neck cancer patients. J Clin Oncol. 2005;23:5805-5813.
Bairati I, Meyer F, Gélinas M, et al. A randomized trial of antioxidant vitamins to prevent second primary cancers in head and neck cancer patients. J Natl Cancer Inst. 2005;97:481-488.
Meyer F, Bairati I, Fortin A, et al. Interaction between antioxidant vitamin supplementation and cigarette smoking during radiation therapy in relation to long-term effects on recurrence and mortality: A randomized trial among head and neck cancer patients. Int J Cancer. 2007 Dec 4;122(7):1679-168.
February 4th, 2008
New evidence from the Million Women Study finds increased risk for six cancers not previously associated with high BMI.
Increased body-mass index (BMI) raises the risk for adenocarcinoma of the esophagus, endometrial cancer, kidney cancer, and postmenopausal breast cancer in women. But researchers have not conclusively associated high BMI with the risk for other cancers in women. In this large cohort study, investigators in the U.K. recruited 1.2 million women aged 50 to 64 without cancer (except for nonmelanoma skin cancer) between 1996 and 2001. The team assessed the effect of BMI (adjusted for 10 clinical factors) on the incidence of and mortality risk for 17 of the most common types of cancer.
Mean follow-up was 5.4 years. The researchers confirmed the association between increasing BMI and the cancers previously associated with obesity. They also found significant associations between increasing BMI and the risks for leukemia, multiple myeloma, non-Hodgkin lymphoma, pancreatic cancer, ovarian cancer, and — in premenopausal women only — colon cancer. In the 10 cancers that were positively associated with increasing BMI, the risks for cancer mortality were similar to those for cancer incidence. Increasing BMI did not affect risks for malignant melanoma, colorectal cancer, and cancers of the stomach, cervix, bladder, or brain. Increasing BMI decreased risks for lung cancer and squamous-cell carcinoma of the esophagus.
Comment: These sound findings suggest that more cancers are linked to obesity than previously thought. Since the worldwide obesity epidemic shows no signs of abating, we need new approaches to help patients to avoid weight gain, which could prevent many cancers as well as cardiovascular events.
Published in Journal Watch Cardiology January 9, 2008
February 4th, 2008
