__________________
Diagnosed stage 2b in July 2003 (2.3 cm, HER2+, ER-/PR-, 7+ nodes). Treated with mastectomy (with immediate DIEP flap reconstruction), AC + T/Herceptin (off label). Cancer advanced to lung in Jan. 2007 (1 cm nodule). Started Herceptin every 3 weeks. Lung wedge resection April 2007. Cancer recurred in lung April 2008. RFA of lung in August 2008. 2nd annual brain MRI in Oct. 2008 discovered 2.6 cm cystic tumor in left frontal lobe. Craniotomy Oct. 2008 (ER-/PR-/HER2-) followed by targeted radiation (IMRT). Coughing up blood Feb. 2009. Thoractomy July 2009 to cut out fungal ball of common soil fungus (aspergillus) that grew in the RFA cavity (most likely inhaled while gardening). No cancer, only fungus. Removal of tiny melanoma from upper left arm, plus sentinel lymph node biopsy in Feb. 2016. Guardant Health liquid biopsy in Feb. 2016 showed mutations in 4 subtypes of TP53. Repeat of Guardant Health biopsy in Jana. 2021 showed 3 TP53 mutations, BRCA1 mutation and CHEK2 mutation. Invitae genetic testing showed negative for all of these. Living with MBC since 2007. Stopped Herceptin Hylecta (injection) treatment in March 2020. Recent 2021 annual CT of chest, abdomen and pelvis and annual brain MRI showed NED. Praying for NED forever!!
Anemia Drugs' Mortality Risk Supported in Cancer Patients
Increased death rates among cancer patients taking erythropoiesis-stimulating agents were supported in a large meta-analysis.
Among nearly 14,000 patients in 53 studies, those taking the anemia drugs were 17% (95% CI 6% to 30%) more likely to die during the study, and their overall survival chances were reduced by 6% (95% CI 0% to 12%), reported Julia Bohlius, M.D., M.Sc.P.H., of the University of Bern in Switzerland.
The findings, disclosed at the American Society of Hematology meeting, confirmed results reported earlier in individual studies.
The trials included Epogen, Procrit, NeoRecormon and Aranesp. The analysis was notable for relying on full data on each patient, contributed by the trial sponsors and individual investigators, not on outcome data as published.
And in fact, the on-study mortality results were higher than previously published. On-study mortality was defined as death from any cause occurring from randomization to four weeks after the active study's end. Overall survival was measured from randomization to the end of available follow-up.
When the patient pool was limited to about 10,000 patients treated with chemotherapy, the relationship between erythropoiesis-stimulating agents and mortality fell just short of statistical significance.
On-study mortality in the chemotherapy population was increased by 10% for those taking the anemia drugs (95% CI -2% to 24%), and the overall death rate was increased by 4% (95% CI -3% to 11%), the researchers found.
The results changed little when the researchers controlled for known risk factors.
Age, sex, hemoglobin, hematocrit at baseline, type and stage of tumor, and type of study were among the factors researchers took into account.
Patients getting no cancer treatment showed a 33% increase in on-study mortality if they were receiving erythropoiesis agents (95% CI 7% to 67%).
There were even higher increases in patients receiving other forms of cancer treatment (52% for chemoradiation, 52% for radiation alone, and 53% for "other" non-chemotherapies), but these did not reach statistical significance.
Moreover, a test for interaction among all the non-chemotherapy patient groups yielded a P value of 0.42.
Co-author Andreas Engert, M.D., of the University of Cologne in Germany, said the specific reasons for the increased deaths associated with erythropoiesis agents remained unclear, but on the basis of more recent studies, most of the excess deaths are probably from thromboembolic events.
The American Society of Hematology and the American Society of Clinical Oncology would convene a new guideline panel early in 2009 to consider revisions derived from these findings and other developments since the existing version was published.
Since the current guideline was produced, the FDA had required a boxed warning on epoetin and darbopoetin about increased mortality risks for cancer patients.
Source:
Bohlius J, et al., "Recombinant human erythropoiesis stimulating agents in cancer patients: individual patient data meta-analysis on behalf of the EPO IPD Meta-Analysis Collaborative Group" Blood 2008; abstract LBA-6.
I have a normally low rbc - just below the lowest number in the normal range. Naturally on chemo it further plunged. During my second cycle of AC I got the last menstrual period I would have until 7 months after chemo ended. Needless to say, I went out with a bang. I heavily bled for 3 weeks (I had to change my pad every hour or there was a big problem. I had to protect the bed during the night and wear underwear for urine leakage for extra protection). After 3 weeks and a third AC, my rbc was horrible. However, I did my own research at the time and refused Procrit (my onc's drug choice). I wasn't bad enough for a transfusion and by the time the 4th AC rolled around I wasn't bleeding anymore (even though I spotted for 1 week after the heavy bleeding ended). I'm sure glad I found all the earlier studies on this. I also know the wbc boosters aren't much better but I took Leukine (instead of Neulasta) which at least also boost the monocytes, lymphocytes and most importantly, the dendrites so it at least gives you more than just neutrophils as Neulasta does.
The body likes to be in its own perfect balance and affecting one thing can affect so many other things. I suppose if one is seriously ill and in a potentially life threatening situation, one must consider all options but if one is on the edge (as I was), it might be best to use a wait and see as I did and proceed if absolutely necessary.
__________________
Kind regards
Becky
Found lump via BSE
Diagnosed 8/04 at age 45
1.9cm tumor, ER+PR-, Her2 3+(rt side)
2 micromets to sentinel node
Stage 2A
left 3mm DCIS - low grade ER+PR+Her2 neg
lumpectomies 9/7/04
4DD AC followed by 4 DD taxol
Used Leukine instead of Neulasta
35 rads on right side only
4/05 started Tamoxifen
Started Herceptin 4 months after last Taxol due to
trial results and 2005 ASCO meeting & recommendations
Oophorectomy 8/05
Started Arimidex 9/05
Finished Herceptin (16 months) 9/06
Arimidex Only
Prolia every 6 months for osteopenia
NED 18 years!
Said Christopher Robin to Pooh: "You must remember this: You're braver than you believe and stronger than you seem and smarter than you think"
Something else that may be unique about anemia. A study, published in the Canadian Medial Association Journal, suggested that patients with anemia may actually help heal the body rather than harm it, says the new study.
Dr. Ryan Zarychanski, the study's co-author and a scientist at the Ottawa Health Research Institute, felt that doctors have been taught for generations that anemia is bad and they want to help their patients by treating it. However, they failed to consider that anemia may be adaptive and may be exactly the response that the body needs at that time.
Tired blood (anemia) involves a shortage of healthy red blood cells to carry oxygen to the body tissues. In the past, blood transfusions were the only way to treat anemia, until a drug derived from erythropoietin (EPO), a hormone that stimulates bone-marrow cells to produce red-blood cells.
Dr. Zarychanski pointed to evidence that suggests anemia is an evolutionary response to illness occuring in humans. The body has adapted over thousands of years to be anemic at times of stress because it needs to conserve energy. It needs help to fight infection. And when you're anemic, bacteria doesn't grow so well in the blood (an evolutionary response to infection before antibiotics).
In general, healthy adults have red blood cell levels of 14 grams or more per 100 millilitres of blood, while patients are considered to need treatment if their levels are below 10 grams. Patients with mild to moderate anemia (those with levels between 10 and 14 grams) would be better off not being treated.
What Dr. Zarychanski argues is that we should exercise some caution when thinking the best treatment is to automatically transfuse or give drugs to correct anemia.
I wonder if low potassium levels are possibly a coping mechanism due to cancer. Mom has to take supplements to avoid low levels that are said to be a risk to the heart. I don't remember her needing supplementation prior to her recurrence.
Does your Mom take diuretics or other blood pressure medicines Rich? Blood pressure medicines that contain diuretics can lower potassium.
By the way, everyone, sometimes iron supplements can help anemia related to chemo. Iron pills can cause constipation, so I took liquid iron prescribed by a doctor the whole time I took chemo. I never had a procrit shot or a blood transfusion. I never needed any shots for low white blood counts either. I took prescription supplements for that too. I took common liquid iron that can be bought in a pharmacy when I ran out of the prescription liquid iron. No problems, thank goodness !!
I would ask the doctor and see if he or she knows what is causing lower potassium if your mom is not taking diuretics or blood pressure meds.
Try eating foods with potassium like bananas or dried fruit if you are worried about it. Alot of food has potassium. I think you can find a list online somewhere.
Anemia Drugs Increase Mortality in Cancer Patients
A recent review in the Lancet suggests that using erythropoiesis-stimulating agents like Aranesp, Epogen and Procrit may reduce fatigue and combat anemia in cancer patients, while promoting tumor growth, hasten their deaths from cancer and increase their risk of early death from strokes and other cardiovascular events. The study combined data from nearly 14,000 patients in 54 clinical trials.
Although the FDA had slapped a black box warning on the drugs, the study, which was funded by firms that made them, suggested that doctors explain to their patients that treatment of anemia with EPO agents may improve their quality of life by reducing anemia and fatigue, but their survival may be shortened. According to a MedPage Today analysis of the study, the drugs, which stimulate red blood cell production, increased mortality by 17 percent.
Federal laws bar drug companies from paying doctors to prescribe medicines that are given in pill form and purchased by patients from pharmacies. But companies can rebate part of the price that doctors pay for drugs, like the anemia medicines, which they dispense in their offices as part of treatment. The anemia drugs are injected or given intravenously in physicians' offices. Doctors receive the rebates after they buy the drugs from the companies. But they also receive reimbursement from Medicare or private insurers for the drugs, often at a markup over the doctors' purchase price. I am reminded it is still a "chemotherapy concession."
Last year, U.S. Oncology, which funds, develops and helps manage 443 cancer centers in 39 states, complained that patients were harmed by new Medicare coverage policy for anemic cancer patients. The Centers for Medicare & Medicaid Services (CMS) decision limited ESA (erythropoiesis-stimulating agents) treatment to a maximum of eight weeks after a chemotherapy session. It also required physicians to wait until hemoglobin levels dropped below 10 g/dl before starting therapy.
Because CMS did not receive any documented cases of negative outcomes from the oncology community, it stuck to its decision. The FDA backed CMS' National Coverage Decision (NCD), which limited use of the drugs because they have been shown to spur tumor growth. The FDA believed the approved labeling and CMS' NCD were generally consistent in their recommendations regarding the use of pharmaceutical EPO in patients with cancer undergoing chemotherapy.
However, major insurance companies had not embraced the CMS protocol. It was a "shot over the bow" by the oncology community of government stepping directly into patients lives and saying that they know what is a better course of treatment than doctors. During the ensuing year, we found out that drugs, given by injection, had been heavily advertised, and there was gathering evidence that they had been overused, in part because oncologists could make money by using more of the drug.
Resulting studies had suggested the drugs may make the cancer worse. Much of that evidence came from studies in which patients were treated more aggressively than the drugs' labels recommended. The FDA found mounting evidence of documented effects on survival, tumor progression and thrombotic events which required reassessment of the net benefit of this class of drugs.
Gee, could it be that increased numbers of red cells deliver more oxygen to the tumor cells and thereby their activity across the board, including with respect to invasion, proliferation and metastasis? On one hand we're developing drugs to halt and reverse angiogenesis while on the other hand we're helping the tumor to obtain more oxygen with existing vasculature.
Having said all of this, physicians, scientists and the public occasionally apply their own judgement and determine when the existing evidence is sufficient to support a personal decision to adopt - as opposed to impose upon others - certain drug treatments. No wonder the National Coalition for Cancer Survivorship emphasized the need for drastic changes in how physicians are reimbursed for care. Reward doctors for whole patient care - not just treatments.
"The connection here is iron," explained Sasaki.
Artemisinin is good at killing malaria parasites because it reacts and becomes highly toxic in the presence of iron, he said. Malaria parasites cause illness in humans by consuming red blood cells, which contain iron in the hemoglobin protein that carries oxygen in the blood. Similarly, cancer cells use lots of iron as they proliferate in tumors.
.........
In the report published this month, the UW trio describe how they have created their own kind of artemisinin compound to enhance the herb's cancer-killing abilities. Basically, the scientists manipulated the herb's protein surface and boosted it with iron. When the cancer cells consume the compound, it releases toxic chemicals that kill the cells.
"The compound is like a little bomb-carrying monkey riding on the back of a Trojan horse," Lai said in a statement accompanying the report. Lai, who is perhaps best known publicly for his controversial studies linking cancer and cell phone use, is not afraid to mix humor with science, let alone metaphors.
Most chemotherapy drugs today have serious side effects, Sasaki said, because they generally kill one healthy cell for every 10 cancer cells. The UW's artemisinin compound used in cell cultures and in rats with breast cancer showed much better targeting and less collateral damage -- killing about 12,000 cancer cells for every healthy cell killed. Even regular artemisinin, without the UW alteration, only kills one good cell for every 100 cancer cells, he said. "Normal cells don't use iron very often," Sasaki said. "When we deliver this artemisinin-iron package to cancer cells, we have much higher selectivity and much less toxic side effects."
And.. Anemia may be helpful Anemia Of Chronic Disease: An Adaptive Response?
ScienceDaily (Aug. 12, 2008) — The anemia of chronic disease may be a beneficial, adaptive response to the underlying disease, rather than a negative effect of the illness, postulates an analysis article in CMAJ.
The authors argue that anemia may be beneficial to patients with inflammatory disease, and advocate restraint in treating mild to moderate forms of anemia.
"The general assumption is that anemia is a disorder and that patients would be better off without it," state the authors.
However, they suggest that anemia of chronic disease has the characteristics of an adaptive physiologic response, and their review of the literature shows that mortality appears to increase when treatment, given to raise hemoglobin levels, overrides mild to moderate anemia of chronic disease.
They call for better characterization of the cause of individual patients' anemia in future trials of anemia treatment, and careful monitoring of adverse outcomes, including mortality, if patients with anemia of chronic disease are included in such trials. Journal reference:
Ryan Zarychanski, MD and Donald S. Houston, MD PhD. Anemia of chronic disease: A harmful disorder or an adaptive, beneficial response?Canadian Medical Association Journal, 2008; 179 (4): 333 DOI: 10.1503/cmaj.071131
ErbB2 (HER2, neu) is a receptor tyrosine kinase overexpressed in about 25% of invasive breast carcinomas. Neutrophil gelatinase-associated lipocalin (NGAL) is a secreted glycoprotein expressed in a variety of cancers, including breast carcinomas. NGAL can inhibit erythroid cell production, leading to anemia. Anemia usually occurs in cancer patients and negatively affects quality of life. However, current treatment for cancer-related anemia has potential complications. ErbB2, NGAL, and anemia have all been associated with increased metastasis and poor prognosis in breast cancer patients, although the relationship between ErbB2 and NGAL expression is not clear. Here, using breast cancer cell lines in vitro and transgenic mice carrying the activated c-neu oncogene driven by a mouse mammary tumor virus (MMTV-neu) in vivo, we show that ErbB2 overexpression leads to NGAL upregulation, which is dependent on nuclear factor-kappaB (NF-kappaB) activity. MMTV-neu transgenic mice developed anemia after tumor onset, and anemia progression could be partially arrested by a NF-kappaB inhibitor and ErbB2-targeted therapy. Taken together, upregulation of NGAL by ErbB2 through NF-kappaB activation is involved in cancer-related anemia, and the ErbB2, NF-kappaB, and NGAL pathways may serve as potential therapeutic targets for cancer-related anemia.
PMID: 19951994 [PubMed - indexed for MEDLINE]PMCID: PMC2794902 [Available on 2010/12/15]
A new review of data confirms that erythropoietin - a drug to treat anemia in many cancer patients - might be harmful. The review found that patients with head and neck cancers who received erythropoietin in combination with radiation had poorer outcomes than those who received radiation treatment alone.
The review appears in the latest issue of The Cochrane Library, a publication of The Cochrane Collaboration, an international organization that evaluates medical research. Systematic reviews draw evidence-based conclusions about medical practice after considering both the content and quality of existing medical trials on a topic.
Severe anemia in cancer patients can lead to decreased oxygen supply to tumor cells. A lower level of oxygen in tumor cells is associated with more rapid tumor progression and a poorer response to therapy. Many use erythropoietin, or EPO, a hormone that controls red blood cell production, to correct anemia.
"It has therefore been thought logical that using erythropoietin to correct anemia before or during chemotherapy, radiotherapy or both would improve prognosis," the review authors write.
Dr. Philippe Lambin and colleagues at the MAASTRO (Maastricht Radiation Oncology) Clinic in the Netherlands conducted the review.
The investigators analyzed data from five published clinical trials that looked at whether combined radiation and EPO was better than standard radiation therapy alone in the treatment of head and neck cancers. Nearly 1,400 patients were included in the analysis. The researchers compared overall survival, the length of time during and after treatment in which the cancer did not progress, local tumor control and toxicity in the two different treatment groups.
Researchers found that patients who received EPO had significantly worse overall survival compared to patients who did not receive the drug. In addition, patients who took EPO had significantly shorter times before their cancers worsened.
Data included in the review suggest that decreased survival rates in cancer patients who took EPO were not due to some toxic effect of the drug itself, such as an increase in deaths due to blood clots. Instead, researchers have hypothesized that the drug might actually cause some types of tumors to grow.
Barbara Burtness, M.D., chief of the Head and Neck Medical Oncology division at the Fox Chase Cancer Center in Philadelphia, commented on the use of erythropoietin in head and neck cancer.
"The primary use of erythropoietin in cancer patients is to raise hemoglobin when patients become anemic, either because of the cancer or because of a side effect of the cancer treatments," she said. "It's been a part of practice for a long time."
Burtness said that there has been a specific reason for studying EPO in head and neck cancers. "When radiation treatments are given for bulky cancers in the head and neck area, it's thought that cancer cells that don't have a high oxygen content are less susceptible to being killed by radiation. The hypothesis has been that if you could correct a patient's anemia, there would be more red blood cells traveling to the area of cancer. This would lead to correction of the low oxygen content in the tumors - and the patient would be more likely to respond to the radiation treatment," she said.
"But what we've been hearing for some time is that erythropoietin is actually making cancer outcomes worse," she said.
She said the United States has tightened guidelines EPO use in response to data from recent studies. "Giving erythropoietin can have a negative impact on survival. We certainly are not using it here [at Fox Chase Cancer Center]. Among our patients who've received radiation elsewhere, its use does not appear to be common."
Manufacturers promoted EPO to improve anemia, and to help anemic patients to feel better overall. However, the U.S. Food and Drug Administration has issued several public health advisories underscoring the possible risks of using EPO in cancer, including faster tumor growth and early death. The FDA warnings also say that EPO does not improve symptoms associated with anemia, such as fatigue. Nor does EPO improve a patient's quality of life or sense of well-being, the advisories say.
The authors of the review conclude that patients with head and neck cancer should not receive EPO as an addition to radiation therapy.
Source: Health Behavior News Service and GoozNews on Health
Drug therapy for the management of cancer related fatigue
Aspirin-associated iron loss as an anticancer mechanism.
Mascitelli L, Pezzetta F, Sullivan JL.
Medical Service, Comando Brigata Alpina "Julia", Udine, Italy.
A consensus view has emerged favoring an anticancer effect of long-term aspirin use. Aspirin-induced loss of stored iron from chronic gastrointestinal bleeding is proposed as a mechanism underlying this beneficial effect. In iron depletion, less iron may be available for carcinogenesis through free-radical mediated mechanisms and for promotion of tumor growth. Low-dose aspirin increases gastrointestinal losses of transfused radiolabeled autologous red cells. Observational studies report lower serum ferritin values with regular aspirin use. A protective effect of induced iron reduction against cancer mortality has been confirmed in a recent trial (FeAST) with subjects randomized to iron reduction or observation. Serum ferritin reductions in the FeAST trial were within conventionally normal reference ranges and were quantitatively similar to ferritin reductions in observational studies in regular aspirin users. Delayed anticancer effects of aspirin are compatible with the proposed mechanism, as continual microbleeding has a gradual cumulative effect on stored iron.
PMID: 19692186 [PubMed - as supplied by publisher
Clin Transl Oncol. 2009 Nov;11(11):727-36. Spanish Society of Medical Oncology consensus on the use of erythropoietic stimulating agents in anaemic cancer patients.
Nearly two years after a Food and Drug Administration advisory committee called for restrictions on the use of red blood cell-stimulating drugs in cancer patients (erythropoiesis-stimulating agents or ESAs), the agency unveiled a stringent risk management plan that should further lower use of the drugs, which are already in freefall in cancer patients. The plan, which affects Amgen's Aranesp and Epogen and Johnson & Johnson's Procrit (manufactured by Amgen and identical to Epogen), requires the companies:
Register oncologists who prescribe the drugs;
Educate them about their risks, which include tumor progression and earlier death; and
Fully inform patients about the risks with an updated medication information guide, both at the time they are initially treated and every time treatment is given; and
Obtain signatures from patients that they've been apprised of the risks.
The updated medication guide will contain information for chronic and end-stage renal disease patients, who also get ESAs for anemia. But renal physicians will not be facing the same registration and education requirements.
The company was given a year to come into full compliance. Officials at a press briefing yesterday were uncertain what would happen to oncologists or the companies if they prescribe or use the drugs without giving the proper warnings.
The program is called, appropriately enough, APPRISE. And while it's tough, it's not unprecedented. The FDA adopted a similar registration program for some opioids.
When pressed by a reporter on why it took so long to come up with the program, Richard Pazdur, head of the oncology office at the Center for Drug Evaluation and Research at FDA, said "this took many many months of discussion. It's a delicate balance. We don't want to interfere in a draconian fashion with the practice of medicine."
Pazdur distinguished between patients undergoing therapy where there is a chance of cure, and those receiving palliative care for incurable cancers. In the latter case, patients may opt for the greater energy that comes from alleviating cancer- and chemo-related anemia, even if it results in a shorter end game.
"The risks-benefit balance is a delicate one," Pazdur said. The goal of the program wasn't to restrict use of the drugs, but "to help patients make the best choice given their individual situation."
The failure to simultaneously force the companies to reeducate the renal physician community was disappointing. There's mounting evidence that high doses of ESAs in renal disease patients is associated with increased risk of heart attacks, strokes and earlier mortality. Many of these patients are poor and unaware of the quality of care they receive at dialysis centers. They, just as much as cancer patients, need to be informed about the risks posed by overuse of ESAs.
Neoplasia. 2007 Dec;9(12):1122-9.
Effects of recombinant erythropoietin on breast cancer-initiating cells.
Phillips TM, Kim K, Vlashi E, McBride WH, Pajonk F.
Department of Radiation Oncology, David Geffen School of Medicine, University of California, Los Angeles, 10833 LeConte Ave, Los Angeles, CA 90095-1714, USA.
BACKGROUND: Cancer anemia causes fatigue and correlates with poor treatment outcome. Erythropoietin has been introduced in an attempt to correct these defects. However, five recent clinical trials reported a negative impact of erythropoietin on survival and/or tumor control, indicating that experimental evaluation of a possible direct effect of erythropoietin on cancer cells is required. Cancer recurrence is thought to rely on the proliferation of cancer initiating cells (CICs). In breast cancer, CICs can be identified by phenotypic markers and their fate is controlled by the Notch pathway. METHODS: In this study, we investigated the effect of erythropoietin on CICs in breast cancer cell lines. Levels of erythropoietin receptor (EpoR), CD24, CD44, Jagged-1 expression, and activation of Notch-1 were assessed by flow cytometry. Self-renewing capacity of CICs was investigated in sphere formation assays. RESULTS: EpoR expression was found on the surface of CICs. Recombinant human Epo (rhEpo) increased the numbers of CICs and self-renewing capacity in a Notch-dependent fashion by induction of Jagged-1. Inhibitors of the Notch pathway and PI3-kinase blocked both effects. CONCLUSIONS: Erythropoietin functionally affects CICs directly. Our observation may explain the negative impact of recombinant Epo on local control and survival of cancer patients with EpoR-positive tumors.
PMID: 18084619 [PubMed - indexed for MEDLINE]
Clin Cancer Res. 2009 Sep 1;15(17):5552-9. Epub 2009 Aug 25.
Erythropoietin receptor expression and correlation to tamoxifen response and prognosis in breast cancer.
Annu Rev Med. 2009;60:181-92.
Erythropoietin in cancer patients.
Glaspy JA.
Division of Hematology-Oncology, Department of Medicine, School of Medicine, University of California, Los Angeles, California 90095, USA. jglaspy@mednet.ucla.edu
Therapy with erythropoiesis-stimulating agents (ESAs) is associated with well-documented benefits to anemic cancer patients undergoing chemotherapy, most importantly a reduction in the likelihood of needing red cell transfusions. One challenge in supportive cancer care is a relative resistance to ESAs, requiring high doses with a significant rate of nonresponse. Recent advances in our understanding of iron metabolism in patients with chronic illness and the results of clinical trials indicate that parenteral iron improves ESA response in this setting. Another issue is the safety of ESA treatment in cancer patients. There is an increased risk of venous thrombosis that must be considered in clinical decision making. There are also recent data raising concerns that ESAs may enhance tumor progression or decrease patient survival. Although the preponderance of the data suggests that ESAs do not alter survival when used to treat chemotherapy-induced anemia, large well-controlled trials addressing this issue are needed.
PMID: 18980468 [PubMed - indexed for MEDLINE]
Am J Health Syst Pharm. 2009 Jul 1;66(13):1180-5.
Use of erythropoietin-stimulating agents in breast cancer patients: a risk review.
Crouch Z, DeSantis ER.
Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.
PURPOSE: The treatment of cancer-induced anemia with erythropoietin-stimulating agents (ESAs) is reviewed. SUMMARY: Before the introduction of ESAs, the only treatment option for cancer-related anemia was red blood cell (RBC) transfusion. The use of ESAs in multiple disease states has been well established and is now considered first-line treatment for many forms of anemia. Chang et al. evaluated the effect of epoetin alfa (40,000 units administered subcutaneously every week) and standard-of-care therapy on quality of life (QOL), transfusion requirements, and hemoglobin levels in 354 patients with breast cancer who had a baseline hemoglobin concentration of <15 g/dL. The authors concluded that early initiation of treatment with epoetin alfa in patients with breast cancer is effective in maintaining hemoglobin levels, reducing transfusions, and improving QOL. Leyland-Jones et al. conducted a study evaluating the effects of early intervention with epoetin alfa (40,000 units administered subcutaneously every week) on survival and QOL of mainly nonanemic patients with metastatic breast cancer. In contrast to Chang et al., this study was discontinued because of lower overall survival rates within the epoetin alfa group. In 2008, the Food and Drug Administration issued a black-box warning for both epoetin alfa and darbepoetin alfa. The warning acknowledges that ESAs have shortened overall survival and time to disease progression in patients with advanced breast cancer who are given these agents to achieve a target hemoglobin concentration of > or =12 g/dL. CONCLUSION: When used in patients with cancer-induced anemia, ESAs should only be given at the lowest dose possible to prevent RBC transfusions. During treatment, hemoglobin levels should be monitored closely and ESA doses need to be adjusted accordingly.
PMID: 19535656 [PubMed - indexed for MEDLINE]
Br J Cancer. 2009 Dec 15;101(12):1961-71. Epub 2009 Sep 29.
Epoetin-beta treatment in patients with cancer chemotherapy-induced anaemia: the impact of initial haemoglobin and target haemoglobin levels on survival, tumour progression and thromboembolic events.
BACKGROUND: Epoetin-beta is used to treat patients with cancer undergoing chemotherapy to alleviate the symptoms of anaemia, reduce the risk of blood transfusions and improve quality of life (QoL). METHODS: This meta-analysis of all 12 randomised, controlled studies of epoetin-beta evaluated the impact of therapy at different Hb-initiation levels and to different target Hb levels on overall survival, tumour progression and thromboembolic events (TEE). An analysis of risk factors pre-disposing patients to TEEs under epoetin-beta therapy was also performed. A total of 2297 patients are included in the analysis. RESULTS: Analyses based on various Hb-initiation levels indicate no detrimental impact on survival (HR 0.99; 95% CI 0.70, 1.40) and a favourable impact on disease progression (HR 0.73; 95% CI 0.57, 0.94) when epoetin-beta was used within its licensed indication (Hb initiation < or = 10 g dl(-1)) or the EORTC recommended level of 11 g dl(-1). An increased risk of TEEs is seen for all Hb-initiation level strata and a detrimental impact on survival is seen when initiating epoetin-beta therapy at Hb levels >11 g dl(-1). We observe no association between high target Hb levels (> or = 13 g dl(-1)) and an increased risk of mortality, disease progression or TEEs with epoetin-beta compared with control. CONCLUSION: The results of this analysis indicate that epoetin-beta therapy has no detrimental impact on survival or tumour progression when initiated at Hb levels up to 11 g dl(-1). Furthermore, there is no evidence to suggest that high Hb values achieved during epoetin-beta therapy are associated with an increased mortality, disease progression or TEE rate.
PMID: 19997109 [PubMed - indexed for MEDLINE]
Acta Haematol. 2011;125(1-2):55-67. Epub 2010 Dec 8. Twist and shout: one decade of meta-analyses of erythropoiesis-stimulating agents in cancer patients.
Bohlius J, Tonia T, Schwarzer G.
Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.
The findings of several meta-analyses on ESAs in cancer patients demonstrate that ESAs reduce the risk for RBCT and increase the risk for TVEs and mortality. There is an ongoing debate whether or not ESAs increase mortality in cancer patients receiving chemotherapy as well. However, the currently available data are insufficient to exclude an increased risk for death in cancer patients undergoing chemotherapy and receiving ESAs. In clinical practice, the increased risks of death and TVEs should be balanced against the benefits of treatment with ESAs, taking into account each patient’s clinical circumstances and preferences.
Aranesp (darbepoetin alfa) is an injectable drug that stimulates the production of red blood cells in the body. Often, patients who undergo dialysis or chemotherapy develop severe anemia that leaves them weak. Aranesp helps them recover from the tough treatments faster and reduces the need for transfusions. Amgen's drug Epogen and Johnson & Johnson's (JNJ) Procrit belong to the same family of drugs, called erythropoiesis-stimulating agents (ESAs).
Concerns over these drugs have been mounting in recent years after a series of studies found that high doses can lead to increased risks of heart attack, stroke, heart failure and tumor growth in some patients. As a result, in 2007, the Food and Drug Administration issued a black-box warning -- the strongest warning possible about potential side affects -- for Aranesp, Epogen and Procrit. Aranesp sales have declined in recent years as a result.
Less than two weeks ago, a new study published in The New England Journal of Medicineraised fresh safety concerns about the widely used anemia medicine. The study found that Aranesp nearly doubled the risk of stroke in people with diabetes and chronic kidney problems who are not yet sick enough to need dialysis.
Checking drugs out....
Death Risk Found from Anemia Drugs
Blood components and possible "invisible" effects
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