Omega-3 Meds Not Effective After MI, EMA Panel Concludes

The European Medicine Agency’s (EMA’s) Committee for Medicinal Products for Human Use (CHMP) has concluded that omega-3 fatty acid medicines are not effective for secondary prevention after myocardial infarction (MI).

Omega-3 fatty acid medicines at a dose of 1 g per day have been authorized in several European Union countries since 2000 for preventing heart disease or stroke after MI and for lowering high triglycerides.

When they were authorized, the available data showed “some benefits in reducing serious problems with the heart and blood vessels, although the benefits were considered modest,” the EMA said in a news release. “Further data that have become available since then have not confirmed the beneficial effects of these medicines for this use.”

The CHMP’s conclusion, released at their December meeting, means that these medicines will no longer be authorized for such use.

Their review included results of the open-label GISSI Prevenzione study from 1999, which supported the initial authorization of these products, as well as retrospective cohort studies, more recent randomized controlled trials, and results of meta-analyses.

“The review concluded that, while a small relative risk reduction was seen in the original open label GISSI Prevenzione study, such beneficial effects were not confirmed in more recent randomized controlled trials,” the EMA said. The review found no new safety concerns.

The Committee’s decision does not affect the authorization of omega-3 fatty acid medicines for the treatment of hypertriglyceridemia.

The CHMP opinion will now be forwarded to the European Commission, which will issue a final legally binding decision applicable in all EU member states.

Support for the CHMP decision comes from results of the large VITAL trial, which found little benefit from omega-3 supplements (or vitamin D supplementation) for the prevention of cardiovascular disease, as reported by Medscape Medical News.

In the ASCEND trial, a 1 g dose of omega-3 fatty acids had no effect on serious vascular events (or cancer or mortality) when used for primary prevention in patients with diabetes.

However, in the REDUCE-IT trial, a high-dose purified form of the omega-3 oil, eicosapentaenoic acid (EPA), in patients with elevated triglycerides who had cardiovascular disease or diabetes and one additional risk factor did show significant benefit, with a 25% relative risk reduction in major adverse cardiovascular events.

Genomic Studies Allow Better Classification of Leukemias, Endometrial Tumors.

Two studies, one of leukemia and the other of endometrial tumors, show the usefulness of genomics studies in finding unsuspected classifications, possibly useful for treating these cancers.

One study, published in the New England Journal of Medicine, examined 200 cases of acute myeloid leukemia. Genomic studies allowed the researchers to discern nine distinct categories, revealing “many potentially important biologic relationships.” For instance, certain mutations were associated with distinct patterns of RNA activity. The authors point out that the significance of such findings “is not yet clear.”

Another study, in Nature, of some 375 endometrial cancers found four distinct classes of the disease, as opposed to the two commonly used to stage treatment. In Journal Watch Oncology and Hematology, Virginia Kaklamani observes that breast cancer was the first to use molecular subtypes to guide treatment. The Nature study, she writes, is “a huge step toward applying this technique in other malignancies.”


Autologous and Allogeneic Stem-Cell Transplantation for Transformed Follicular Lymphoma: A Report of the Canadian Blood and Marrow Transplant Group.


Purpose To determine whether autologous (auto) or allogeneic (allo) stem-cell transplantation (SCT) improves outcome in patients with transformed follicular lymphoma compared with rituximab-containing chemotherapy alone.

Patients and Methods This was a multicenter cohort study of patients with follicular lymphoma and subsequent biopsy-proven aggressive histology transformation. Patient, treatment, and outcome data were collected from each transplantation center and combined for analysis. A separate control group was composed of patients with transformation treated with rituximab-containing chemotherapy but not SCT. The primary end point was overall survival (OS) after transformation.

Results One hundred seventy-two patients were identified: 22 (13%) treated with alloSCT, 97 (56%) with autoSCT, and 53 (31%) with rituximab-containing chemotherapy. Five-year OS after transformation was 46% for patients treated with alloSCT, 65% with autoSCT, and 61% with rituximab-containing chemotherapy (P = .24). Five-year progression-free survival (PFS) after transformation was 46% for those treated with alloSCT, 55% with autoSCT, and 40% with rituximab-containing chemotherapy (P = .12). In multivariate analysis, patients treated with autoSCT had improved OS compared with those who received rituximab-containing chemotherapy (hazard ratio [HR], 0.13; 95% CI, 0.05 to 0.34; P < .001). On the other hand, there was no OS difference between those treated with alloSCT and rituximab-containing chemotherapy (HR, 0.44; 95% CI, 0.16 to 1.24; P = .12). OS and PFS after SCT were similar between those treated with autoSCT and alloSCT. Five-year transplantation-related mortality was 23% for those treated with alloSCT and 5% for autoSCT.

Conclusion Patients undergoing autoSCT had better outcomes than those treated with rituximab-containing chemotherapy alone. AlloSCT did not improve outcome compared with rituximab-containing chemotherapy and was associated with clinically significant toxicity.

Source: JCO



Breast Irradiation and Increased Risk for Ischemic Heart Disease: New Data Emerge.

A case-control study in the New England Journal of Medicine provides new information on the link between breast irradiation and increased risk for ischemic heart disease.

Using national registries, researchers in Sweden and Denmark studied nearly 2200 women who underwent radiotherapy for breast cancer between 1958 and 2001; roughly 1000 who subsequently had a major coronary event were matched with 1200 controls.

The rate of coronary events increased with the mean estimated dose of radiation to the heart. The risk increase was observed within 5 years after treatment and lasted for at least 20 years. The absolute risk for coronary events was particularly high for women who had preexisting cardiac risk factors.

In Journal Watch Oncology and Hematology, William Gradishar concludes: “Efforts to provide women with the option of breast conservation should not be abandoned, but for select women with very significant cardiac risk factors … a mastectomy might be a better option.”

Source: NEJM 


Transcatheter Arterial Catheter Embolization for Hepatocellular Cancer.


TACE, plus radiofrequency ablation, was superior to RFA alone in patients with liver-confined disease.

For patients with liver-limited, nonresectable hepatocellular cancer (HCC), treatment options include alcohol injection, radiofrequency ablation (RFA), and transcatheter arterial catheter embolization (TACE), with or without chemotherapy. However, the optimal therapy has not been clearly defined.

Now, Chinese investigators have conducted a single-institution, randomized trial to compare RFA, with or without TACE, in HCC patients with a solitary liver lesion ≤7 cm in size (or ≤3 lesions, each ≤3 cm in size), Child’s Pugh A or B liver disease, and no evidence of hepatic or portal venous invasion. All patients received RFA (up to 3 applications per session; an additional session was permitted if imaging indicated persistent viable tumor). For patients who received RFA plus TACE, hepatic artery infusion chemotherapy with carboplatin (300 mg) was followed by embolization with lipiodol (5 mL), epirubicin (50 mg), and mitomycin (8 mg) followed within 2 weeks by RFA. Of the nearly 2300 patients screened, 189 were treated. Most were male (89%) and positive for hepatitis B surface antigen (89%), and most had Child’s Pugh A liver disease (95%) and a solitary liver lesion (68%).

Recurrence rates trended lower with TACE plus RFA compared with RFA alone (35.1% and 54.7%, respectively). Overall survival (OS; the primary endpoint) was significantly better with TACE plus RFA (hazard ratio, 0.525; P=0.002; 4-year OS rates, 61.8% vs. 45.0%). Recurrence-free survival (RFS) was also significantly better with TACE plus RFA (HR 0.575; P=0.009; 4-year RFS rates, 54.8% vs. 38.9%). Complication rates were similar in the two therapy arms.

Comment: These results support the combination of RFA and chemoembolization for selected patients with liver-confined HCC. Issues remaining to be resolved include the role of chemotherapy added to embolization compared with embolization alone. The large degree of patient exclusion after screening, the relatively small number of patients treated, and the conduction of the trial at a single institution call into question the extent to which the findings can be generalized.

Source: Journal Watch Oncology and Hematology

PET and Prognosis in Follicular Lymphoma.

A negative posttreatment PET scan was associated with improved survival in patients with advanced-stage disease.

Complete remission with a negative positron emission tomography (PET) scan after front-line induction chemotherapy is associated with improved outcomes in Hodgkin lymphoma and diffuse large B-cell lymphoma. To assess the prognostic value of PET in follicular lymphoma (FL), European investigators conducted a prospective, multicenter trial involving 117 patients with advanced-stage, high–tumor burden FL who were treated with six cycles of R-CHOP (rituximab plus cyclophosphamide, vincristine, doxorubicin, and prednisone) followed by two additional doses of rituximab. PET scans were performed at baseline, after cycle four (PETC4), and at completion of therapy (PETC8). Independent central review of PET response was performed by three nuclear medicine radiologists and classified by established criteria (Deauville 5-point scale). No treatment modifications were made based on PET findings.

Results were as follows:

  • Of 106 patients who underwent PETC8 imaging, 83 (78%) had negative results.
  • Of 78 patients with negative PETC4 results, 6 (8%) reverted to a positive posttreatment scan.
  • Of 26 patients with positive PETC4 results, 17 (65%) remained positive on PETC8.
  • When comparing PET response to standard computed tomography–based assessment, 53 of 54 patients (98%) with complete remissions were PET-negative, whereas 10 of 20 patients (50%) with complete remissions unconfirmed (CRu) and 9 of 26 patients (35%) with partial remission (PR) remained PET-positive.
  • Patients with negative posttreatment PET had improved 2-year overall survival versus those with a positive scan (100% vs. 88%; P=0.01).
  • Progression-free survival was improved for those with negative versus positive PETC4 or PETC8.

Comment: This is the first prospective study to demonstrate a prognostic benefit for negative posttreatment PET in FL. The predictive value was independent of both low-risk and high-risk FLIPI (Follicular Lymphoma International Prognostic Index) scores. The authors recommend that only posttreatment PET rather than interim PET be used and that scan use be reserved for CRu and PR patients. Confirmation of these results in additional prospective trials will be important, as will careful application of standardized PET response criteria and PET response–based treatment algorithms.

Source: Journal Watch Oncology and Hematology


FDA Approves New Drug to Treat Chronic Myelogenous Leukemia.

The Food and Drug Administration has approved bosutinib (Bosulif) to treat chronic myelogenous leukemia (CML), a blood and bone marrow disease that usually affects older adults. Bosutinib is intended for patients with chronic, accelerated, or blast phase Philadelphia chromosome-positive CML who are resistant to or who cannot tolerate other therapies, including imatinib (Gleevec).

Most people with CML have a chromosomal aberration called the Philadelphia chromosome, which causes the bone marrow to make an abnormal tyrosine kinase enzyme called Bcr-Abl. This enzyme promotes the proliferation of abnormal and unhealthy infection-fighting white blood cells called granulocytes. Bosutinib is a tyrosine kinase inhibitor (TKI) that works by blocking Bcr-Abl signaling.

Bosutinib’s safety and effectiveness were evaluated in a clinical trial involving 546 adults with chronic, accelerated, or blast phase CML. All of the patients had been previously treated with at least one TKI, either imatinib or imatinib followed by dasatinib (Sprycel) and/or nilotinib (Tasigna).

Among patients with chronic phase CML, 34 percent of patients who had been treated previously with imatinib and 27 percent of those who received more than one prior TKI achieved a major cytogenetic response within 24 weeks.

Among patients with accelerated phase CML who had received at least one prior TKI, 30 percent had their blood counts return to the normal range (a complete hematologic response) by week 48, and 55 percent achieved a complete hematologic response, no evidence of leukemia, or return to chronic phase (an overall hematologic response) by week 48. Among patients with blast phase CML who had received at least one prior TKI, 15 percent had a complete hematologic response and 28 percent an overall hematologic response by week 48.

The most common side effects observed in those receiving bosutinib were diarrhea, nausea, a low level of platelets in the blood, vomiting, abdominal pain, rash, anemia, fever, and fatigue.

Source: NCI


Stem Cell Transplant Experts Discuss the Procedure and How to Become a Stem Cell Donor.

This morning, Good Morning America co-host Robin Roberts announced that she will undergo a bone marrow transplant at Memorial Sloan-Kettering Cancer Center. Learn about the treatment and recovery process from Memorial Sloan-Kettering experts.

Over the course of three decades, Memorial Sloan-Kettering physicians have performed more than 4,000 bone marrow transplants – nearly 400 annually in recent years. This procedure, also known as a stem cell transplant, is used to replenish bone marrow and hematopoietic stem cells that have been destroyed due to a variety of reasons, such as certain types of cancer, cancer treatments, blood diseases, or immune disorders. Hematopoietic, or blood-forming, stem cells are produced in the bone marrow.

Our investigators have also been at the forefront of research in stem cell transplantation since 1973, when our doctors performed the world’s first successful transplant between a patient and an unrelated donor. Many of the transplant approaches and supportive care regimens widely used today were pioneered at Memorial Sloan-Kettering.

In a recent interview, experts on our Adult Bone Marrow Transplantation Service talked about the procedure, the recovery process, and how to become a bone marrow or stem cell donor.

What does a stem cell transplant involve?

There are two main types of transplants. In an autologous transplant, a patient’s own stem cells are collected and then transplanted back. In an allogeneic transplant, the stem cells are obtained from another person or from donated umbilical cord blood and then given to the patient.

Before either type of transplant, the patient receives high doses of chemotherapy or a combination of chemotherapy and radiation therapy to kill any cancerous cells and hematopoietic stem cells in the bone marrow. Healthy blood stem cells are then transplanted into the bloodstream through an intravenous catheter, in a process similar to a blood transfusion.

The stem cells migrate to the bone marrow, where after several weeks they usually begin to develop into new infection-fighting white blood cells, oxygen-rich red blood cells, and blood-clot-forming platelets.

How do doctors decide that a person should receive a transplant?

We carefully select patients for this procedure because transplantation can be extremely challenging for a patient and his or her family. This is both because of the toxicity of the high-dose regimens before the transplant and because the patient’s immune system must be suppressed for an extended period of time after the procedure to prevent a rejection of the transplanted cells.

Despite the risks, outcomes have dramatically improved over the past decades, and stem cell transplants can often cure a person’s disease. In fact, a recent study conducted by the National Marrow Donor Program found that Memorial Sloan-Kettering significantly exceeded its predicted one-year survival rate for patients undergoing an allogeneic transplant.

What is the recovery process like for a patient?

Most patients remain in the hospital for several weeks to receive medical support. To protect against infection, everyone who enters the patient’s room is required to wear gloves, masks, and sometimes disposable gowns, and to wash their hands with antiseptic soap. Patients can’t have any fresh fruit, flowers, or plants in their rooms, as these can carry disease-causing molds and bacteria.

The first year after the transplant is critically important because it’s the period when complications – such as infection or rejection – are most likely to happen. Patients are typically able to get back to their regular activities after a year, with a lower risk of developing an infection.

How do you identify donors for patients who need an allogeneic transplant?

Finding an appropriate donor is critical to the success of an allogeneic transplant. Because the immune system can identify and destroy any cells perceived as foreign, a donor’s tissue type should match the patient’s as closely as possible. The process of tissue typing is based on analyzing proteins called human leukocyte antigens (HLA), which are found on the surface of white blood cells and tissues.

We work closely with our patients to find a bone marrow match. Often, the ideal donor is a sibling who has inherited the same HLA. The majority of patients do not have a brother or sister who is a match, so we can look for other family members who may be a partial match. But because family size is getting smaller in North America, it is becoming more challenging to find appropriate family member donors.

We often look to volunteer donor registries, such as the National Marrow Donor Program, and in some cases we consider using umbilical cord blood stored in public banks, such as through National Cord Blood Program. It can also be difficult to find stem cells from people of mixed ethnic or minority backgrounds through these registries, so we encourage more people to consider becoming a donor.

How can I register to become a bone marrow or stem cell donor?

You can join the Be The Match Registry or DKMS Americas. Everyone who is medically able should consider becoming part of a marrow registry. Learn more about who can donate, donor requirements, and medical guidelines from the National Marrow Donor Program.

Source: MSKCC.

Therapeutic vs. Prophylactic Platelet Transfusions

Prophylactic platelet transfusions might not be needed for thrombocytopenic patients undergoing stem-cell transplantation, but are indicated for those receiving chemotherapy for acute myeloid leukemia.

Current practice is to give platelet transfusions to patients with hematologic malignancies when platelet counts decline to 10,000/µL. However, fewer platelet transfusions might be required if they were limited to thrombocytopenic patients with clinically important bleeding (WHO grade 2), regardless of the platelet count.

To determine the feasibility and safety of this approach, German investigators conducted a prospective, open-label, multicenter study involving 391 patients receiving chemotherapy for acute myeloid leukemia (AML) or undergoing stem-cell transplantation (SCT) for hematological cancers. Patients were randomized to receive platelet infusions when their morning platelet counts were 10,000/µL (prophylactic group) or only when they experienced grade 2 or higher bleeding (therapeutic group). Patients were assessed twice daily and all new bleeding, headaches, or other cerebral symptoms were investigated. Results were as follows:

  • The therapeutic group required fewer transfusions than the prophylactic group (mean, 1.63 vs. 2.44; P<0.0001), but experienced a higher rate of bleeding (42% vs. 19%; P<0.0001), including more grade 4 bleeding (5% vs. 1%; P=0.02).
  • AML patients experienced more bleeding than SCT patients (37% vs. 18%; P<0.0001); only AML patients experienced grade 4 bleeding, including two episodes of fatal cerebral hemorrhages in the therapeutic group.
  • The therapeutic and prophylactic groups experienced similar overall survival, number of red blood cell transfusions, duration of thrombocytopenia, and number of days in the hospital.

Comment: The indications for platelet transfusions require continued review, and pegging their use to a specific platelet count might not always be appropriate (JW Oncol Hematol Feb 17 2010). As this study shows, thrombocytopenic SCT patients infrequently experienced major hemorrhages, so therapeutic platelet transfusion might be more appropriate for this population. In contrast, predicting bleeding does not seem possible in thrombocytopenic AML patients, even with careful monitoring. So platelet transfusions only for bleeding might be more appropriate for these patients.

Source: Journal Watch Oncology and Hematology

Radical Prostatectomy Confers No Mortality Benefit in Localized Cancer .

Radical prostatectomy does no better than observation in reducing overall or cancer-related mortality in patients with localized cancers, suggests a New England Journal of Medicine study. Editorialists note that the study was too small to be definitive.

Researchers randomized 731 patients diagnosed through prostate-specific antigen screening to either radical prostatectomy or observation. The primary outcome was all-cause mortality, and the secondary outcome was prostate cancer mortality.

After a median follow-up of 10 years, there was no advantage to prostatectomy over observation for either outcome, except among those with initial PSA values above 10 ng/mL. In these patients, prostatectomy was more advantageous.

Writing in Journal Watch Oncology and Hematology, Robert Dreicer agrees with NEJM‘s editorialists, who lament that the difficulty in recruiting patients led to an underpowered study. Dreicer sees these results as a prompt “to develop the next generation of studies to better identify and aggressively treat patients at risk.”

Source: NEJM