RxPG News : Non-Hodgkin's Lymphoma

PCBs, Furans May Factor in Risk of Non-Hodgkin Lymphoma

Fri, 02 Dec 2005 20:02:38 PST

( from http://www.rxpgnews.com ) Scientists have found some additional evidence that environmental exposure to polychlorinated biphenyls (PCBs) may be associated with non-Hodgkin lymphoma, according to a study published in the December 1 issue of Cancer Research.

By comparing blood levels of PCBs in 100 pairs of healthy volunteers and non-Hodgkin lymphoma patients, Anneclaire De Roos, Ph.D., assistant professor of epidemiology, Fred Hutchinson Cancer Research Center, and colleagues determined that high levels of three specific molecular forms of PCBs are linked to an increased risk of developing cancer that starts in patients lymph tissue.

The research also disclosed a potential increased risk of non-Hodgkin lymphoma associated with high blood levels of total dibenzofurans. Furans form as a by-product of waste incineration and other industrial processes and are also present in the environment at lower levels than PCBs.

This study strengthens the hypothesis that persistent organochlorines may be associated with risk of lymphoma, said Nathanial Rothman, a researcher in the National Cancer Institutes Division of Cancer Epidemiology and Genetics.

The furans are a new hypothesis, and the PCB findings provide us with some additional evidence, but these studies really need to be replicated broadly with much larger numbers of cases. Also, it is important to follow-up these findings in prospective cohort studies that collect blood samples from people when they are healthy, so that we can measure organochlorine levels before their disease develops.

Incidence of non-Hodgkin lymphoma has risen through-out the last half of the twentieth century, concurrent with the use and environmental dispersion of synthetic PCBs. Although their production has been banned for more than 25 years in the United States due to toxicological concerns, PCBs persist in the environment and remain in humans because they break down slowly.

Though they arent being produced any more we still detect them in the environment, but at lower levels than in the past, Rothman said.

Nonetheless, the presence of PCBs in the environment and even in the blood of humans doesnt mean that these compounds are cancer-causing substances, he cautioned.

There is still a good deal of uncertainty as to whether PCBs are actually causally associated with any cancer in humans, he said.

While their current report adds more evidence about PCBs and cancer, it was not designed to produce the smoking gun evidence that defines the molecular events induced by cellular exposure to PCBs resulting in initiation of cancer. Also, studies of workers with high occupational exposure to PCBs have not detected an excess of lymphoma, adding uncertainty to the relationship.

We believe our findings could provide an important clue to the cause of NHL, Rothman said. However, these associations need to be examined in other studies. If the relationship is consistently replicated, we need to carefully address whether or not PCBs or furans are likely to cause lymphoma, or if another risk factor that is associated with these chemicals could be the true causative agent.

Nearly 54,000 Americans will be diagnosed with non-Hodgkin lymphoma this year, according to the American Cancer Society. More than 19,000 will die from the disease. More men (23 of every 100,000) develop the lymphatic system cancer than women (16 per 100,000). Most non-Hodgkin lymphoma patients are mature adults. The average age at diagnosis is 60 years, with the average survival of patients with low-grade lymphomas about six to eight years after diagnosis. Some 30 percent of patients diagnosed with high-grade lymphomas are permanently cured after treatment, which varies by type of lymphoma and response to chemotherapies.

Tositumomab Brings New Hope for Refractory Non-Hodgkin's Lymphoma

Sat, 10 Sep 2005 23:01:38 PST

( from http://www.rxpgnews.com ) Health Canada has approved a new treatment that could offer hope for those who suffer from what is considered an incurable form of non-Hodgkin's lymphoma (NHL) and who have failed on, or relapsed following, other treatments. Health Canada approved Bexxar(TM) (tositumomab and iodine I 131 tositumomab) therapy for the treatment of patients with CD20 positive relapsed or refractory, low grade, follicular, or transformed non-Hodgkin's lymphoma, including patients with rituximab- refractory NHL.

"Bexxar represents an important new direction in cancer therapy," says Dr. Harold J. Olney, hematologist, medical oncologist and principal investigator for Bexxar's current Canadian clinical trial. "Bexxar is an NHL treatment that is tailored to administer a targeted and patient-specific therapeutic dose of radiation, thereby preventing either under or overdosing of radiation. For patients who have not responded or have relapsed following front line treatments, Bexxar is an important and welcome option."

Bexxar is the latest of a new generation of patient-tailored cancer treatments that specifically targets non-Hodgkin's lymphoma cells, while minimizing risk to surrounding healthy cells. Bexxar is given at a dose specific to individual patient characteristics, usually in an outpatient setting. Administered in a short treatment course, Bexxar can provide long- lasting responses in patients whose disease has not responded to other treatments. In clinical studies, approximately one in four patients on Bexxar were shown to have a durable complete response of greater than one year.

Bexxar was granted Health Canada's Priority Review status, which is reserved for new drugs that have the potential ability to address serious, life-threatening or severely debilitating illness or conditions for which there is an unmet medical need. Bexxar is expected to be available in Canada in October, 2005.

About Bexxar Therapy

Bexxar is a dual-action therapy that pairs the tumor-targeting ability of a cytotoxic (cancer killing) monoclonal antibody (tositumomab) and the therapeutic effect of patient-specific radiation (iodine-131) dosing. Antibodies (tositumomab) target and attach to cancer cells deep inside the tumor (antigen CD20 found on NHL cells). The radiation dose (iodine 131) then targets tumors with minimal risk to surrounding healthy cells.

Clinical Study Results

The efficacy of Bexxar therapy was examined in a multi-center, single-arm study of 40 patients with follicular NHL whose disease had relapsed following or had not responded to rituximab. The median age of patients in the study was 57 (range: 35-78) and the median number of prior chemotherapies was four (range: 1-11). Eighty-eight per cent of patients met the definition of rituximab refractory (defined as no response or a response of less than six months in duration). In these patients with rituximab refractory disease, 63 per cent of patients had a response to Bexxar, with a median duration of response of 25 months. Twenty-nine per cent of these patients had a complete response (no clinical signs of disease) to Bexxar. The median duration of complete responses had not been reached after a median follow up of 26 months.

The results of this study were supported by demonstration of durable objective responses (lasting more than one year) in one phase III and three other single-arm studies, enrolling 190 patients with rituximab-naive, follicular NHL, with or without transformation, who had relapsed following or were refractory to chemotherapy. In these studies, the overall response rates ranged from 47 per cent to 64 per cent and the median durations of response ranged from 12 to 18 months.

Side Effects

The most common adverse reactions occurring in the clinical trials included neutropenia, thrombocytopenia and anemia. Less common but severe reactions included pneumonia, pleural effusion and dehydration.

The most common non-hematologic side effects included asthenia (weakness), fever, nausea, infection and cough. Bexxar was associated with a risk of hypothyroidism and human anti-murine antibody (HAMA) formation. Certain chemotherapy agents and ionizing radiation have been associated with the development of myelodysplasia (MDS), secondary leukemia and solid tumors. MDS, secondary leukemia and solid tumors have also been observed in patients receiving Bexxar therapy.

Administration of Bexxar may result in infusion-related reactions that may be induced by the administration of foreign proteins. Hypersensitivity reactions occurred in six per cent of patients. Adjustments of the rate of infusion to control adverse reactions were required in seven per cent of patients.

Bexxar Therapy

Bexxar consists of four components administered in two steps over seven to fourteen days, usually on an outpatient basis. The first set of infusions includes the non-radioactive antibody, tositumomab, used to improve the distribution in the body of the subsequent radioactive antibody and increase its uptake in the tumor, followed by a dosimetric infusion, containing the antibody and a trace amount of radioactive iodine 131. This dosimetric step allows for visualization of the location of the radioisotope and the determination of the rate of clearance of radioactivity from the body by the use of gamma camera counts obtained at three time points. Clearance is dependent on factors such as tumor size and bone marrow involvement. From these determinations, the patient-specific amount of radioactivity necessary to deliver the targeted therapeutic total body dose of radiation can be calculated. Seven to fourteen days after the dosimetric step, the patient returns for the therapeutic step, which again includes two infusions, beginning with the non-radioactive antibody, but this time followed by the calculated patient-specific radioactivity needed to deliver the targeted total body dose of radiation.

About non-Hodgkin's Lymphoma

Non-Hodgkin's lymphoma is a form of cancer that affects the blood, bone marrow and lymphatic tissues. Unlike most major forms of cancer, both incidence and mortality rates of NHL are increasing. Incidence rates for NHL in Canada have more than doubled over the last thirty years and are among the highest in the world.(1) The Canadian Cancer Society estimates that 6,400 new cases will be diagnosed in 2005 and that 3,000 Canadians will die this year from the disease(2). Transformed non-Hodgkin's lymphoma can be an aggressive and difficult to treat form of follicular non-Hodgkin's lymphoma with a particularly poor prognosis.

People who drink alcohol have a lower risk of non-Hodgkin's lymphoma (NHL)

Mon, 15 Aug 2005 20:25:38 PST

( from http://www.rxpgnews.com ) People who drink alcohol have a lower risk of non-Hodgkin's lymphoma (NHL) than non-drinkers, researchers at Yale's Department of Epidemiology and Public Health (EPH) write in an article published in Lancet Oncology.

Led by former EPH graduate student Lindsay M. Morton of the National Cancer Institute, the research team found that the protective effect of alcohol did not vary by type of alcohol consumed, and did not increase along with alcohol consumption. However, the protective effect of alcohol did vary by NHL subtype, and was greatest for Burkitt's lymphoma. Age, sex, family history of NHL, and history of cigarette smoking did not reduce the effect of alcohol consumption on NHL risk.

The findings come at a time when NHL incidence is rising throughout the world. In developed countries, NHL is the sixth most common cancer in men and the eighth most common in women. Previous studies examining the relationship between alcohol consumption and NHL risk have been inconsistent, likely due to small sample size resulting from stratification by NHL subtype and type of alcohol consumed.

"This study with a large sample size allows us with sufficient statistical power to analyze the data by type of alcohol consumed and disease subtype," said principal investigator Tongzhang Zheng, associate professor of epidemiology at EPH. "The resulting study was a pooled analysis of original data from nine case-control studies in the International Lymphoma Epidemiology Consortium (InterLymph), with a pooled study population of 15,175."

Susan T. Mayne, a nutrition epidemiologist at EPH and an author on the study said that further studies are needed to confirm the findings and to determine whether certain lifestyle factors or alcohol's immunomodulatory effects explain the association between alcohol consumption and decreased NHL risk.

Other authors on the study included Yale Professor Theodore R. Holford. Authors from other institutions included Elizabeth A. Holly, Brian C.H. Chiu, Adele Seniori Costantini, Emanuele Stagnaro, Eleanor V. Willett, Luigino Dal Maso, Diego Serraino, Ellen T. Chang, Wendy Cozen, Scott Davis, Richard K. Severson, Leslie Bernstein, Fred R. Dee, James R. Cerhan, and Patricia Hartge.