Gentler Chemotherapy Before Stem Cell Transplant Causes Long-term Remission Of Follicular Lymphoma, Study Suggests

Treating relapsed follicular lymphoma patients with a milder chemotherapy regimen before they receive a blood stem cell transplant from a donor resulted in long-term complete remission for 45 of 47 patients in a clinical trial, researchers at The University of Texas M. D. Anderson Cancer Center report at the 49th annual meeting of the American Society of Hematology.

The two patients who had relapsed after the treatment regained a complete response after additional therapy.

"Our results show that this approach may actually be curative of follicular lymphoma," says lead author Issa Khouri, M.D., professor in M. D. Anderson's Department of Stem Cell Transplantation. "No other treatments produce this type of response."

The traditional treatment before receiving a matched stem cell donation consists of higher-dose chemotherapy that kills the lymphoma cells and shuts down the patient's own blood-producing stem cells - a process called myeloablation. While waiting for the donor's stem cells to engraft in the bone marrow and to begin producing blood, patients are vulnerable to infection, bleeding, and anemia.

Early research by Khouri and colleagues indicated that using a nonmyeloablative chemotherapy approach could control the lymphoma while sparing patients the side effects of high-dose chemotherapy. The transplanted blood stem cells launch an immune system attack on the lymphoma, a process called graft-vs.-lymphoma immunity.

"Our early results were encouraging. But with follicular lymphoma you need a long follow-up to see if the results hold," Khouri says. "This disease tends to recur later on, sometimes years after chemotherapy."

All patients in the present trial have been followed for at least five years, some for up to nine years. Trial patients had received 2 to 7 different chemotherapy regimens. Eight had received transplants of their own stem cells. At transplantation, 29 were in partial remission and 18 were in complete remission.

All 47 achieved complete remission after receiving matched blood stem cells from donors. One patient relapsed at 18 months. After receiving a donor lymphocyte infusion, the patient began a continuous complete response at 24 months. The other patient relapsed at 20 months and was found to have graft failure. Since treatment with rituximab, this patient has been in complete remission for four years.

Seven patients died during the trial, none from follicular lymphoma, Khouri notes. The 40 remaining patients all remain in remission. Overall survival at six years is 85 percent and current progression-free survival is 83 percent.

Acute graft-vs.-host disease (GVHD) arose in 11 percent of patients. Another 51 percent had chronic graft-vs.-host disease. GVHD was treated with immunosuppressive therapy. Khouri notes that only five patients in the study group remain on immunosuppressive therapy.

Long-term follow-up also allowed researchers to thoroughly gauge side effects, or toxicity, of the non-myeloablative approach. "It reduces toxicity significantly," Khouri says. "Even elderly patients can have this done."

Patients received fludarabine, cyclophosphamide and rituximab for three days before transplantation. Tacrolimus and methotrexate were used to prevent graft-vs.-host disease.

Follicular lymphoma is a Non-Hodgkin lymphoma, with about 12,000 new cases diagnosed annually.

Co-authors with Khouri are Rima M. Saliba, Martin Korbling, Chitra Hosing, Luis Fayad, Ming S. Lee, Felipe Samaniego, Barry I. Samuels, Daniel Couriel, Fredrick Hagemeister, Peter McLaughlin and Richard Champlin, all of M. D. Anderson.

Adapted from materials provided by University of Texas M. D. Anderson Cancer Center, via EurekAlert!, a service of AAAS.

Oophorectomy Linked with Cognitive Problems

According to the results of a study published in the journal Neurology, premenopausal women who have one or both ovaries removed face an increased risk of cognitive problems or dementia later in life. Use of hormone replacement therapy until the age of natural menopause appeared to reduce this risk.

Women at very high risk of developing breast or ovarian cancer as a result of a hereditary cancer syndrome have the options of undergoing close surveillance for the development of cancer or of undergoing prophylactic (preventive) surgery to remove the breasts and/or ovaries.

A bilateral prophylactic salpingo-oophorectomy (BPSO) is a surgical procedure in which both the ovaries and the fallopian tubes are removed. In addition to reducing the risk of ovarian cancer, this procedure also reduces the risk of breast cancer; hormones produced by the ovaries (such as estrogen) contribute to the growth of many breast cancers.

Because estrogen may have a beneficial effect on cognitive function, it’s possible that removal of one or both ovaries before menopause (when the ovaries are still producing estrogen) may have a negative impact on cognitive function. To explore this possibility, researchers conducted a study among 813 women who had one ovary removed before menopause, 676 women who had both ovaries removed before menopause, and a comparison group of 1,472 women who still had both ovaries.[1]

Among the women who had one or both ovaries removed, the reasons for ovary removal were either treatment of a benign condition (such as ovarian cysts) or prevention of cancer. Women who already had cancer were excluded from the study.

The occurrence of cognitive impairment or dementia was assessed over a follow-up period of roughly 25 years.

Removal of either one or both ovaries was linked with an increased risk of cognitive impairment or dementia. Risk was highest among the women who were the youngest at the time of their oophorectomy.
Among women who had both ovaries removed before the age of 49, those who used hormone replacement therapy until at least the age of 50 did not have an increased risk of cognitive impairment or dementia.
The researchers conclude that unilateral or bilateral oophorectomy before menopause appears to increase the risk of cognitive impairment or dementia. Although use of hormone replacement therapy until the age of natural menopause may decrease this risk, an accompanying editorial notes that many questions remain about the relationship between estrogen therapy and cognition.[2]

Reference:

[1] Rocca WA, Bower JH, Maraganore DM et al. Increased risk of cognitive impairment or dementia in women who underwent oophorectomy before menopause. Neurology. 2007;69:1074-83.

[2] Hogervorst E, Bandelow St. Should surgical menopause women be treated with estrogens to decrease the risk of dementia? Neurology. 2007;69:1070-1071.

Related News: Risk of Death with Preventive Oophorectomy Evaluated (9/18/2006)

Cancer Mortality Rates Vary by Education Level

According to the results of a study published in the Journal of the National Cancer Institute, a lower level of education is linked with an increased risk of cancer death among African-American and White men and women.

Many health outcomes—including overall risk of death—are known to vary by race and socioeconomic status. Relatively few studies, however, have assessed how race and socioeconomic status interact to influence cancer incidence and mortality in the U.S.

To evaluate the effect of education on cancer mortality among African-American and White men and women, researchers collected information from death certificates and the U.S. Bureau of the Census for the year 2001. Information was collected about residents of 47 states and Washington, D.C.

The study included 111,376,196 individuals between the ages of 25 and 64. This population experienced 137,708 cancer deaths during 2001.

Among both White and African-American men, overall risk of cancer death was more than twice as high among those with 12 or fewer years of education compared with those with more than 12 years of education.
African-American women with 12 or fewer years of education were 43% more likely to die of cancer than African-American women with more than 12 years of education.
White women with 12 or fewer years of education were 76% more likely to die of cancer than White women with more than 12 years of education.
In addition to overall risk of cancer death, the risks of death from four specific types of cancer (lung, breast, colorectal, and prostate) were also higher among less educated people than among more educated people. The finding that breast cancer mortality is higher among less educated women than among more educated women is different than what has been reported previously but was observed among both African-American and White women.
The researchers conclude that cancer death rates vary considerably by level of education, with a higher rate of death among those with the least education. Because the study was restricted to African Americans and Whites between the ages of 25 and 64, these results may not be applicable to other racial groups or to older individuals.

Reference: Albano JD, Ward E, Jemal A et al. Cancer mortality in the United States by education level and race. Journal of the National Cancer Institute. 2007;99:1384-94.

Pain Still Occurs in Majority of Cancer Patients

According to an article recently published in Annals of Oncology, over half of patients diagnosed with cancer experience pain, despite guidelines that have been adopted for the reduction of pain. Patients diagnosed with advanced or terminal cancer experience an even higher rate of pain, with those diagnosed with head and neck cancer experiencing the most pain.

Pain is one of the most feared consequences associated with the diagnosis of cancer. As cancer becomes more advanced, it grows and spreads throughout the body. This growth crowds organs, tissues, vasculature (veins, arteries, or capillaries), lymph nodes (part of the immune system), and/or bones. The cancerous growth itself can cause pain as it places pressure on nerves and it can interfere with normal biological processes, causing a blockage and/or buildup of fluid or other components.

Pain has been recognized as an important focus of treatment among cancer patients. Guidelines have been established by healthcare panels for the treatment of pain, depending upon severity and other existing medical conditions of the patient. Often, patients with terminal cancer remain on pain medications throughout the duration of treatment once their disease has become advanced. In fact, controlling pain is one of the top priorities in end-of-life patient care. However, data regarding the prevalence of pain among patients with cancer remain limited.

Researchers from the Netherlands recently conducted a clinical study to review data regarding the prevalence of pain among cancer patients. The data included a literature review regarding pain in different disease stages and different types of cancer. Fifty-two studies were included in this analysis.

33% of patients who had undergone curative therapy for their cancer reported pain following therapy.

59% of patients undergoing treatment for cancer reported pain.

64% of patients with advanced, metastatic, or terminal cancer reported pain.

Patients diagnosed with head and neck cancer reported the greatest incidence of pain.
Over half of all patients diagnosed with cancer reported overall pain, with more than one-third grading their pain as moderate or severe.
The researchers concluded that, despite guidelines to control pain in cancer patients, “cancer pain still is a major problem.” Patients diagnosed with cancer who are experiencing pain should speak with their healthcare provider regarding the prevention or control of pain.

Reference: van den Beuken-van Everdingen MHJ, de Rijke J, Kessels A, et al. Prevalence of pain in patients with cancer: a systematic review of the past 40 years. Annals of Oncology. 2007; 18; 1437-1449.

Avastin® Increases Risk of Blood Clots in Arteries

According to a combined analysis of five clinical trials, treatment of metastatic colorectal cancer, breast cancer, or non–small lung cancer with a combination of Avastin and chemotherapy results in a higher risk of arterial blood clots than treatment with chemotherapy alone. These results were published in the Journal of the National Cancer Institute.

Avastin is a drug that blocks a protein known as vascular endothelial growth factor (VEGF). VEGF stimulates the growth of new blood vessels.

Drugs that interfere with VEGF can slow or stop the growth of cancer cells. In addition, drugs that interfere with VEGF may improve the delivery of chemotherapy to cancer cells by normalizing blood supply.

While clinical trials have indicated that the combination of Avastin and chemotherapy improves survival among patients with certain types of metastatic cancer, some of these trials have also suggested that this treatment combination may increase the risk of blood clots in the arteries.

To provide additional information about the risk of blood clots in patients treated with Avastin and chemotherapy, researchers combined information from five clinical trials. These trials enrolled a total of 1,745 patients with metastatic colorectal, breast, or non–small cell lung cancer. Each of the trials compared the combination of Avastin and chemotherapy to chemotherapy alone.

Patients were classified as having an arterial blood clot if they experienced one of the following adverse events: angina pectoris, arterial thrombosis, cerebral infarct, cerebral ischemia, cerebrovascular accident, myocardial infarction, or myocardial ischemia.

Risk of a blood clot in the artery was 3.1 per 100 people per year among patients treated with chemotherapy alone and increased to 5.5 per 100 people per year among patients treated with Avastin and chemotherapy.
Other factors that increased the risk of arterial blood clots were older age (age 65 or older) and history of arterial blood clots.
Risk of a blood clot in a vein was not increased among patients treated with Avastin and chemotherapy.
The researchers conclude that compared to chemotherapy alone, the combination of chemotherapy and Avastin increases the risk of blood clots in the arteries.

Reference: Scappaticci FA, Skillings JR, Holden SN et al. Arterial thromboembolic events in patients with metastatic carcinoma treated with chemotherapy and bevacizumab. Journal of the National Cancer Institute. 2007;99:1232-9.

Smoking Linked to Head and Neck Cancer in Women

According to an article recently published in the journal Cancer, women have a higher risk than men that smoking will increase their risk of developing head and neck cancer.

Head and neck cancer refers to several types of cancers including, but not limited to, cancer of the tongue, gums, oral cavity, nasal cavity, voice box, and back of the throat. Although men have a higher rate of head and neck cancer than women, incidence of head and neck cancer in women has been increasing significantly throughout the world.

Once head and neck cancer has spread from its site of origin, survival rates decrease dramatically. As well, treatment for more advanced head and neck cancer is often associated with significant declines in quality of life, as surgery often disfigures patients and/or severely impairs their ability to perform basic functions such as chew, swallow, or speak. Radiation that includes the salivary glands may also cause extremely dry mouth or sores in the mouth.

Smoking has already been established as a risk factor for developing head and neck cancer. However, data is limited about female smokers and their particular risk of head and neck cancer. Researchers affiliated with the National Cancer Institute recently conducted a clinical study to explore the association between cigarette smoking and head and neck cancer in women. This study included over 476,000 men and women, aged 50–71 years. From 1995 through 2000, 584 men and 175 women were diagnosed with cancer.

Overall, men had a higher incidence of head and neck cancer than women.
Smoking, however, caused a greater proportion of head and neck cancer in women than in men (75% versus 45%, respectively).
The researchers concluded: “Cigarette smoking is a strong risk factor for head and neck cancer in both men and women. Incidence rates of head and neck cancer were higher in male smokers than female smokers, but smoking may explain a higher proportion of head and neck cancer in women than in men.” Individuals who smoke may wish to speak with their physician regarding smoking cessation programs.

Reference: Freedman N, Abnet C, Leitzmann M, et al. Prospective investigation of the cigarette smoking-head and neck cancer association by sex. Cancer [early online publication]. August 10 2007. DOI: 10.1002/cncr.22957.

Fludara® plus Cytoxan® New Standard of Care for Chronic Lymphocytic Leukemia

According to an article recently published in The Lancet, the chemotherapy combination consisting of Fludara® (fludarabine) plus Cytoxan® (cyclophosphamide) significantly improves progression-free survival compared to Fludara alone without compromising quality of life in the treatment of chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL) is the most common form of adult leukemia. The American Cancer Society estimates that approximately 8,000 people will be diagnosed with CLL this year. Currently, there are approximately 60,000 people in the U.S. living with CLL.

CLL is characterized by the production of atypical lymphocytes. Lymphocytes are specialized immune cells that exist in two forms: B- and T-cells. These cells are produced in the bone marrow and each serves a specific function in aiding the body fight infection.

The large majority of CLL cases involve mature B-lymphocytes that tend to live much longer than normal. B-lymphocytes accumulate in the blood, bone marrow, lymph nodes, and spleen. This results in overcrowding of these areas and suppression of the formation and function of blood and immune cells. Additionally, the cancerous lymphocytes themselves do not function normally, leading to a further reduction in the body’s ability to fight infection.

There are several chemotherapy agents available for the treatment of CLL; three of these are Fludara, Cytoxan, and chlorambucil. Results from prior studies have demonstrated high anticancer responses with the regimen including both Fludara and Cytoxan. Researchers recently conducted a clinical trial to directly compare treatment for CLL with Fludara alone, Fludara plus Cytoxan, or chlorambucil. This trial included 777 patients who received one of these treatment options.

Overall anticancer responses were achieved in 94% of patients treated with Fludara plus Cytoxan, 80% of patients treated with Fludara only, and 72% for patients treated with chlorambucil.
Complete disappearances of detectable cancer occurred in 38% of patients treated with Fludara plus Cytoxan, compared with only 15% of patients treated with Fludara only.
At five years progression-free survival was 36% for patients treated with Fludara plus Cytoxan, compared with only 10% for patients treated with Fludara or chlorambucil.
Overall survival was not significantly different between patients in any treatment group.
Quality of life was reported to be better among patients who achieved anticancer responses from treatment; however, quality of life did not differ significantly between any treatment groups.
The researchers concluded that the combination of Fludara plus Cytoxan “should now become the standard treatment for chronic lymphocytic leukaemia and the basis for new protocols that incorporate monoclonal antibodies.” Patients diagnosed with CLL may wish to speak with their physician regarding their individual risks and benefits of all treatment options.

Reference: Catovsky D, Richards S, Matutes E, et al. Assessment of fludarabine plus cyclophosphamide for patients with chronic lymphocytic leukaemia (the LRF CLL4 Trial): a randomised controlled trial. The Lancet. 2007;379: 230-239.