Pancreatic neuroendocrine tumors are a relatively uncommon type of cancer that develops in the hormone-producing cells of the pancreas.

Sutent is an oral targeted agent that works by inhibiting multiple biologic pathways involved in the growth, replication, and spread of cancer cells. It has been shown to be effective in the treatment of selected patients with kidney cancer or gastrointestinal stromal tumors, and is also being evaluated in the treatment of other types of cancer.

To evaluate Sutent for the treatment of advanced pancreatic neuroendocrine tumors, researchers conducted a Phase III clinical trial among 171 patients who had experienced cancer progression. Half the patients were treated with Sutent, and half were treated with a placebo.

• Progression-free survival was 11.4 months among patients treated with Sutent and 5.5 months among patients treated with placebo.
• Patients treated with Sutent also experienced better overall survival than patients treated with placebo.
• The most common serious side effect of Sutent was neutropenia (a low white blood cell count), which affected 12% of patients.

These results suggest that Sutent may improve outcomes among patients with advanced pancreatic neuroendocrine tumors.

Reference: Raymond E, Niccoli-Sire P, Bang Y et al. Updated results of the phase III trial of sunitinib (SU) versus placebo (PBO) for treatment of advanced pancreatic neuroendocrine tumors (NET). Presented at the 2010 ASCO Gastrointestinal Cancers Symposium. January 22-24, 2010, Orlando, FL. Abstract 127.

Gene expression profiling explores the patterns of genes that are active in tumor cells. Studies suggest that gene expression may provide important information about prognosis or likely response to treatment in several types of cancer. For example, among women with early-stage, estrogen receptor-positive breast cancer, the Oncotype DX® breast cancer test has been shown to predict the likelihood of cancer recurrence and the likelihood of benefit from chemotherapy. As a result, the test has been added to medical guidelines for early-stage breast cancer.

A similar test may provide important information for patients with Stage II colon cancer. Stage II colon cancer refers to cancer that extends through the wall of the colon but has not invaded lymph nodes or spread to distant parts of the body. Many patients with this stage of disease have good outcomes with surgery alone, and routine adjuvant (post-surgery) chemotherapy is not currently recommended for Stage II colon cancer. Chemotherapy may, however, be considered for Stage II patients with a higher risk of cancer recurrence.

In the current analysis, the Oncotype DX colon cancer Recurrence Score and other factors were evaluated in 657 patients with Stage II colon cancer treated with surgery alone.

• Risk of cancer recurrence varied by the Recurrence Score as well as the number of lymph nodes examined. Patients with higher Recurrence Scores had a higher risk of cancer recurrence. Patients also had a higher risk of recurrence if they had fewer lymph nodes examined.

The researchers concluded: “Number of nodes examined and [Recurrence Score] are independent predictors of recurrence in stage II colon cancer following surgery, and both should be considered when assessing individual recurrence risk.”

The Oncotype DX colon cancer test is the first commercially available gene expression test for the assessment of recurrence risk in Stage II colon cancer.

Reference: Gray RG, Quirke P, Handley K et al. Correlation of number of nodes examined and the 12-gene colon cancer recurrence score with recurrence in stage II colon cancer patients from QUASAR. Presented at the 2010 ASCO Gastrointestinal Cancers Symposium. January 22-24, 2010, Orlando, FL. Abstract 331.

Mortality rates from ovarian cancer continue to be high, largely because many women are not diagnosed with the disease until it has reached an advanced stage. In an attempt to improve survival by detecting the disease at an earlier stage, researchers are evaluating potential biological markers of the disease. Levels of certain proteins in the blood, for example, may be higher in women with ovarian cancer than in women without ovarian cancer. If these markers reliably distinguish women with and without ovarian cancer, and if the markers can be identified early in cancer development (before the cancer would typically be diagnosed clinically), then they may contribute to the early detection of ovarian cancer.

The current study evaluated six potential biological markers of ovarian cancer: CA125, human epididymis protein 4 (HE4), mesothelin, B7-H4, decoy receptor 3 (DcR3), and spondin-2.[1] Levels of each were measured in serum samples taken from 34 women who were later diagnosed with ovarian cancer, and 70 women who remained free of ovarian cancer.

Levels of three of these markers—CA125, HE4, and mesothelin—began to increase slightly three years before the diagnosis of ovarian cancer. Levels didn’t become markedly elevated until the last year prior to diagnosis, however, and the overall ability of these markers to reliably identify women with ovarian cancer was limited.

Although the results of this study suggest that these particular markers may do little to increase early detection of ovarian cancer, this type of research continues to hold promise. An accompanying editorial notes that these results “are not the last word in serum markers or in combinations of markers. Serum markers likely will form a key element in any screening regimen…”[2]

References:

[2] Hartge P. Designing early detection programs for ovarian cancer. Journal of the National Cancer Institute. 2010;102:3-4.

Colorectal cancer is the second leading cause of cancer death in the United States. Treatment of advanced colorectal cancer often involves combination chemotherapy.

Avastin is a targeted therapy that blocks a protein known as VEGF. VEGF plays a key role in the development of new blood vessels. By blocking VEGF, Avastin deprives the cancer of nutrients and oxygen and inhibits its growth. Avastin’s effects on blood vessels may also improve the delivery of chemotherapy to the tumor. Avastin has been approved for the treatment of selected patients with several types of cancer, including colorectal cancer.

To summarize available information about Avastin in advanced colorectal cancer, researchers evaluated information from five clinical trials. The studies compared chemotherapy plus Avastin to chemotherapy alone for first- or second-line treatment.

• The addition of Avastin to chemotherapy improved overall survival by 21% and improved progression-free survival by 37%.
• The most common side effects related to Avastin included high blood pressure, protein in the urine, bleeding, and blood clots.

The results of this review confirm that the addition of Avastin to chemotherapy improves overall survival and delays cancer progression among patients with advanced colorectal cancer. Avastin also, however, increases the occurrence of side effects.

The researchers note that the benefit of Avastin may vary depending on the specific chemotherapy regimen that is used.

Reference: Welch S, Spithoff K, Rumble RB et al. Bevacizumab combined with chemotherapy for patients with advanced colorectal cancer: a systematic review. Annals of Oncology [early online publication]. November 25, 2009.

Thyroid cancer is treated by surgery and 131Iodine. Patients who fail these therapies respond poorly to radiotherapy and chemotherapy. Thus, new treatments are needed for patients who fail conventional therapy. Recent studies have shown that the targeted therapies Nexavar® (sorafenib) and axitinib have activity in patients with advanced thyroid cancer.

Zactima is a targeted therapy with several mechanisms of action. Among other things, it inhibits a protein known as RET that plays an important role in hereditary medullary thyroid cancer.

To explore the efficacy of Zactima for the treatment of advanced, hereditary medullary thyroid cancer, researchers conducted a Phase II clinical trial among 30 patients with locally advanced or metastatic cancer that could not be surgically removed.

Patients were treated with Zactima 300 mg/day.

• 20% of patients experienced a partial reduction in detectable cancer.
• An additional 53% of patients experienced stable disease that lasted for at least 24 weeks.
• The most common side effects of treatment were diarrhea (70%), rash (67%), fatigue (63%), and nausea (63%).

These results, along with previous results for Nexavar and axitinib, suggest that targeted drugs may play an important role in the treatment of thyroid cancers.

Reference: Wells SA, Gosnell JE, Gagel RF et al. Vandetanib for the treatment of patients with locally advanced or metastatic hereditary medullary thyroid cancer. Journal of Clinical Oncology [early online publication]. January 11, 2010.

Oncotype DX is a genomic test that has been shown to predict the likelihood of distant cancer recurrence and the likelihood of chemotherapy benefit in women with early-stage, estrogen receptor-positive breast cancer that is treated with hormonal therapy. The test evaluates the activity of 21 genes from a sample of the patient’s cancer to determine the patient’s Recurrence Score. Oncotype DX has been added to U.S. medical guidelines for early-stage breast cancer.

Although the Oncotype DX Recurrence Score has been shown to predict the risk of distant cancer recurrence, there has been less information about whether it also predicts risk of local or regional recurrence (recurrence in or near the breast).

To evaluate the Recurrence Score in relation to risk of local and regional breast cancer recurrence, researchers evaluated information from 895 women treated with tamoxifen [Nolvadex®], 355 women treated with placebo, and 424 patients treated with chemotherapy plus tamoxifen. All of the women had node-negative, estrogen receptor-positive breast cancer.

• Among women treated with tamoxifen, 10-year risk of local or regional cancer recurrence was 4.3% among women with a low Recurrence Score, 7.2% among women with an intermediate Recurrence Score, and 15.8% among those with a high Recurrence Score. The Recurrence Score also predicted risk of local or regional recurrence among women treated with placebo and women treated with chemotherapy and tamoxifen.

These results indicate that in addition to predicting the risk of distant cancer recurrence, the Recurrence Score also predicts the risk of local or regional cancer recurrence in women with node-negative, estrogen receptor-positive breast cancer.

Reference: Mamounas EP, Tang G, Fisher B et al. Association between the 21-gene recurrence score assay and risk of locoregional recurrence in node-negative, estrogen receptor-positive breast cancer: results from NSABP B-14 and NSABP B-20. Journal of Clinical Oncology. [early online publication] January 11, 2010.

The Oncotype DX test measures the expression of 21 genes in a sample of tumor tissue and generates a Recurrence Score. The Recurrence Score predicts the magnitude of chemotherapy benefit and the likelihood of breast cancer recurrence for women with early-stage, estrogen receptor-positive breast cancer.

To explore how use of the Oncotype DX test influences oncologist and patient treatment decisions and satisfaction, researchers collected information from 89 patients treated by 17 medical oncologists. Information about adjuvant treatment plan was collected before and after obtaining the Oncotype DX Recurrence Score.

• Based on the Recurrence Score, the oncologist’s treatment recommendation changed for 31.5% of patients. The most common change was from chemotherapy plus hormonal therapy to hormonal therapy alone.
• Recurrence Score results increased oncologist confidence in the treatment plan in 76% of the cases.
• 27% of patients changed their treatment decision based on the Recurrence Score.
• Patient anxiety was lower after receipt of the Recurrence Score results.

These results provide additional evidence that Recurrence Score results can influence treatment recommendations and treatment decisions for women with early breast cancer, and can help relieve patient anxiety.

Reference: Lo SS, Mumby PB, Norton J et al. Prospective multicenter study of the impact of the 21-gene recurrence score assay on medical oncologist and patient adjuvant breast cancer treatment selection. Journal of Clinical Oncology [early online publication]. January 11, 2009.

Multiple myeloma is a cancer of plasma cells. Plasma cells are a special type of white blood cell that are part of the body’s immune system. Plasma cells normally live in the bone marrow and make proteins, called antibodies, that circulate in the blood and help fight certain types of infections. Plasma cells also play a role in the maintenance of bone, by secretion of a hormone called osteoclast-activating factor. Patients with multiple myeloma have increased numbers of abnormal plasma cells that may produce increased quantities of dysfunctional antibodies detectable in the blood and/or urine.

Over the past two decades, there has been marked improvement in overall survival of patients with multiple myeloma. This improvement in survival has been due to the adoption of single or tandem, melphalan-based autologous stem cell transplants in younger, more fit patients, as well as the development of new drugs such as Thalomid® (thalidomide), Revlimid, and Velcade. These new drugs have improved outcomes of patients not suitable for stem cell transplantation and are now beginning to have an impact on transplant patients as well.

The current study involved 102 newly diagnosed multiple myeloma patients between the ages of 65 and 75. Induction therapy was a combination of Velcade, Doxil® (liposomal doxorubicin), and dexamethasone. All patients were scheduled to receive tandem, reduced-intensity, autologous stem cell transplants. The dose of melphalan was reduced from the standard 200 mg/m2 to 100 mg/m2. Four cycles of Revlimid were given for consolidation followed by Revlimid maintenance.

• After induction therapy 58% of patients had a very good partial response (VGPR) or better, with a 13% complete response (CR) rate.
• After transplantation, 82% had a VGPR or better, with a CR rate of 38%.
• After Revlimid maintenance, 86% had a VGPR or better, with a CR rate of 66%.
• Two-year progression-free survival was 69%.
• Two-year overall survival was 86%.

This study shows that tandem autologous transplants can be administered to myeloma patients between the ages of 65 and 75 years. The addition of Revlimid and Velcade also appears to improve outcomes in this group of patients. The researchers recommend further testing of this treatment approach in Phase III clinical trials.

Reference: Palumbo A, Gay F, Falco P, et al. Bortezomib as induction before autologous transplantation, followed by lenalidomide as consolidation-maintenance in untreated multiple myeloma. Journal of Clinical Oncology [early online publication]. January 4, 2010.

Mammograms (X-ray images of the breasts) are commonly used to screen women for breast cancer. The goal of screening mammography is to reduce breast cancer mortality by detecting breast cancer at an early stage.

The age at which mammographic screening should begin has recently been a subject of debate. The American Cancer Society continues to recommend that women at average risk of breast cancer begin mammographic screening at the age of 40.[1] The U.S. Preventive Services Task Force, however, recently recommended against routine mammographic screening of women in their 40s, noting that the decision to begin screening women in this age group “should be an individual one and take patient context into account, including the patient’s values regarding specific benefits and harms.”[2]

Two other groups that have recently added their voices to the discussion are the American College of Radiology and the Society of Breast Imaging.[3] These groups continue to recommend that women at average risk of breast cancer begin annual mammographic screening at the age of 40. The groups also note that women at high risk of breast cancer, such as those with certain BRCA1 or BRCA2 mutations, should begin screening at an earlier age, and should be screened with breast magnetic resonance imaging (MRI) in addition to mammography.

In light of the recent debate concerning when to begin screening mammography, women are encouraged to talk with their physician about the screening approach that’s right for them.

References:

[2] U.S. Preventive Services Task Force. Screening for Breast Cancer. Available at: http://www.ahrq.gov/clinic/USpstf/uspsbrca.htm Accessed January 6, 2010.

[3] Lee CH, Dershaw D, Kopans D et al. Breast cancer screening with imaging: recommendations from the Society of Breast Imaging and the ACR on the use of mammography, breast MRI, breast ultrasound, and other technologies for the detection of clinically occult breast cancer. Journal of the American College of Radiology. 2010;7:18-27.

Chronic lymphocytic leukemia is the most common adult leukemia with over 15,000 new cases per year in the United States and almost 5,000 deaths. CLL is not a rapidly growing cancer, but the abnormal cells accumulate in blood, bone marrow, lymph nodes, and spleen, resulting in enlargement of these organs and decreased bone marrow and immune function.

Treanda is a chemotherapy agent that combines the action of two types of agents, which attack cancerous cells through distinct pathways. In addition to being approved for CLL and relapsed non-Hodgkin’s lymphoma, Treanda is also being evaluated in clinical trials for the treatment of other types of cancer.

Rituxan is a targeted therapy that binds to a marker known as CD20 on the surface of B-cells. This binding prompts the immune system to destroy the cell, and may also have direct anticancer effects on the cell. Rituxan is commonly used in the treatment of non-Hodgkin’s lymphoma, and studies suggest that it’s also active against CLL.

The combination of Treanda and Rituxan has produced promising results among patients with previously treated CLL. To evaluate the combination of Treanda and Rituxan in the initial treatment of patients with advanced CLL, researchers in Germany conducted a Phase II clinical trial among 144 patients.

• Overall response rate was 91%, with 33% of patients experiencing a complete remission.
• 2.6% of patients died as a result of treatment.
• At 18 months, 76% of patients were still in remission.

These results suggest that the combination of Treanda and Rituxan may be safe and effective for the initial treatment of advanced CLL. This combination is being further evaluated in Phase III clinical trials.

Reference:

Fischer K, Cramer P, Stilgenbauer S, et al. Bendamustine combined with rituximab (BR) in first-line therapy of advanced CLL: A multicenter phase II trial of the German CLL Study Group (GCLLSG). Blood 2009;114:89, abstract number 205.