Healthcare Industry News: Leucovorin
News Release - February 23, 2010
Phase III Study of Avastin Plus Chemotherapy in Advanced Stomach Cancer Did Not Meet Primary EndpointSOUTH SAN FRANCISCO, Calif.--(HSMN NewsFeed)--Genentech, Inc., a wholly owned member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced that a Phase III study (AVAGAST) did not meet its primary endpoint of showing Avastin® (bevacizumab) plus Xeloda® (capecitabine) or 5-FU and cisplatin chemotherapy extended the lives of people with inoperable or advanced stomach (gastric) cancer, compared to chemotherapy alone. Adverse events in the trial were consistent with those previously reported for Avastin and no new safety signals have been observed to date. Data from the study will be submitted for presentation at the 2010 American Society of Clinical Oncology (ASCO) annual meeting, June 4 to 8, 2010.
“We are disappointed with these results because treatment options for stomach cancer are limited. However, we look forward to sharing the data with the medical community, including secondary endpoints,” said Hal Barron, M.D., executive vice president, Global Development and chief medical officer. “We are committed to developing medicines for people with stomach cancer, including Herceptin and Xeloda.”
These findings do not impact Avastin’s approved uses or its development program. Avastin is being studied worldwide in more than 450 clinical trials for multiple types of cancer.
About AVAGAST (AVF4200g)
AVAGAST is a multicenter, randomized, double-blind, placebo-controlled Phase III study designed to evaluate Avastin plus Xeloda® (capecitabine) or 5-FU and cisplatin chemotherapy compared to Xeloda or 5-FU and cisplatin chemotherapy alone in 774 patients with inoperable, locally advanced or metastatic cancer of the stomach or gastroesophageal junction. Patients in the study had received no prior treatment for advanced or metastatic stomach cancer. The primary endpoint of the study is overall survival. Secondary endpoints of the study include progression free survival, time to progression, overall response rate, duration of response during first line therapy, disease control rate and safety.
Information on Avastin, Xeloda and Herceptin® (trastuzumab)
Avastin in combination with intravenous 5-FU-based chemotherapy is indicated for first- or second-line treatment of patients with metastatic carcinoma of the colon or rectum.
Avastin Boxed WARNINGS and Additional Important Safety Information
People treated with Avastin may experience side effects. In clinical trials, some people treated with Avastin experienced serious and sometimes fatal side effects, including:
Gastrointestinal (GI) perforation: Treatment with Avastin can result in the development of a potentially serious side effect called GI perforation, which is the development of a hole in the stomach, small intestine or large intestine. In clinical trials, this side effect occurred in more people who received Avastin than in the comparison group (0.3 percent to 2.4 percent). In some cases, GI perforation resulted in fatality.
Surgery and wound healing problems: Treatment with Avastin can lead to slow or incomplete wound healing (for example, when a surgical incision has trouble healing or staying closed). In some cases, this event resulted in fatality. Surgery and wound healing problems occurred more often in people who received Avastin than in the comparison group. Avastin therapy should not be started for at least 28 days after surgery and until the surgical wound is fully healed. The length of time between stopping Avastin and having voluntary surgery without the risk of having surgery and wound healing problems following surgery has not been determined.
Severe bleeding: Treatment with Avastin can result in serious bleeding, including coughing up blood, bleeding in the stomach, vomiting of blood, bleeding in the brain, nosebleeds and vaginal bleeding. These events occurred up to five times more often in people who received Avastin. Across cancer types, 1.2 percent to 4.6 percent of people who received Avastin experienced severe to fatal bleeding. People who have recently coughed up blood (greater than or equal to a half teaspoon of red blood) or have serious bleeding should not receive Avastin.
In clinical trials for different cancer types, there were additional serious and sometimes fatal side effects that occurred in more people who received Avastin than in those in the comparison group. The formation of an abnormal passage from parts of the body to another part (non-GI fistula formation) was seen in 0.3 percent or less of people. Severe to life-threatening stroke or heart problems were seen in 2.4 percent of people. Too much protein in the urine, which led to kidney problems, was seen in less than 1 percent of people. Additional serious side effects that occurred in more people who received Avastin than those in the comparison group included severe to life-threatening high blood pressure, which was seen in 5 percent to 18 percent of people, and nervous system and vision disturbances (reversible posterior leukoencephalopathy syndrome), which was seen in less than 0.1 percent of people. Infusion reactions with the first dose of Avastin were uncommon and occurred in less than 3 percent of people and severe reactions occurred in 0.2 percent of people.
Common side effects that occurred in more than 10 percent of people who received Avastin for different cancer types, and at least twice the rate of the comparison group, were nosebleeds, headache, high blood pressure, inflammation of the nose, too much protein in the urine, taste change, dry skin, rectal bleeding, tear production disorder, back pain and inflammation of the skin (exfoliative dermatitis). Across all trials, treatment with Avastin was permanently stopped in 8.4 percent to 21 percent of people because of side effects.
Avastin may impair fertility. Patients who are pregnant or thinking of becoming pregnant should talk with their doctor about the potential risk of loss of the pregnancy or the potential risk of Avastin to the fetus during and following Avastin therapy, and the need to continue an effective birth control method for at least six months following the last dose of Avastin.
First-line Metastatic Colorectal Cancer: In the first-line metastatic colorectal cancer trial, the most common severe to life-threatening side effects that increased by 2 percent or more in people who received Avastin plus IFL chemotherapy vs. IFL alone were weakness (10 percent vs. 7 percent), abdominal pain (8 percent vs. 5 percent), pain (8 percent vs. 5 percent), high blood pressure (12 percent vs. 2 percent), blood clots in the veins of the body (9 percent vs. 5 percent), blood clots inside the abdomen (3 percent vs. 1 percent), a brief loss of consciousness (3 percent vs. 1 percent), diarrhea (34 percent vs. 25 percent), constipation (4 percent vs. 2 percent), reduced white blood cell counts (37 percent vs. 31 percent), and reduced white blood cell counts that may increase the chance of infection (21 percent vs. 14 percent).
Second-line Metastatic Colorectal Cancer: In the second-line metastatic colorectal cancer trial, the most common severe to life-threatening and fatal side effects that increased by 2 percent or more in people who received Avastin plus FOLFOX4 chemotherapy vs. FOLFOX4 alone were diarrhea (18 percent vs. 13 percent), nausea (12 percent vs. 5 percent), vomiting (11 percent vs. 4 percent), dehydration (10 percent vs. 5 percent), blockage of the bowel (4 percent vs. 1 percent), numbness and tingling in fingers and toes (17 percent vs. 9 percent), nervous system disturbances (5 percent vs. 3 percent), tiredness (19 percent vs. 13 percent), abdominal pain (8 percent vs. 5 percent), headache (3 percent vs. 0 percent), high blood pressure (9 percent vs. 2 percent), and severe bleeding (5 percent vs. 1 percent).
For full Prescribing Information and Boxed WARNINGS on Avastin please visit http://www.avastin.com.
Xeloda is indicated as a monotherapy to treat colorectal cancer that has spread (metastasized) to other parts of the body. Patients should know that in studies, other medicines showed improved survival when they were taken together with 5-FU and Leucovorin. In clinical studies of metastatic colorectal cancer, Xeloda monotherapy was no worse than 5-FU and Leucovorin taken together, but did not improve survival compared to these two medicines.
Xeloda Boxed WARNINGS and Additional Important Safety Information
Xeloda may increase the effect of blood thinning medicines, such as warfarin and other coumarin derivatives, and could lead to serious side effects if taken at the same time as these medicines. It is very important that doctors closely monitor patients who are taking blood thinning medicines and Xeloda, checking more often how quickly their patients’ blood clots and, if needed, changing the dose of the blood thinning medicine.
The most common side effects of Xeloda are: diarrhea, nausea, vomiting, sores in the mouth and throat (stomatitis), stomach area (abdominal) pain, upset stomach, constipation, loss of appetite, and too much water loss from the body (dehydration). These side effects are more common in patients age 80 and older. Other common side effects are hand-and-foot syndrome (tingling, numbness, pain, swelling or redness in the palms of the hands or soles of the feet); rash; dry, itchy or discolored skin; nail problems; hair loss; tiredness; weakness; dizziness; headache; fever; pain (including chest, back, joint and muscle pain); trouble sleeping; and taste problems. Patients should tell their doctor if they have heart problems because they could have more side effects related to their heart.
These side effects may differ when taking Xeloda with docetaxel. Patients should consult their doctor for possible side effects that may be caused by taking Xeloda with other therapies.
Women should not become pregnant while taking Xeloda and should not take Xeloda while nursing a baby.
For full Prescribing Information, including Boxed WARNINGS and Important Safety Information on Xeloda please visit http://www.xeloda.com.
Herceptin is approved for the adjuvant treatment of HER2-overexpressing, node-positive or node-negative (ER/PR-negative or with one high-risk feature) breast cancer. Herceptin can be used several different ways: as part of a treatment regimen including doxorubicin, cyclophosphamide, and either paclitaxel or docetaxel; with docetaxel and carboplatin; as a single agent following multi-modality anthracycline-based therapy.
Herceptin Boxed WARNINGS and Additional Important Safety Information
Herceptin treatment can result in heart problems, including those without symptoms (reduced heart function) and those with symptoms (congestive heart failure). Some patients have had serious infusion reactions and lung problems; fatal infusion reactions have been reported. Worsening of low white blood cell counts associated with chemotherapy has also occurred. Herceptin can cause low amniotic fluid levels and harm to the fetus when taken by a pregnant woman. The most common side effects associated with Herceptin were fever, nausea, vomiting, infusion reactions, diarrhea, infections, increased cough, headache, fatigue, shortness of breath, rash, low white and red blood cells, and muscle pain. Because everyone is different, it is not possible to predict what side effects any one person will have. Patients with questions or concerns about side effects should talk to their doctor.
For full Prescribing Information, including Boxed WARNINGS and Important Safety Information on Herceptin please visit http://www.herceptin.com.
Founded more than 30 years ago, Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes medicines to treat patients with serious or life-threatening medical conditions. The company, a wholly owned member of the Roche Group, has headquarters in South San Francisco, California. For additional information about the company, please visit http://www.gene.com.
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