The FDA and Ligard Pharmaceuticals notified health professionals and consumers of [label changes for Avinza™](http://www.fda.gov/medwatch/safety/2005/safety05.htm#Avinza) on November 3, 2005. Avinza™ is an extended release form of morphine sulfate provided in capsules. Alcohol can cause a potentially fatal overdose of the drug. FDA MedWatch said,

“Ligand Pharmaceuticals Inc. and FDA notified healthcare professionals of revisions to BOXED WARNING, WARNINGS, PRECAUTIONS, CLINICAL PHARMACOLOGY, and DOSAGE AND ADMINISTRATION sections of the prescribing information to highlight and strengthen the warning that patients should not consume alcohol while taking Avinza. Additionally, patients must not use prescription or non-prescription medications containing alcohol while on Avinza therapy.

Ligard Pharmaceuticals, manufactures of Avinza™ issued a [Dear Health Professional Letter](http://www.fda.gov/medwatch/safety/2005/Avinza-ltr.pdf) to let them know of changes in the labeling. Included in that letter was the following addition to the *Black Box Warning* on the Avinza™ label.

Patients must not consume alcoholic beverages while on AVINZA therapy.
Additionally, patients must not use prescription or non-prescription medications
containing alcohol while on AVINZA therapy. Consumption of alcohol while taking
AVINZA may result in the rapid release and absorption of a potentially fatal dose of morphine.

The [new Avinza label](http://www.fda.gov/medwatch/safety/2005/avinza_PI.pdf) with changes highlighted in yellow can be downloaded as a PDF.

[Edward A. Levine M.D.](http://www1.wfubmc.edu/gs/about/faculty/DrLevine.htm), professor of surgical oncology at Wake Forest Baptist Medical Center, will perform surgery with intraperitoneal hyperthermic chemotherapy and discuss the treatment of cancer that has spread into the abdominal cavity during a [free webcast on November 17](http://www.or-live.com/WFUBMC/1478/)

**Webcast**

+ Intraperitoneal Hyperthermic Chemotherapy for Persistant Cancer
+ November 17, 2005
+ 5 p.m. (Eastern Time)
+ [Connection information](http://www.or-live.com/WFUBMC/1478/)

Cancer that spreads from the colon into the abdominal (*peritoneal*) cavity is particularly difficult to treat. Tumors develop on the peritoneum itself and on the surfaces of abdominal organs. Cancer cells may circulate in the fluid inside the abdominal cavity.

Wake Forest, among other specialized surgical centers, has developed treatment that combines surgery to remove as much visible cancer as possible (*cytoreduction*) with pumping heated chemotherapy into the abdomen (*intraperitoneal hyperthermic chemotherapy or IPHC*). The technique has been successful in achieving long-term remissions for a percentage of carefully chosen patients.

[Science Daily](http://www.sciencedaily.com/releases/2004/02/040212085309.htm) reported on publication of Wake Forest research to treat peritoneal cancer in February, 2004.

Research results of the work of Dr. Levine, Dr. Perry Shen, and their colleagues at Wake Forest Baptist Medical Center were published in the [*Annals of of Surgical Oncology*](http://www.annalssurgicaloncology.org/cgi/content/abstract/11/2/178) in 2004 — *Cytoreductive Surgery and Intraperitoneal Hyperthermic Chemotherapy With Mitomycin C for Peritoneal Carcinomatosis from Nonappendiceal Colorectal Carcinoma.*

*Information from the 2005 American College of Gastroenterology Scientific Meeting*

Diabetics are 40% more likely than people without diabetes to develop colorectal cancer according to a [study reported on Monday](http://www.acg.gi.org/media/releases/ACG05Release_DiabetesRiskforCRC.pdf) at the [Annual Scientific Meeting](http://www.acg.gi.org/physicians/meetings/annualmtg/05meeting/program.asp#scientific) of the American College of Gastroenterology in Honolulu.

Researchers from Medical University of South Carolina in Charleston analyzed information from nearly 227,000 responses to the [National Health Information Survey](http://www.cdc.gov/nchs/nhis.htm) from 1997-2003. About 6% of people in those studies had diabetes.

After adjusting for other factors that influence the development of colorectal cancer including age, gender, race, obesity, alcohol and tobacco use, and physical activity the researchers concluded that people with diabetes have a risk of colorectal cancer 1.4 times those without the disease.

In an interview with [Reuter's Health](http://today.reuters.co.uk/news/newsArticle.aspx?type=healthNews&storyID=2005-11-03T003801Z_01_KRA302240_RTRIDST_0_HEALTH-DIABETICS-CANCER-DC.XML&archived=False) Dr. Donald Garrow from the research team explained that receptors for insulin are present on colon tissue and that is is possible that high levels of insulin create changes in colon cells that lead to colorectal cancer. He also told Reuters that cell culture studies suggest high blood sugar levels promote colorectal cancer growth.

Garrow said that the team is now evaluating whether or not diabetics need to begin colorectal cancer screening earlier than those at average risk and whether controlling blood glucose can make a difference in the development of colorectal cancer.

Read more articles about the study report on [*Medpage Today*](http://www.medpagetoday.com/Gastroenterology/ColonCancer/tb1/2052) and [Forbes.com](http://www.forbes.com/health/feeds/hscout/2005/11/01/hscout528835.html).

**Panitumumab** is a biologic agent with the potential to block *epidermal growth factor receptors (EGFr)* and reduce progression of colorectal cancer. Clinical trials of panitumumab, both alone and in combination with chemotherapy, have been closely watched by patients with colorectal cancer, some of whom are part of those trials.

This morning, November 3, 2005, a press release from [Amgen and Avgenix, Inc. announced](http://www.amgen.com/media/media_pr_detail.jsp?releaseID=777851) that clinical trials appeared to show that **panitumumab**, given alone, significantly improved progression-free survival time for patients with metastatic colorectal cancer. Patients in the trial had cancer that had spread beyond their colons (*metastasis*) and had already had their disease get worse on standard chemotherapy (*refractory*).

*Study Design* In the Phase III trial over 460 patients were randomized to receive either intravenous panitumumab every two weeks along with best supportive care or best supportive care alone. Supportive care included pain medications, radiation or surgery to relieve pain, blood transfusions, or other treatment designed to relieve symptoms. It did not include chemotherapy.

All patients in the study had previously been treated with both oxaliplatin (Eloxotin™) and irinotecan (Camptosar™) along with fluorouracil (5-FU) and had progressed on those treatments.

*Study results* Patients who received panitumumab had a 46% lower rate of tumor progression than those in the best supportive care arm, exceeding the trial design goal of at least a 33% lower progression-free survival rate. A secondary goal for objective response to the drug –reduction in tumor size –was also met. Overall survival will be analyzed in the future — 12 months after the time the last patient entered the study.

*Side effects* Despite the fact that no pre-medication was used to prevent them, reactions to the panitumumab infusion were limited and not severe. The most common side effect was an acne-like rash. Other less common side effects included fatigue, nausea, and mild diarrhea. The reseacher team did not find any formation of *human antihuman antibody (HAHA)* or anti-panitumumab antibodies.

*Panitumumab* (previously called ABX-EGF) is a fully-humanized monoclonal antibody that targets the *epidermal growth factor receptor (EGFr)*, blocking its activity. EGFr contributes to the growth of several cancers, including colorectal cancer. The fully-humanized agent eliminates mouse proteins present in other EGFr targeted therapies, hopefully reducing allergic reactions during its infusion into the body.

Previous Phase II results were presented as an [abstract](http://asco.org/ac/1,1003,_12-002643-00_18-0034-00_19-0030047,00.asp) at the 2005 annual meeting of the American Society of Clinical Oncology in Orlando.

Panitumumab is currently being evaluated in [clinical trials](http://www.amgentrials.com/general/search_results.htm?ExpressionSpec=panitumumab&search.x=0&search.y=0) both as a single agent (monotherapy) and in combination with chemotherapy in several clinical trials for colorectal and other cancers. Among them, the Phase III PACCE trial randomizes patients with newly diagnosed metastatic colorectal cancer to chemotherapy alone or chemotherapy with panitumumab.

Willard Dere, M.D., chief medical officer and senior vice president of Global Development at Amgen said in the [news release](http://www.amgen.com/media/media_pr_detail.jsp?releaseID=777851) of the clinical trial results,

Amgen is dedicated to developing safe and effective cancer therapies that significantly improve cancer patients’ outcomes, We are excited that panitumumab, our most advanced investigational cancer therapeutic, improved progression-free survival and response rate in metastatic colorectal cancer patients who had failed multiple prior chemotherapy regimens. These results will support a BLA submission, which we plan to initiate by the end of the year.

Should the presence of iron deficiency anemia be part of the decision-making as to whether to examine the entire colon when patients have symptoms of colorectal cancer?

Researchers reviewed hemoglobin levels for 194 patients who had surgery for colon cancer in right-hand or ascending portion of the colon (*right hemicolectomy*). 44% of men and 57% of women met definitions for anemia. Even when less a stringent definition of “low hemoglobin” were used, not all patients were found to be anemic.

It is not possible to rule out right-sided colon cancer if symptomatic patients are not anemic, and a full examination of the colon with colonoscopy is essential when patients have symptoms of colorectal cancer. At the same time, unexplained anemia may be a sign of right-sided colon cancer and should also be evaluated with colonoscopy.

Study results appear in the November 2005 issue of [Colorectal Disease](http://www.ingentaconnect.com/content/bsc/cdi/2005/00000007/00000006/art00010) The authors concluded,

Anaemia is a poor predictor of right-sided colon cancers and cannot be used as an effective investigative tool in symptomatic patients.