By Elizabeth Whittington

Tarceva Extends Survival Time in Pancreatic Cancer

Pancreatic cancer is a disease that has proven hard to treat and harder to cure. In the past, surgery has been the only curative option for patients, but the risk of recurrence was still high, even after complete removal of the pancreas. In 1996, Gemzar® (gemcitabine) was approved for inoperable pancreatic cancer and has become the standard chemotherapy treatment. Since then, several drugs, including Alimta® (pemetrexed) and Eloxatin™ (oxaliplatin), have been combined with Gemzar but have failed to prolong survival in pancreatic cancer.

Finally, some hopeful news was presented at the ASCO Gastrointestinal Cancers Symposium in January 2005, where promising results of a phase III trial combining Tarceva™ (erlotinib), an oral pill that blocks epidermal growth factor receptor (EGFR), with Gemzar were announced. The trial included 569 patients with advanced pancreatic cancer. Patients receiving Tarceva with Gemzar experienced an improvement in overall survival (6.37 months versus 5.91 months) compared with patients taking Gemzar alone. More encouragingly, after one year of therapy, 24 percent of patients receiving Tarceva and Gemzar were alive compared with 17 percent who were taking only Gemzar.

Tarceva is a small-molecule inhibitor of EGFR, a small protein found on the cell’s surface. Pancreatic cancer frequently overexpresses EGFR, which can be a sign of more aggressive disease and poorer prognosis. Overstimulation of EGFR is frequently seen in pancreatic cancer. Tarceva is the first drug to show a survival improvement in this type of disease with side effects that included rash and diarrhea. For more on Tarceva, visit www.tarceva.com.

A One-Two Punch Against Advanced Colorectal Cancer

Two weapons against colon cancer include Erbitux™ (cetuximab), which targets a protein called EGFR that is found on most colon cancer cells, and Avastin™ (bevacizumab), which helps prevent the formation of new blood vessels for tumor growth. Oftentimes, researchers will combine two or more drugs that are proven to work by themselves to see if the combination is even more powerful.

The BOND 2 study, conducted by Leonard Saltz, MD, and colleagues at Memorial Sloan-Kettering Cancer Center, combined Erbitux and Avastin in 35 patients with advanced colon cancer whose disease had progressed on chemotherapy agents like Camptosar® (irinotecan) and Eloxatin® (oxaliplatin). Twenty-three percent of patients had their tumors shrink by at least 50 percent using the combination, and the disease stayed in remission an average of 6.9 months in patients who responded. These results were significantly better than those seen with Erbitux alone, which resulted in 50 percent tumor shrinkage in only about 10 percent of patients.

Thirty-nine patients were given a three-drug combination of Avastin, Erbitux and Camptosar. With the addition of Camptosar, 38 percent of patients had their tumors shrink by at least half. The median time to progression (amount of time before the tumor grows in size) was extended to 8.5 months compared with 6.9 months with Avastin and Erbitux alone. Phase III studies are needed to determine if the three-drug combination can prolong survival. Toxicities included diarrhea, fatigue and rash.

For more information on these drugs, visit www.erbitux.com, www.avastin.com or www.camptosar.com. To see what other drug combinations are being studied in colon cancer, go to www.clinicaltrials.gov.

Approval of Prialt Opens New Door for Pain Relief

Nearly half of all patients undergoing treatment for cancer report experiencing pain, and for those with advanced cancer, the number rises to as many as 90 percent. When patients begin having chronic pain, which is defined as pain lasting longer than three to six months, quality of life begins to deteriorate. While there are several strong pain relievers such as morphine that are widely used, many cancer patients do not get adequate pain relief from even high doses of morphine (which can also cause drowsiness and constipation).
Direct administration of painkillers directly into the spinal fluid (intrathecal therapy) can allow patients with severe pain to get significant relief without some of the side effects seen with oral agents. Patients with cancer pain that does not respond to opioids, such as morphine, may now have another alternative.

The Food and Drug Administration (FDA) recently approved the use of Prialt® (ziconotide) after a phase III trial showed an improvement in pain relief in patients with severe pain. Based on the poisonous venom found in a small marine snail, Conus magus, Prialt works by targeting and blocking the calcium channels found on nerves that transmit pain signals. It was first developed in the mid-1990s, but the FDA had the drug tested in several trials before approving it this past December for patients with opioid-resistant chronic pain.

The phase III trial was conducted with 220 patients with opioid-resistant, severe chronic pain. Side effects were mild to moderate and included dizziness and headache. Some patients had confusion and other neurological side effects.
Prialt is 100 times more potent than morphine and has shown no signs of being addictive, a common fear for patients taking high or frequent doses of opioids. Prialt needs to be given by pain specialists and anesthesiologists who are expert in implanting spinal pumps and familiar with these medications.

For more information on Prialt, go to www.prialt.com.

Provenge Clears Another Hurdle Against Prostate Cancer

The completion of a successful phase III trial puts Provenge® vaccine (APC8015) one step closer to FDA approval for metastatic hormone-refractory prostate cancer (HRPC), a stage of the disease where it spreads beyond the prostate gland.

The trial results, announced at the 2005 ASCO Multidisciplinary Prostate Cancer Symposium held in Orlando in February, showed that Provenge extended survival by 4.5 months in patients who received the vaccine compared with placebo (25.9 months versus 21.4 months). After three years, patients taking Provenge were three times more likely to be alive than patients not taking the vaccine (34 percent compared with 11 percent). The most common side effect was temporary flu-like symptoms.

The data with Provenge vaccine has been somewhat conflicting, and a second phase III trial, which is expected to conclude this year, will hopefully confirm that the vaccine prolongs survival and delays tumor growth and pain associated with the disease.

Cancer vaccines use the body’s own immune system to attack cancer cells. Provenge specifically works by telling the body’s immune system to attack cells that express prostatic acid phosphatase, a protein found on 95 percent of prostate cancer cells.

For more information on Provenge, go to www.dendreon.com/dndn/provenge. For more information on clinical trials with vaccines, visit www.clinicaltrials.gov.