THURSDAY, Sept. 24, 2009 (HealthDay News) -- An experimental treatment for advanced melanoma promotes rapid shrinking of tumors, according to a new study.
The phase I extension trial includes patients with the cancer-causing mutation of the BRAF gene, which is associated with about 50 percent of melanomas and 5 percent of colorectal cancers.
The patients were given 960 milligrams of PLX4032 twice a day. Of the 22 patients evaluated to date, 14 (64 percent) showed at least 30 percent shrinkage in the diameter of tumors for at least a month -- the official criteria for partial response to the treatment. Another six of the 22 patients also showed a response, but it was too early to determine whether the tumors would shrink enough to meet the criteria for partial response.
The findings were scheduled to be presented Thursday in Berlin at a meeting of the European Cancer Organization and the European Society for Medical Oncology.
"We are very excited about these results. Of the 22 patients we have been able to evaluate so far, 20 have had some objective tumor shrinkage. This is impressive as they all had metastatic disease, and most of them had failed several prior therapies," trial co-leader Dr. Paul Chapman, an attending physician on the melanoma/sarcoma service at Memorial Sloan-Kettering Cancer Center in New York City, said at a news briefing.
"A lot of these patients were pretty sick, but many of them had a significant and rapid improvement in the way they function. We've had patients come off oxygen, and we've got several patients who have been able to come off narcotic pain medication soon after starting treatment," Chapman said.
"What makes this treatment different from standard chemotherapy is that standard chemotherapy attacks the machinery involved in cell division; so to stop the cancer cells dividing uncontrollably, most standard chemotherapy aims to block the mechanism of division by interfering directly with DNA replication or with microtubules in the dividing cells," he explained.
"PLX4032 is different because it attacks the genetic program that is causing the cells to divide uncontrollably, and we think the BRAF mutation is driving that program. The drug is blocking the genetics of the tumor, rather than trying to interfere with the proliferation of the cells and, as a result, there are fewer side effects, although there are some. We are seeing some pretty dramatic and rapid responses, and they are occurring in sites where we rarely see responses to chemotherapy, such as in the bone."
Chapman noted that "we don't know yet how long these responses will last, and we have had patients whose cancer has progressed after initially responding; so we are putting a lot of effort into studying the patients who do relapse, trying to understand how their tumors have become resistant.
"In addition, one of the main side effects we've seen is that some patients develop early, non-melanoma skin cancers, such as squamous cell skin cancer. We are very vigilant about this, and although they are very easy to cut out, it's something we are keeping a close eye on."
A phase II trial involving 90 patients will start at the end of this year, and a phase III trial involving several hundred patients is scheduled to begin at the end of this year or early next year.
In related news from the cancer meeting in Berlin, researchers said they've shown that ultrasound can be used to identify whether cancer has started to spread in melanoma patients, and to what extent. This information can help doctors decide how much surgery, if any, a patient requires and predict the patient's likelihood of survival.
"We have identified two ultrasound patterns of lymph node metastasis in melanoma patients which can identify correctly any amount of tumor cells in the sentinel lymph nodes in 75 to 90 percent of cases before proceeding to surgery on the sentinel lymph nodes," Dr. Christiane Voit, head of the diagnostic unit at the Skin Cancer Center at the Medical University of Berlin, said in a news release prepared before the meeting.
Since 2001, she and her colleagues have tested the use of ultrasound in diagnosis and treatment planning of 850 melanoma patients. The research findings need to be confirmed in multi-center, randomized trials, Voit said.
The U.S. National Cancer Institute has more about melanoma.