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October 30, 2006
Rather than submit to more chemotherapy, a Pennsylvania woman whose ovarian cancer was in remission opted for a new treatment method. Vaccinations are a routine part of many people’s lives from the time they are small children. Before going to school, immunizations against ailments such as measles, mumps, rubella, and chickenpox are standard for youngsters. As adults, some people receive vaccinations against tetanus, the flu, or even common allergens. Ongoing trials, though, may add vaccines for cancer to that list. For Christine Sable, a clinical trial for an ovarian cancer vaccine may have spared her from a relapse of the potentially fatal disease, though whether the vaccine is ready for mass marketing remains undetermined. Backstory Additionally, she says she often woke up with lower back pain, couldn’t lose weight despite a regular exercise routine, sometimes felt bloated, was more fatigued than usual, and had more headaches. “But none of these symptoms were severe or anything that would normally send me running to the doctor,” she says. “What made me finally go to see a doctor were the persistent cramps and the urinary frequency.” The result of that doctor’s visit? “I went in to my family practitioner on a Thursday and by the following Thursday, I was having surgery for advanced ovarian cancer,” Sable recalls. Concerned about Sable’s symptoms, her physician had ordered ultrasounds—abdominal and transvaginal—for the day after Sable’s appointment. “After these procedures were done, the ultrasound technicians would not share any results and, because they had spent so much time trying to get pictures of the ovaries, I felt sure something was seriously wrong,” she says. “By the time I got home from outpatient testing, my phone was ringing. It was the doctor’s nurse telling me that they had found something suspicious on the ultrasound and [the doctor] wanted me to go back in that afternoon for a CT [computed tomography] scan. “When I asked what the report said, [the doctor’s nurse] told me that it showed complex masses on both ovaries,” Sable says. “That answer went through me like a knife. I asked how large the masses were and she told me about the size of grapefruits. From that moment on, I knew I had ovarian cancer.” In addition to the CT scan, her doctor ordered a test for CA (cancer antigen) 125, a blood protein that is sometimes elevated in patients diagnosed with ovarian cancer. While waiting for the results, Sable began searching the Internet for information about her situation. “To my horror, every symptom I had was on the list,” she says. “So I kind of figured out exactly what was going on before I went back in Monday to get the test results from my family doctor.” The results of Sable’s test showed significant tumors on both ovaries and throughout her abdominal region; her CA 125 levels were elevated as well. “Everyone asks me if I ever had any prior health problems and if there was any history in my family of cancer,” Sable says. “This cancer completely showed up out of nowhere and there was no family history, environmental exposure, or other health reason to explain it. I had been healthy all my life with no serious illnesses and I did not smoke or take any undue risk with my health. In fact, I had a number of factors that would normally lower my risk.” Linda Van Le, MD, a professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill, says women usually aren’t aware of the development of ovarian cancer until the disease has reached an advanced stage. Common symptoms, such as an enlarging abdomen and gastrointestinal symptoms often attributed to indigestion, may be vague until women become more fatigued or unable to eat, “at which point, there’s usually a lot of cancer,” says Van Le. “Mortality is anywhere from 30% to 50% at five years,” adds Van Le. Treatment Following her surgery, Sable had six rounds of chemotherapy. “I went through the usual nausea, fatigue, bone pain, and balding from the chemotherapy,” she says. “In October 2003, I finished my last chemo and was declared in remission based on a clear CT scan and a very low CA 125 test. “At that time, I was offered additional rounds of chemo called consolidation therapy—extra chemo cycles that were supposed to help make the remission stick,” Sable says. “I turned it down, feeling that my immune system had already been so weakened and now that I was in remission, I needed to build up that immune system as much as possible. So no more chemo for me, I decided.” A Glimmer of Hope “Knowing how poor my chances were of living even five years, I set to work researching all kinds of clinical trials on the Internet and through other resources. But most of the trials were just more forms of chemo and I didn’t want that,” says Sable. Then, while watching the evening TV news, Sable learned of a vaccine trial at Roswell Park Cancer Institute (RPCI) in Buffalo, N.Y. She discovered the trial in question was for a vaccine involving the NY-ESO-1 antigen. “NY-ESO-1 is the most immunogenic cancer antigen to date,” says Kunle Odunsi, MD, PhD, associate professor and research program director in the department of gynecologic oncology at RPCI. “NY-ESO-1 is not expressed by normal tissues except adult testis, but it is expressed by a variety of cancers. Based on work at RPCI, we have determined that the NY-ESO-1 antigen is expressed in a significant number of ovarian cancer patients.” The trial involving NY-ESO-1 is part of the Cancer Vaccine Collaborative (CVC), a partnership between the Ludwig Institute for Cancer Research (LICR) and the Cancer Research Institute (CRI). “The purpose of the collaborative is to conduct single variable, multi-institutional, parallel clinical investigations to discover the best way to generate effective antitumor immunity in humans,” explains Odunsi. “While it is clear that cancers utilize several mechanisms to escape immune attack, there has been no systematic effort to address the issues affecting the ability to generate antitumor response.” Initially limited to New York City, the collaborative has been expanded to institutions in other countries, including the United Kingdom, Germany, Switzerland, Japan, and Australia. RPCI became a site for the CVC in 2002 and is the major site for the ovarian cancer vaccine program. Scientific expertise, reagents, and administrative/regulatory oversight for the collaborative are provided by the LICR and funding for personnel and reagents by the CRI. “The goal of the NY-ESO-1 vaccination in ovarian cancer is to prevent the relapse of the disease by immunizing patients who have completed their treatment and have no evidence of the disease,” says Odunsi. “In this way, the immune system is taught to be ready to attack and kill cancer cells if and when they start to relapse.” When Sable found out about the trial at RPCI, the program was recruiting for phase 1 patients, of which there would be only 18. Sable fulfilled the requirements for entering the trial, which included having completed chemotherapy, being in clinical remission, and having a clear CT scan. She started the trial in February 2004, with five shots initially planned for her treatment. “I ended up getting a total of 20 shots because I exhibited a very strong immune response to the vaccine and continued to stay in clinical remission,” says Sable. Odunsi, the trial physician, explains that vaccines can be made in several different ways. “A short fragment [peptide] or the full-length NY-ESO-1 protein can be administered with adjuvants [immune boosters],” he says. “We have also inserted NY-ESO-1 into viruses so that the immune system is tricked into reacting against the virus. In the process, it also reacts against the NY-ESO-1 antigen.” There are numerous challenges to such testing in humans, according to Odunsi. Those challenges include the ability to make a reagent that is safe for humans and to obtain adequate funding and support to conduct laboratory investigations to accompany the testing. “Therefore, without the CVC, it will be impossible to assemble a critical mass of investigators that are committed to advancing the field and potentially bring benefits to cancer patients,” he says. Those women who were eligible to participate in the clinical trial at RPCI had tumors that expressed the NY-ESO-1 antigen. The goals for the trial in which Sable participated are prolonging the time in which a relapse of the cancer might occur and inducing effective antitumor immune response, says Odunsi. The trial at RPCI is limited to ovarian cancer patients at this point, but there are ongoing CVC trials for patients with other types of cancers such as melanoma, prostate, bladder, and sarcomas. Getting the shots required Sable to go to Buffalo once every three weeks for three days at a time. Following a physical exam, Sable would receive a shot on the outside muscle of her arm on the first day of each visit. She would return two days later so a nurse could examine the injection site for redness, swelling, or a rash, something Sable never experienced. “I felt normal and could do all my normal activities. I had no side effects other than a little soreness at the injection site, much like getting a flu shot,” Sable says. Sable says the only downside of her participation in the clinical trial was the traveling and time spent away from her family. Her visits to RPCI required a two-hour drive to the airport in the Baltimore-Washington, D.C., area followed by the flight. She frequently went to Buffalo alone to keep down the cost of lodging and traveling. Sable made a total of 24 trips to Buffalo, finishing her treatment in March 2005. Current Results Odunsi says it is too soon to determine, though, whether the NY-ESO-1 can be marketed the way the recently released cervical cancer vaccine Gardasil has been. “I feel extremely fortunate to have participated in this trial,” says Sable. “While the results are not completely in yet, I feel very strongly that the vaccine has a great deal to do with the fact that I am still alive, healthy, and in remission today.” She adds that her CA 125 level was recently tested and remains low, “a good sign that my immune system is keeping the cancer in check. I feel as if I have been given another chance at life and that gives me a tremendous sense of joy, hope, and gratitude.” — Tracy Meadowcroft is an editorial assistant
at For The Record.
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