“We acknowledge the overwhelming volume of cancer research, its rigors and challenges as we find the Philippines participating in more global clinical trials,” Dr. Maria Belen Tamayo, vice president of the Philippine Society of Medical Oncology (PSMO) said at this year’s PSMO Convention, held at Shangri-La last April. “We remain steadfast in our hopes for even more exciting and effective ways to treat cancer.”
Themed “Cancer Treatment… the best is yet to come,” the convention underscored every oncologist’s desire to provide the most effective treatment to his or her patients. It featured lectures by leading experts in the field and provided local oncologists a glimpse of the exciting advances in cancer treatment.
Tykerb in metastatic breast cancer
Dr. Frances M. Boyle, chairman of the Department of Cancer Medicine at the Mater Private Hospital in North Sydney, Australia, set the tone for the lectures on these new developments. Aiming “to give flavors on how treatments are made,” she tackled the role of lapatinib (Tykerb) in treating metastatic breast cancer in patients whose tumors overexpress HER2 and who have received previous treatment with an anthracycline, a taxane, and trastuzumab.
Tykerb is given orally in combination with capecitabine (Xeloda) for the treatment of patients with advanced or metastatic breast cancer. The combination of both oral agents is an attractive option that does away with hospitalization for parenteral (non-oral) drugs. The recommended dose of Tykerb is 1,250 mg (five tablets) given orally once daily on days 1-21 continuously in combination with capecitabine at 2,000 mg/m2/day (administered orally in two doses approximately 12 hours apart) on days 1-14 in a repeating 21-day cycle. Data from the large clinical trial that was testing Tykerb in combination with Xeloda versus Xeloda alone showed that the patients who received the combination had more time before their cancer progressed than patients who received Xeloda alone.
Avastin in breast cancer
Dr. Mark Farrell Kozloff, currently the medical director of Oncology and the program chairman of the Comprehensive Cancer Program at Ingalls Health System in the United States, delivered the second lecture on the novel treatment of breast cancer.
Avastin, in combination with intravenous 5-fluorouracil-based chemotherapy, was first approved for first- or second-line treatment of patients with metastatic carcinoma of the colon or rectum. Subsequently in combination with carboplatin and paclitaxel, Avastin was indicated for first-line treatment of patients with unresectable, locally advanced, recurrent or metastatic nonsquamous, nonsmall-cell lung cancer.
A total of 722 women with recurrent or metastatic breast cancer who had not previously received systemic chemotherapy for their recurrent or metastatic disease were enrolled in this study between December 2001 and May 2004. Patients in the study who received bevacizumab in combination with standard chemotherapy consisting of single-agent paclitaxel had a delay in worsening of their cancer by approximately five months on average compared to patients treated with paclitaxel chemotherapy alone, a statistically significant difference. The results include the facts that those on bevacizumab plus standard chemotherapy had progression-free survival of 10.97 months vs. 6.11 months on standard chemotherapy alone—a 49 percent improvement in progression-free survival. There was a 28 percent response rate for those on bevacizumab plus standard chemotherapy vs. 14 percent for those on standard chemotherapy only.
The benefits of this novel treatment that Dr. Kozloff enumerated include substantial prolongation of life, higher quality of life (QOL), superior one-year survival, and positive risk-benefit ratio.
An animated open forum concluded Dr. Kozloff’s lecture. Dr. Valorie Fullon-Chan, medical-oncology consultant at the Philippine General Hospital, Veterans Memorial Hospital, and several large teaching institutions in the metropolis, raised the issue of the high cost of cancer treatment in the country. Could the dose be lowered and yet achieve the same response as the recommended dose? How can the cost of anticancer drugs be lowered?
Beyond clinical practice, Dr. Kozloff remarked that there were “societal problems that we need to solve.” But he cautioned his audience about giving the drugs at a dose outside the usual recommendations. He advised them to consider the patients’ preferences regarding the treatment they wish to undergo, although as part of his routine practice he makes it a point to “offer the patient the best treatment available.”
Dr. Kozloff is a member of various professional organizations including Cancer and Leukemia Group B, Southwest Oncology Group, American Society of Clinical Oncology, American Society of Hematology, Eastern Cooperative Study Group, National Comprehensive Cancer Network, and European Society of Medical Oncology.
Avastin is marketed in the Philippines by Roche.
Erbitux in colorectal cancer
The third lecture highlighted the options and challenges in the treatment of colorectal cancer, the fourth commonest malignancy worldwide. In the Philippines, cancers of the colon and rectum ranked third overall, third among males and fourth among females. In 2005, over 6,000 patients died of the disease even as over 14,000 new cases were diagnosed.
“In Europe, there are 376,400 new cases annually,” Dr. Carsten Bokemeyer reported in his lecture, “and over 203,700 deaths annually, 25 percent of which from metastatic disease.” He is currently the director of the University of Oncology and Hematology at the University Hospital Hamburg-Ependorff, Hamburg, Germany.
Dr. Bokemeyer focused on the role of cetuximab (Erbitux) as a treatment option for patients who have colorectal cancer that has spread to other parts of the body and whose tumor expresses a protein called an epidermal growth factor receptor (EGFR). EGFR is overexpressed in 50 percent to 70 percent of human primary carcinomas of breast, lung, and colon. Activation of this receptor has been proposed to be involved in the aggressive growth and spread of colorectal cancer.
The body produces agents that signal both normal and cancer cells to grow and divide. Both normal and cancer cells have structures called receptors sticking out from the cell surface. When a signaling agent binds to a receptor, it makes things happen within the cell. By binding to EGFR on the surface of both normal and tumor cells, Erbitux can block the receptor from binding to signaling agents that would otherwise cause the cell to grow and divide. When this happens to cancer cells, these cells may stop growing and dividing, causing the tumor to shrink.
Dr. Bokemeyer presented data from a study on patients with EGFR-expressing, previously treated, recurrent, metastatic colorectal cancer. Patients were randomized (1:1) to receive either Erbitux plus best supportive care (BSC) or BSC alone. Erbitux was administered as a 400-mg/m2 initial dose, followed by 250 mg/m2 weekly until disease progression or unacceptable toxicity. Higher median survival was noted among those who received Erbitux (6.14 mos. vs. 4.57 mos.). Several studies have also shown increased response rates and increased progression-free survival with Erbitux.
“Can we improve on that number?” asked Dr. Bokemeyer. While the tumor response rates for patients with nonresectable liver metastasis with the usual regimens are in the 50 percent to 60 percent range, the combination of Erbitux and FOLFOX4 has improved response to 72 percent. He also drew attention to the three-fold increase in the rates of resection with clear margins in patients with initially nonresectable tumors after combination therapy involving Erbitux.
Dr. Bokemeyer, who has published more than 100 book chapters, over 200 original publications and more than 50 peer-reviewed articles in medical oncology, also stressed the routine multidisciplinary team approach in the management of colorectal cancer, citing the European Colorectal Cancer Treatment Group recommendation that “no patient should be operated on without a multidisciplinary team meeting.”
He ended his lecture by mentioning an ongoing study on the use of Erbitux in the adjuvant setting.
Erbitux is marketed in the Philippines by Merck Inc.
Durogesic in optimal pain management
The fourth lecture in the series veered away from the utility of targeted therapy in the management of solid tumors, but addressed one important concern in cancer treatment, especially in the metastatic setting: pain control.
Philippine-born and trained, Dr. Bernard R. Canlas is currently the continuing medical education (CME) director and pain-management specialist of the Institute of Pain Management in Jacksonville, Florida. He took to the floor during his lecture quoting Patrick Wall, “Untreated cancer pain accelerates death.” Citing American Cancer Society data, he estimated that by 2020, there will be 16 million Americans with cancer yearly, cancer-related death will have declined by 1.8 percent, and over six million will become cancer survivors. The downside of the data, however, is that 50 percent of survivors especially among those with breast cancer will suffer from chronic pain.
Dr. Canlas first discussed the many mechanisms of pain in cancer and provided examples of the various treatment options available on the market today. He stressed the need for adequate pain control among cancer patients because “existential consequences of unrelieved cancer pain have been reported.” He focused his lecture on Durogesic (fentanyl), a transdermal system providing continuous systemic delivery of fentanyl, a potent opioid analgesic, for 72 hours. Durogesic belongs to the family of opioids, a group of very strong painkillers related to morphine. They work by mimicking the action of naturally occurring pain-reducing chemicals called endorphins. Endorphins are found in the brain and spinal cord and reduce pain by combining with opioid receptors.
Fentanyl mimics the action of natural endorphins by combining with the opioid receptors in the brain and spinal cord. This blocks the transmission of pain signals sent by the nerves to the brain. Therefore, even though the cause of the pain may remain, less pain is actually felt.
The World Health Organization, as well as the other pain specialist organizations worldwide, recommends morphine as the opioid of first choice for cancer-pain relief. A proportion of patients develop intolerable adverse effects with morphine before achieving pain relief, and a change to an alternative opioid or a change of the route of administration is deemed appropriate. In one study presented by Dr. Canlas comparing fentanyl with morphine, those in the fentanyl group experienced fewer side effects and rated their pain treatment more effective than those on long-acting morphine.
Dr. Canlas, who has been involved in various clinical trials and has published several articles in peer-reviewed journals, also discussed the potential for abuse of opioids among patients and even among nonpatients. He cited studies that the transdermal route (particularly Durogesic) has the least potential for addiction, with the intravenous and inhalational routes having the highest risks for dependence. According to Dr. Canlas, Durogesic has the lowest street value among drug abusers in the United States because its unique matrix system releases fentanyl from the reservoir at a nearly constant rate, thus preventing opportunity for abuse.
Dr. Canlas is a member of various professional organizations including the International Society of Spinal Endoscopists, the American Society of Regional Anesthesia and Medicine, the American Society of Interventional Pain Physicians, the Philippine Society of Anesthesiologists, and the Pain Society of the Philippines, and has been named one of America’s Top Anesthesiologists for 2007. He is also a founding member of the Department of Anesthesiology at the Asian Hospital and Medical Center.
Durogesic is marketed in the country by Janssen.
“…the best is yet to come”
PSMO president Dr. Noemi Alsay-Uy: Science and pragmatism must come together in the final choice of treatment options
PSMO president Dr. Noemi Alsay-Uy proudly considered the convention a forum to “provide [medical oncologists] opportunities for exploring and learning a broad range of innovative therapies,” even echoing Dr. Boyle’s views in her lecture that “when weighing things up in the management of cancer, science and pragmatism play [a] central role in the final choice among the treatment options.” 