Combination Therapy Appears to Double Liver Cancer Survival
Adding photodynamic therapy to stents can improve survival in patients with unresectable cholangiocarcinoma, a new study shows. Reporting in the March issue of Clinical Gastroenterology and Hepatology, investigators showed that combination therapy improved survival from just over 7 months to more than 16 months.
Considered experimental in the United States, the therapy is already in use in Europe. The US Food and Drug Administration (FDA) has been reluctant to move forward without additional data.
The authors of this new study suggest that these findings will encourage a larger trial that explores the safety and efficacy of photodynamic therapy with stenting.
Lead author Michel Kahaleh, MD, from the University of Virginia Health System in Charlottesville, told Medscape Oncology that patients have been receiving off-label treatment at his center for some time and have been living longer as a result.
Dr. Kahaleh said that the treatment is the standard of care in Germany, a country that is ahead of all others when it comes to carcinoma and laser treatments. Dr. Kahaleh said he would like to see similar progress in the United States.
Cholangiocarcinoma Difficult to Treat
Cholangiocarcinoma is the second most common malignancy in the liver. The majority of patients are found to be unresectable on presentation; survival is approximately 3 months without intervention and 4 to 6 months with biliary decompression.
Photodynamic therapy is an ablative treatment. Specialists administer a photosensitizing drug, which is followed by a wavelength of light. This promotes intracellular activation of the drug and cellular injury.
Thrombosis of vessels and immune response can lead to the destruction of the tumor.
In an accompanying editorial, Todd Baron, MD, from the Mayo Clinic in Rochester, Minnesota, weighed the pros and cons of therapy. "The advantages are that it is reasonably well tolerated and seems to be effective. It can be repeated without a ceiling dosage effect."
He pointed out that it is the only treatment so far with evidence supporting an improvement in survival over plastic stent placement alone for advanced cholangiocarcinoma. "In fact, 1 retrospective study suggested that survival [in patients who received] photodynamic therapy and stents was similar to [that in patients] who underwent attempted curative but incomplete surgical resection."
But photodynamic therapy is not available at all centers. It requires expertise in both endoscopy and photodynamic therapy. The procedure is time consuming and can be quite prolonged, depending on number of segments treated. "One should allot at least 90 minutes for the procedure, which entails stent removal, treatment, and stent replacement," the editorialist noted.
Photodynamic Therapy With Stents Appears Effective
"This group uses standard FDA-approved fibers designed for use in the esophagus without the use of cholangioscopy," Dr. Baron writes. "Fiber breakage occurs in about one third of patients."
The fibers available in the United States are suboptimal for endoscopic retrograde cholangiopancreatography. They are stiff and prone to breakage, he warned. Because of the stiffness, treatment is generally limited to the main hepatic ducts; the fiber does not bend around corners to reach intrahepatic branches.
Finally, and perhaps most important, photosensitivity is a problem for 4 to 6 weeks after therapy. Speaking to Medscape Oncology, Dr. Kahaleh pointed out that this adverse effect is a serious issue that requires patient commitment to cover up and stay out of the sun, which can be extremely inconvenient.
Should photodynamic therapy be considered the standard of care for the palliation of cholangiocarcinoma? Dr. Baron says the answer is a qualified yes.
"The data suggest that photodynamic therapy is an excellent option for patients with unresectable cholangiopancreatography, especially for Bismuth III and IV lesions," he writes.
"However, there are no comparative trials with chemoradiation, and photodynamic therapy availability is limited. Therefore, these patients could be managed with standard palliative care at their institution or referred to a specialized center with photodynamic therapy availability."
In the current study, 48 patients with advanced cholangiocarcinoma were treated over a 5-year period. Of these, 29 patients were treated with biliary stents and the remaining 19 were treated with stents and photodynamic therapy.
Kaplan-Meier analysis showed better survival in the combination-therapy group than in the stent-only group (16.2 vs 7.4 months; P < .004).
Three patients experienced adverse events specific to photodynamic therapy in the form of skin phototoxicity requiring topical therapy.
"The study, while one of the first direct comparative survival studies from the US to show an improved survival using photodynamic therapy, has a number of flaws," Dr. Baron pointed out. "It is a small retrospective study. Although the majority of patients had Bismuth III and IV lesions, patients with Bismuth I and II lesions were included. Some patients in each group received chemoradiation therapy."
During an interview, Dr. Kahaleh said he concurs with the points raised in the editorial and sees this study — the first of its kind in the United States — as a starting point from which to promote "bigger and better trials." He is currently working on a multicenter trial that he hopes will begin within 6 months.
The researchers have disclosed no relevant financial relationships.
Clin Gastroenterol Hepatol. 2008;6:266-267 and 290-297
Source: Medscape Medical News 2008. April 2008
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