Key Terms: Benign growth, Cancer screening, CT scan, Electron, Gamma ray, Half-life, Malignant growth,
Definition
Porfimer sodium (trade name Photofrin) is a photo-sensitizing agent that belongs to a group of medicines known as antineoplastics. Porfimer sodium is sometimes called a hematoporphyrin derivative.
Purpose
Porfimer is used in a treatment called photodynamic therapy (PDT). This form of cancer treatment is for patients presenting with obstructing esophageal and endobronchial non-small cell lung cancers (NSCLC) and early stage radiologically occult endobronchial cancer. As of the early 2000s, PDT is considered an experimental treatment for cancer of the esophagus. In 2003, however, the Food and Drug Administration (FDA) added Barrett's esophagus to the list of conditions for which Photofrin is an approved treatment. Some patients with Barrett's esophagus develop precancerous lesions that respond well to treatment with porfimer sodium.
As of 2004, PDT is being studied as a treatment for breast cancer that has progressed to the chest wall. Of one group of 14 patients, nine demonstrated a complete response to PDT.
Another new development is the use of porfimer sodium to treat cancers in the abdominal cavity and the brain. A group of researchers in Boston have used a needle to insert a small-diameter quartz optical fiber that transmits laser light to the pancreas, liver, and spleen to activate the Photofrin. A second team in Salt Lake City has used a new light-delivery device based on light-emitting diode (LED) technology to administer PDT to patients with recurrent brain tumors.
Description
The FDA granted its original approval to porfimer sodium in December 1995. Porfimer is a chemical mixture of up to eight porphyrin units. The freeze-dried compound exists as a dark red to reddish-brown cake or powder and is typically reconstituted with 5% dextrose or 0.9% sodium chloride. Porfimer sodium's anti-tumor effects are dependent upon its activation by a specific wavelength of light that results in the subsequent release of highly toxic oxygen-free radicals. Additionally, PDT using porfimer produces a significant decrease in blood flow to the treatment area that enhances necrosis in certain tumor cells. Clinical test results suggest that use of porfimer sodium for the palliative management of esophageal cancer, and NSCLC yields a statistically significant improvement after a single course of therapy. Porfimer sodium and the associated laser treatment have not been formally tested in conjunction with other photosensitizing compounds. However, it may be speculated that an increase in the photosensitive reaction would result.
Recommended Dosage
The dose of porfimer sodium will vary among patients. The oncologist will make a final dose determination based on a number of factors, including body weight. An appropriate starting regimen for adults would be:
- 2mg porfimer per kg of body weight injected into a vein.
- Approximately 48 hours post injection, tumor illumination with a laser light source set at 630nm wavelength.
- Two to three days post tumor illumination, the physician will remove the destroyed cancer cells.
- If prescribed, a second laser treatment may be given 96–120 hours after the initial porfimer injection followed by subsequent removal of destroyed cancer cells.
- Patients may receive a second dose of porfimer at a minimum of 30 days from the initial treatment for up to three cycles, each 30 days apart.
Precautions
All patients who have received PDT must avoid exposure of the skin and eyes to direct sunlight and bright indoor lighting for a minimum of 30 days. In July 2000, the FDA added the following to patient information labeling of Photofrin: "Some patients may remain photosensitive for up to 90 days or more." Sensitivity is produced from the residual porfimer that has not cleared the patient's system; therefore, ambient indoor lighting will help to gradually quench the photo-sensitive effect. Intermittent exposure trials of a small patch of skin to direct sunlight should be conducted in 10-minute segments beginning 30 days after PDT, and before returning to normal outdoor activities. If no photosensitive reaction (redness, edema, blistering) is apparent 24 hours after exposure, cautious and gradually increased exposure may continue. If the test results are positive, patients should continue precautions for an additional two weeks before repeating the exposure test. Over-the-counter sunscreens are of no use because the photo activation of porfimer occurs in the visible light range. Patient eye sensitivity should be guarded for a minimum of 30 days by wearing dark sunglasses that allow for no greater than 4% of available white light to pass through the lenses. PDT treatment scheduling before or after radiation therapy should be properly spaced to avoid any cumulative inflammatory response from one treatment regimen to the next. A two- to four-week recovery phase between treatment types is recommended. Careful monitoring of endobronchial lesion patients is required to reduce the risk of respiratory distress caused by necrotic tissue obstructing the airway. These patients are also at risk from bleeding problems associated with erosion into a major blood vessel. As with all antineoplastic agents, pregnancy should be avoided. If the patient is pregnant, PDT should only be used if the potential benefits out-weigh the risks to the fetus.
Side Effects
Side effects are associated with all antineoplastic drugs, and patients should be instructed to discuss any concerns. Side effects produced with porfimer that may engender patient concern, but do not typically require medical attention, may include mild diarrhea or constipation, mild nausea and vomiting, blistering, redness or swelling of the skin, difficulty sleeping, weakness, and vision changes. These conditions usually subside as the body adjusts to the porfimer. Side effects associated with porfimer sodium that do require immediate medical attention include:
- shortness of breath or trouble breathing
- fast or irregular heartbeat
- high or low blood pressure
- spitting blood
- severe stomach, abdominal, or chest pain
- chills or fever
- dizziness or fainting
- coughing or wheezing
- unusual weight gain
- excessive fatigue or weakness
- swelling in the face, feet, neck, or lower legs
- white patches in the mouth
- tightness in the chest
- yellow coloration of the eyes or skin
Interactions
There have been no formal interaction studies between porfimer and other drugs. One may speculate on the possible synergistic effects of porfimer in conjunction with other photosensitizing agents, such as phenothiazines, chlorpropramide, demeclocycline, doxycycline, and tetracycline. Animal research studies suggest certain compounds decrease the effectiveness of porfimer used in PDT. These inhibitors include drug compounds such as dimethyl sulfoxide (DMSO) and ethanol that act by inhibiting the formation of free radicals. Other drug groups, such as thromboxane A2 inhibitors, inhibit by decreasing clotting, vasoconstriction, or platelet aggregation. Other pre-clinical trial data suggests a decrease in porfimer efficacy in PDT in response to glucocorticoids hormones, calcium channel blockers, and prostagladin synthesis inhibitors. As with any course of treatment, patients should first notify their doctors of any medications they are taking.
Resources
Books
Beers, Mark H., MD, and Robert Berkow, MD, editors. "Tumors of the Gastrointestinal Tract." Section 3, Chapter 34 In The Merck Manual of Diagnosis and Therapy. Whitehouse Station, NJ: Merck Research Laboratories, 2004.
Periodicals
Chan, H. H., N. S. Nishioka, M. Mino, et al. "EUS-Guided Photodynamic Therapy of the Pancreas: A Pilot Study." Gastrointestinal Endoscopy 59 (January 2004): 95–99.
Cuenca, R. E., R. R. Allison, C. Sibata, and G. H. Downie. "Breast Cancer with Chest Wall Progression: Treatment with Photodynamic Therapy." Annals of Surgical Oncology 11 (March 2004): 322–327.
Schmidt, M. H., G. A. Meyer, K. W. Reichert, et al. "Evaluation of Photodynamic Therapy Near Functional Brain Tissue in Patients with Recurrent Brain Tumors." Journal of Neurooncology 67 (March-April 2004): 201–207.
Organizations
United States Food and Drug Administration (FDA). 5600 Fishers Lane, Rockville, MD 20857-0001. (888) INFO-FDA.
Other
Food and Drug Administration, Center for Drug Evaluation and Research (CDER). CDER Report to the Nation: 2003.
—Jane Taylor-Jones, MS; Rebecca J. Frey, PhD
