No

Antineoplastic Agent, Miscellaneous

Esophageal cancer: Photodynamic therapy (PDT) with porfimer for palliation of patients with completely obstructing esophageal cancer, or of patients with partially obstructing esophageal cancer who cannot be satisfactorily treated with Nd:YAG laser therapy

C

Porphyria or in patients with known allergies to porphyrins; existing tracheoesophageal or bronchoesophageal fistula; tumors eroding into a major blood vessel

The U.S. Food and Drug Administration (FDA) currently recommends that procedures for proper handling and disposal of antineoplastic agents be considered. If the esophageal tumor is eroding into the trachea or bronchial tree, the likelihood of tracheoesophageal or bronchoesophageal fistula resulting from treatment is sufficiently high that PDT is not recommended. All patients who receive porfimer sodium will be photosensitive and must observe precautions to avoid exposure of skin and eyes to direct sunlight or bright indoor light for 30 days. The photosensitivity is due to residual drug which will be present in all parts of the skin. Exposure of the skin to ambient indoor light is, however, beneficial because the remaining drug will be inactivated gradually and safely through a photobleaching reaction. Patients should not stay in a darkened room during this period and should be encouraged to expose their skin to ambient indoor light. Ocular discomfort has been reported; for 30 days, when outdoors, patients should wear dark sunglasses which have an average white light transmittance of <4%.

>10%:

Cardiovascular: Atrial fibrillation, chest pain

Central nervous system: Fever, pain, insomnia

Dermatologic: Photosensitivity reaction

Gastrointestinal: Abdominal pain, constipation, dysphagia, nausea, vomiting

Hematologic: Anemia

Neuromuscular & skeletal: Back pain

Respiratory: Dyspnea, pharyngitis, pleural effusion, pneumonia, respiratory insufficiency

1% to 10%:

Cardiovascular: Hypertension, hypotension, edema, cardiac failure, tachycardia, chest pain (substernal)

Central nervous system: Anxiety, confusion

Endocrine & metabolic: Dehydration

Gastrointestinal: Diarrhea, dyspepsia, eructation, esophageal edema, esophageal tumor bleeding, esophageal stricture, esophagitis, hematemesis, melena, weight loss, anorexia

Genitourinary: Urinary tract infection

Neuromuscular & skeletal: Weakness

Respiratory: Coughing, tracheoesophageal fistula

Miscellaneous: Moniliasis, surgical complication

Overdose of laser light following porfimer injection: Increased symptoms and damage to normal tissue might be expected following an overdose of light

Treatment: Effects of overdosage on the duration of photosensitivity are unknown. Laser treatment should not be given if an overdose of porfimer is administered. In the event of an overdose, patients should protect their eyes and skin from direct sunlight or bright indoor lights for 30 days. At this time, patients should test for residual photosensitivity. Porfimer is not dialyzable.

Decreased effect: Compounds that quench active oxygen species or scavenge radicals (eg, dimethyl sulfoxide, beta-carotene, ethanol, mannitol) would be expected to decrease PDT activity; allopurinol, calcium channel blockers and some prostaglandin synthesis inhibitors could interfere with porfimer; drugs that decrease clotting, vasoconstriction or platelet aggregation could decrease the efficacy of PDT; glucocorticoid hormones may decrease the efficacy of the treatment

Increased toxicity: Concomitant administration of other photosensitizing agents (eg, tetracyclines, sulfonamides, phenothiazines, sulfonylureas, thiazide diuretics, griseofulvin) could increase the photosensitivity reaction

Store intact vials at controlled room temperature of 20°C to 25°C/68°F to 77°F

Photosensitizing agent used in the photodynamic therapy (PDT) of tumors: cytotoxic and antitumor actions of porfimer are light and oxygen dependent. Cellular damage caused by porfimer PDT is a consequence of the propagation of radical reactions.

Distribution: Steady state V_d: 0.49 L/kg

Protein binding, plasma: 90%

Half-life: 250 hours

Time to peak serum concentration: Within 2 hours

Elimination: Total plasma clearance: 0.051 mL/minute/kg

I.V. (refer to individual protocols):

Adults: I.V.: 2 mg/kg over 3-5 minutes

Photodynamic therapy is a two-stage process requiring administration of both drug and light. The first stage of PDT is the I.V. injection of porfimer. Illumination with laser light 40-50 hours following the injection with porfimer constitutes the second stage of therapy. A second laser light application may be given 90-120 hours after injection, preceded by gentle debridement of residual tumor.

Patients may receive a second course of PDT a minimum of 30 days after the initial therapy; up to three courses of PDT (each separated by a minimum of 30 days) can be given. Before each course of treatment, evaluate patients for the presence of a tracheoesophageal or bronchoesophageal fistula.

Insomnia is common; may cause anxiety or confusion

May cause anemia; use caution with clozapine and carbamazepine; concurrent use with psychotropics may increase the risk of photosensitivity reactions

No information available to require special precautions

No effects or complications reported

This medication can only be administered I.V. and will be followed by laser light therapy. Avoid any exposure to sunlight or bright indoor light for 30 days following therapy (cover skin with protective clothing and wear dark sunglasses with light transmittance <4% when outdoors - severe blistering, burning, and skin/eye damage can result). After 30 days, test small area of skin (not face) for remaining sensitivity. Retest sensitivity if traveling to a different geographic area with greater sunshine. Exposure to indoor normal light is beneficial since it will help dissipate photosensitivity gradually. Maintain adequate hydration (2-3 L/day of fluids unless instructed to restrict fluid intake); maintain good oral hygiene (use soft toothbrush or cotton applicators several times a day and rinse mouth frequently). Small frequent meals, frequent mouth care, sucking lozenges, or chewing gum may reduce nausea or vomiting. Report rapid heart rate, chest pain or palpitations, difficulty breathing or air hunger, persistent fever or chills, foul-smelling urine or burning on urination, swelling of extremities, increased anxiety, confusion, or hallucination. Pregnancy/breast-feeding precautions: Inform prescriber if pregnant. Do not breast-feed.

Powder for injection, as sodium: 75 mg

Evensen JF, "The Use of Porphyrins and Nonionizing Radiation for Treatment of Cancer," Acta Oncol, 1995, 34(8):1103-10.

Levy JG, "Photosensitizers in Photodynamic Therapy," Semin Oncol, 1994, 21(6 Suppl 15):4-10.

Rosenthal DI and Glatstein E, "Clinical Applications of Photodynamic Therapy," Ann Med, 1994, 26(6):405-9.

Van Hillegersberg R, Kort WJ, and Wilson JH, "Current Status of Photodynamic Therapy in Oncology," Drugs, 1994, 48(4):510-27.