Porfimer
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Steven Bellm, M.D. [2]
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Overview
Porfimer is a photosensitizing agent that is FDA approved for the treatment of obstructive esophageal cancer, completely or partially obstructing endobronchial non-small-cell lung cancer (NSCLC), Barrett's esophagus. Common adverse reactions include constipation, dysphagia, esophageal stricture, anemia, backache, insomnia, bronchitis, dyspnea, obstruction of bronchus, pharyngitis, stenosis of bronchus, fever, pain.
Adult Indications and Dosage
FDA-Labeled Indications and Dosage (Adult)
- Barrett's esophagus, Ablation of high-grade dysplasia in patients not undergoing surgery: 2 mg/kg IV over 3 to 5 minutes followed by local application of laser light (630 nanometers wavelength) to the tumor 40 to 50 hours later; a second laser light application may be given 96 to 120 hours after administration of porfimer; patients may receive an additional course a minimum of 90 days after therapy; MAX number of courses is 3 (each separated by 90 days).
- Barrett's esophagus, Ablation of high-grade dysplasia in patients not undergoing surgery: The manufacturer recommends a light dose of 130 Joules/centimeter; acceptable light intensity for the balloon/diffuser combinations are 200 to 270 milliwatts/centimeter of diffuser. If repeated, use a light dose of 50 Joules/centimeter of fiber optic diffuser length 96 to 120 hours after initial injection.
- Carcinoma of esophagus, Completely or partially obstructed disease in patients ineligible for Nd/YAG laser therapy (palliative): 2 mg/kg IV over 3-5 minutes followed by local application of laser light (630 nanometers wavelength) to the tumor 40 to 50 hours later. A second laser light application may be given 96 to 120 hours after administration of porfimer, preceded by careful debridement of residual tumor; patients may receive an additional course a minimum of 30 days after therapy; max. number of courses is 3 (each separated by 30 days).
- Carcinoma of esophagus, Completely or partially obstructed disease in patients ineligible for Nd/YAG laser therapy (palliative): The manufacturer recommends 300 Joules/centimeter (J/cm) of tumor length with the fiber tip set to deliver the light dose using exposure times of 12 minutes and 30 seconds.
- Cholangiocarcinoma of biliary tract, Unresectable, after double stenting: 2 mg/kg IV administered 48 hours before laser activation was used in a clinical trial; photoactivation was performed at 630 nanometers using a light dose of 180 joules/cm(2).
- Non-small cell lung cancer, Completely or partially obstructing endobronchial disease: 2 mg/kg IV over 3 to 5 minutes followed by local application of laser light (630 nanometers wavelength) to the tumor 40 to 50 hours later; a second laser light application may be given 96 to 120 hours after administration of porfimer, preceded by careful debridement of residual tumor; patients may receive an additional course a minimum of 30 days after therapy; MAX number of courses is 3 (each separated by 30 days).
- Non-small cell lung cancer, Microinvasive endobronchial disease; in patients ineligible for surgery or radiotherapy: 2 mg/kg IV over 3 to 5 minutes followed by local application of laser light (630 nanometers wavelength) to the tumor 40 to 50 hours later; a second laser light application may be given 96 to 120 hours after administration of porfimer, preceded by careful debridement of residual tumor; patients may receive an additional course a minimum of 30 days after therapy; MAX number of courses is 3 (each separated by 30 days)
- Non-small cell lung cancer, Microinvasive endobronchial disease; in patients ineligible for surgery or radiotherapy: The manufacturer recommends 200 Joules/centimeter (J/cm) of tumor length for both palliation and treatment; with the fiber tip set to deliver the light dose using exposure times of 8 minutes and 20 seconds.
Off-Label Use and Dosage (Adult)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Porfimer in adult patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Porfimer in adult patients.
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
Safety and effectiveness in children have not been established.
Off-Label Use and Dosage (Pediatric)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Porfimer in pediatric patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Porfimer in pediatric patients.
Contraindications
PHOTOFRIN® is contraindicated in patients with porphyria or in patients with known allergies to porphyrins.
Photodynamic therapy is contraindicated in patients with an existing tracheoesophageal or bronchoesophageal fistula.
Photodynamic therapy is contraindicated in patients with tumors eroding into a major blood vessel.
Photodynamic therapy is not suitable for emergency treatment of patients with severe acute respiratory distress caused by an obstructing endobronchial lesion because 40 to 50 hours are required between injection with PHOTOFRIN® and laser light treatment.
Photodynamic therapy is not suitable for patients with esophageal or gastric varices, or patients with esophageal ulcers >1 cm in diameter.
Warnings
Following injection with PHOTOFRIN® precautions must be taken to avoid exposure of skin and eyes to direct sunlight or bright indoor light (see PRECAUTIONS, GENERAL PRECAUTIONS AND INFORMATION FOR PATIENTS).
Esophageal Cancer
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.
Patients with esophageal varices should be treated with extreme caution. Light should not be given directly to the variceal area because of the high risk of bleeding.
Endobronchial Cancer
Patients should be assessed for the possibility that a tumor may be eroding into a pulmonary blood vessel (see CONTRAINDICATIONS). Patients at high risk for fatal massive hemoptysis (FMH) include those with large, centrally located tumors, those with cavitating tumors or those with extensive tumor extrinsic to the bronchus.
If the endobronchial tumor invades deeply into the bronchial wall, the possibility exists for fistula formation upon resolution of tumor.
Photodynamic therapy should be used with extreme caution for endobronchial tumors in locations where treatment-induced inflammation could obstruct the main airway, e.g., long or circumferential tumors of the trachea, tumors of the carina that involve both mainstem bronchi circumferentially, or circumferential tumors in the mainstem bronchus in patients with prior pneumonectomy.
High-Grade Dysplasia (HGD) in Barrett’s Esophagus (BE)
The long-term effect of PDT on HGD in BE is unknown. There is always a risk of cancer or abnormal epithelium that is invisible to the endoscopist beneath the new squamous cell epithelium; these facts emphasize the risk of overlooking cancer in such patients and the need for rigorous continuing surveillance despite the endoscopic appearance of complete squamous cell reepithelialization. It is recommended that endoscopic biopsy surveillance be conducted every three months, until four consecutive negative evaluations for HGD have been recorded; further follow-up may be scheduled every 6 to 12 months, as per judgment of physicians. The follow-up period of the pivotal study at the time of analysis was a minimum of two years (ranging from 2 to 3.6 years).
Adverse Reactions
Clinical Trials Experience
Systemically induced effects associated with PDT with PHOTOFRIN® consist of photosensitivity and mild constipation. All patients who receive PHOTOFRIN® will be photosensitive and must observe precautions to avoid sunlight and bright indoor light. Photosensitivity reactions occurred in approximately 20% of cancer patients and in 68% of high-grade dysplasia (HGD) in Barrett’s esophagus (BE) patients treated with PHOTOFRIN®. Typically these reactions were mostly mild to moderate erythema but they also included swelling, itching, burning sensation, feeling hot, or blisters. In a single study of 24 healthy subjects, some evidence of photosensitivity reactions occurred in all subjects. Other less common skin manifestations were also reported in areas where photosensitivity reactions had occurred, such as increased hair growth, skin discoloration, skin nodules, increased wrinkles and increased skin fragility. These manifestations may be attributable to a pseudoporphyria state (temporary drug-induced cutaneous porphyria).
Most toxicities associated with this therapy are local effects seen in the region of illumination and occasionally in surrounding tissues. The local adverse reactions are characteristic of an inflammatory response induced by the photodynamic effect.
A few cases of fluid imbalance have been reported following the use of PDT with PHOTOFRIN® in patients with overtly disseminated intraperitoneal malignancies. Fluid imbalance is an expected PDT treatment-related event.
A case of cataracts has been reported in a 51 year-old obese man treated with PHOTOFRIN® PDT for HGD in BE. The patient suffered from a PDT response with development of a deep esophageal ulcer. Within two months post PDT, the patient noted difficulty with his distant vision. A thorough eye examination revealed a change in the refractive error that later progressed to cataracts in both eyes. Both of his parents had a history of cataracts in their 70s. Whether PHOTOFRIN® directly caused or accelerated a familial underlying condition is unknown.
Esophageal Carcinoma
The following adverse events were reported over the entire follow-up period in at least 5% of patients treated with PHOTOFRIN® PDT, who had completely or partially obstructing esophageal cancer. Table 7 presents data from 88 patients who received the currently marketed formulation. The relationship of many of these adverse events to PDT with PHOTOFRIN® is uncertain.
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Location of the tumor was a prognostic factor for three adverse events: upper-third of the esophagus (esophageal edema), middle-third (atrial fibrillation), and lower-third, the most vascular region (anemia). Also, patients with large tumors (>10 cm) were more likely to experience anemia. Two of 17 patients with complete esophageal obstruction from tumor experienced esophageal perforations, which were considered to be possibly treatment associated; these perforations occurred during subsequent endoscopies.
Serious and other notable adverse events observed in less than 5% of PDT-treated patients with obstructing esophageal cancer in the clinical studies include the following; their relationship to therapy is uncertain. In the gastrointestinal system, esophageal perforation, gastric ulcer, ileus, jaundice, and peritonitis have occurred. Sepsis has been reported occasionally. Cardiovascular events have included angina pectoris, bradycardia, myocardial infarction, sick sinus syndrome, and supraventricular tachycardia. Respiratory events of bronchitis, bronchospasm, laryngotracheal edema, pneumonitis, pulmonary hemorrhage, pulmonary edema, respiratory failure, and stridor have occurred. The temporal relationship of some gastrointestinal, cardiovascular and respiratory events to the administration of light was suggestive of mediastinal inflammation in some patients. Vision-related events of abnormal vision, diplopia, eye pain and photophobia have been reported.
Obstructing Endobronchial Cancer
Table 8 presents adverse events that were reported over the entire follow-up period in at least 5% of patients with obstructing endobronchial cancer treated with PHOTOFRIN® PDT or Nd:YAG. These data are based on the 86 patients who received the currently marketed formulation. Since it seems likely that most adverse events caused by these acute acting therapies would occur within 30 days of treatment, Table 8 presents those events occurring within 30 days of a treatment procedure, as well as those occurring over the entire follow-up period. It should be noted that follow-up was 33% longer for the PDT group than for the Nd:YAG group, thereby introducing a bias against PDT when adverse event rates are compared for the entire follow-up period. The extent of follow-up in the 30-day period following treatment was comparable between groups (only 9% more for PDT).
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Transient inflammatory reactions in PDT-treated patients occur in about 10% of patients and manifest as fever, bronchitis, chest pain, and dyspnea. The incidences of bronchitis and dyspnea were higher with PDT than with Nd:YAG. Most cases of bronchitis occurred within 1 week of treatment and all but one were mild or moderate in intensity. The events usually resolved within 10 days with antibiotic therapy. Treatment-related worsening of dyspnea is generally transient and self-limiting. Debridement of the treated area is mandatory to remove exudate and necrotic tissue. Life-threatening respiratory insufficiency likely due to therapy occurred in 3% of PDT-treated patients and 2% of Nd:YAG-treated patients.
There was a trend toward a higher rate of fatal massive hemoptysis (FMH) occurring on the PDT arm (10%) versus the Nd:YAG arm (5%), however, the rate of FMH occurring within 30 days of treatment was the same for PDT and Nd:YAG (4% total events, 3% treatment-associated events). Patients who have received radiation therapy have a higher incidence of FMH after treatment with PDT and after other forms of local therapy than patients who have not received radiation therapy, but analyses suggest that this increased risk may be due to associated prognostic factors such as having a centrally located tumor. The incidence of FMH in patients previously treated with radiotherapy was 21% (6/29) in the PDT group and 10% (3/29) in the Nd:YAG group. In patients with no prior radiotherapy, the overall incidence of FMH was less than 1%.
Other serious or notable adverse events were observed in less than 5% of PDT-treated patients with endobronchial cancer; their relationship to therapy is uncertain. In the respiratory system, pulmonary thrombosis, pulmonary embolism, and lung abscess have occurred. Cardiac failure, sepsis, and possible cerebrovascular accident have also been reported in one patient each.
Superficial Endobronchial Tumors
The following adverse events were reported over the entire follow-up period in at least 5% of patients with superficial tumors (microinvasive or carcinoma in situ) who received the currently marketed formulation.
In patients with superficial endobronchial tumors, 44 of 90 patients (49%) experienced an adverse event, two-thirds of which were related to the respiratory system. The most common reaction to therapy was a mucositis reaction in one-fifth of the patients, which manifested as edema, exudate, and obstruction. The obstruction (mucus plug) is easily removed with suction or forceps. Mucositis can be minimized by avoiding exposure of normal tissue to excessive light (see PRECAUTIONS). Three patients experienced life-threatening dyspnea: one was given a double dose of light, one was treated concurrently in both mainstem bronchi and the other had had prior pneumonectomy and was treated in the sole remaining main airway. Stent placement was required in 3% of the patients due to endobronchial stricture. Fatal massive hemoptysis occurred within 30 days of treatment in one patient with superficial tumors (1%).
High-Grade Dysplasia (HGD) in Barrett’s Esophagus (BE)
Table 10 presents adverse events that were reported, regardless of the relationship to treatment, over the follow-up period in at least 5% of patients with HGD in BE in either controlled or uncontrolled clinical trials.
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In the PHOTOFRIN® PDT + OM group, severe treatment-associated adverse events included chest pain of non-cardiac origin, dysphagia, nausea, vomiting, regurgitation, and heartburn. The severity of these symptoms decreased within 4 to 6 weeks following treatment.
The majority of the photosensitivity reactions occurred within 90 days following PHOTOFRIN® injection and was of mild (69%) or moderate (24%) intensity. Almost all (98%) of the photosensitivity reactions were considered to be associated with treatment. Fourteen (10%) patients reported severe reactions, all of which resolved. The typical reaction was described as skin disorder, sunburn or rash, and affected mostly the face, hands, and neck. Associated symptoms and signs were swelling, pruritis, erythema, blisters, itching, burning sensation, and feeling of heat.
The majority of esophageal stenosis and strictures reported in the PHOTOFRIN® PDT + OM group were of mild (55%) or moderate (37%) intensity, while approximately 8% were of severe intensity. The majority of esophageal strictures were reported during Course 2 of treatment. All esophageal strictures were considered to be associated with treatment. Most esophageal strictures were manageable through dilations (see PRECAUTIONS).
Laboratory Abnormalities
In patients with esophageal cancer, PDT with PHOTOFRIN® may result in anemia due to tumor bleeding. No significant effects were observed for other parameters in patients with endobronchial carcinoma or with HGD in BE.
Postmarketing Experience
There is limited information regarding Porfimer Postmarketing Experience in the drug label.
Drug Interactions
There is limited information regarding Porfimer Drug Interactions in the drug label.
Use in Specific Populations
Pregnancy
Pregnancy Category (FDA): C There are no adequate and well-controlled studies in pregnant women. PHOTOFRIN® should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
PHOTOFRIN® given to rat dams during fetal organogenesis intravenously at 8 mg/kg/d (0.64 times the clinical dose on a mg/m2 basis) for 10 days caused no major malformations or developmental changes. This dose caused maternal and fetal toxicity resulting in increased resorptions, decreased litter size, delayed ossification, and reduced fetal weight. PHOTOFRIN® caused no major malformations when given to rabbits intravenously during organogenesis at 4 mg/kg/d (0.65 times the clinical dose on a mg/m2 basis) for 13 days. This dose caused maternal toxicity resulting in increased resorptions, decreased litter size, and reduced fetal body weight.
PHOTOFRIN® given to rats during late pregnancy through lactation intravenously at 4 mg/kg/d (0.32 times the clinical dose on a mg/m2 basis) for at least 42 days caused a reversible decrease in growth of offspring. Parturition was unaffected.
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Porfimer in women who are pregnant.
Labor and Delivery
There is no FDA guidance on use of Porfimer during labor and delivery.
Nursing Mothers
There is no FDA guidance on the use of Porfimer in women who are nursing.
Pediatric Use
There is no FDA guidance on the use of Porfimer in pediatric settings.
Geriatic Use
There is no FDA guidance on the use of Porfimer in geriatric settings.
Gender
There is no FDA guidance on the use of Porfimer with respect to specific gender populations.
Race
There is no FDA guidance on the use of Porfimer with respect to specific racial populations.
Renal Impairment
There is no FDA guidance on the use of Porfimer in patients with renal impairment.
Hepatic Impairment
There is no FDA guidance on the use of Porfimer in patients with hepatic impairment.
Females of Reproductive Potential and Males
There is no FDA guidance on the use of Porfimer in women of reproductive potentials and males.
Immunocompromised Patients
There is no FDA guidance one the use of Porfimer in patients who are immunocompromised.
Administration and Monitoring
Administration
There is limited information regarding Porfimer Administration in the drug label.
Monitoring
There is limited information regarding Porfimer Monitoring in the drug label.
IV Compatibility
There is limited information regarding the compatibility of Porfimer and IV administrations.
Overdosage
There is limited information regarding Porfimer overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.
Pharmacology
There is limited information regarding Porfimer Pharmacology in the drug label.
Mechanism of Action
There is limited information regarding Porfimer Mechanism of Action in the drug label.
Structure
There is limited information regarding Porfimer Structure in the drug label.
Pharmacodynamics
There is limited information regarding Porfimer Pharmacodynamics in the drug label.
Pharmacokinetics
There is limited information regarding Porfimer Pharmacokinetics in the drug label.
Nonclinical Toxicology
There is limited information regarding Porfimer Nonclinical Toxicology in the drug label.
Clinical Studies
There is limited information regarding Porfimer Clinical Studies in the drug label.
How Supplied
There is limited information regarding Porfimer How Supplied in the drug label.
Storage
There is limited information regarding Porfimer Storage in the drug label.
Images
Drug Images
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Package and Label Display Panel
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Patient Counseling Information
There is limited information regarding Porfimer Patient Counseling Information in the drug label.
Precautions with Alcohol
Alcohol-Porfimer interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
Brand Names
There is limited information regarding Porfimer Brand Names in the drug label.
Look-Alike Drug Names
There is limited information regarding Porfimer Look-Alike Drug Names in the drug label.
Drug Shortage Status
Price
References
The contents of this FDA label are provided by the National Library of Medicine.