Porfimer

Esophageal Strictures : Esophageal strictures can occur Hepatic and Renal Impairment : Patients with hepatic or renal impairment may need longer precautionary measures for photosensitivity. Thromboembolism : Thromboembolic events can occur. Embryo-Fetal Toxicity : May cause embryo-fetal toxicity. Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception. ( 5.12 , 8.1 ) 5.1 Gastroesophageal Fistula and Perforation Serious and sometimes fatal gastrointestinal and esophageal necrosis and perforation can occur following treatment with PHOTOFRIN with PDT.

Multiple dilations of esophageal strictures may be required, as shown in Table 5 TABLE 5 . Esophageal Dilations in Patients with Treatment – Related Strictures Number of Dilations Number of Patients With Strictures N=114 Percentage of Patients with Strictures 1 – 2 Dilations 32 28% 3 – 5 Dilations 32 28% 6 - 10 24 21% >10 Dilations 26 23% 5.10 Risk of Prolonged Duration of Photosensitivity in Patients with Hepatic and Renal Impairment Hepatic or renal impairment will likely prolong the elimination of porfimer sodium leading to higher rates of toxicity.

Inform patients with severe renal impairment or mild to severe hepatic impairment that the period requiring the precautionary measures for photosensitivity may be longer than 90 days. 5.11 Thromboembolism Thromboembolic events can occur following photodynamic therapy with PHOTOFRIN. Most reported events occurred in patients with other risk factors for thromboembolism including advanced cancer, following major surgery, prolonged immobilization, or cardiovascular disease. 5.12 Embryo-Fetal Toxicity Based on animal studies, PHOTOFRIN may cause embryo-fetal toxicity when administered to a pregnant woman.

Photoactivation Esophageal Cancer Initiate 630 nm wavelength laser light delivery to the patient 40-50 hours following injection with PHOTOFRIN. A second laser light treatment may be given as early as 96 hours or as late as 120 hours after the initial injection with PHOTOFRIN. No further injection of PHOTOFRIN should be given for such retreatment with laser light.

Before providing a second laser light treatment, the residual tumor may be debrided. The debridement is optional since the residua will be removed naturally by peristaltic action of the esophagus. Vigorous debridement may cause tumor bleeding. Photoactivation of PHOTOFRIN is controlled by the total light dose delivered.

In the treatment of esophageal cancer, a light dose of 300 Joules/cm (J/cm) of diffuser length should be delivered. The total power output at the fiber tip is set to deliver the appropriate light dose using exposure times of 12 minutes and 30 seconds. For the treatment of esophageal cancer, 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, patients with esophageal cancer should be evaluated for the presence of a tracheoesophageal or bronchoesophageal fistula [see Contraindications] . All patients should be evaluated for the possibility that the tumor may be eroding into a major blood vessel [see Contraindications ]. Endobronchial Cancer Initiate 630 nm wavelength laser light delivery to the patient 4050 hours following injection with PHOTOFRIN.

A second laser light treatment may be given as early as 96 hours or as late as 120 hours after the initial injection with PHOTOFRIN. No further injection of PHOTOFRIN should be given for such retreatment with laser light. Before providing a second laser light treatment, the residual tumor should be debrided. Vigorous debridement may cause tumor bleeding.

For endobronchial tumors, debridement of necrotic tissue should be discontinued when the volume of bleeding increases, as this may indicate that debridement has gone beyond the zone of the PDT effect. Photoactivation of PHOTOFRIN is controlled by the total light dose delivered. In the treatment of endobronchial cancer, a light dose of 200 J/cm of diffuser length should be delivered.

The total power output at the fiber tip is set to deliver the appropriate light dose using exposure times of 8 minutes and 20 seconds. For noncircumferential endobronchial tumors that are soft enough to penetrate, interstitial fiber placement is preferred to intraluminal activation, since this method produces better efficacy and results in less exposure of the normal bronchial mucosa to light.

It is important to perform a debridement 2 to 3 days after each light administration to minimize the potential for obstruction caused by necrotic debris [see Warnings and Precautions ]. For the treatment of endobronchial cancer, 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.

In patients with endobronchial lesions who have recently undergone radiotherapy, sufficient time (approximately 4 weeks) should be allowed between the therapies to ensure that the acute inflammation produced by radiotherapy has subsided prior to PDT [see Warnings and Precautions] . All patients should be evaluated for the possibility that the tumor may be eroding into a major blood vessel [see Contraindications ] .

High-Grade Dysplasia (HGD) in Barretts Esophagus (BE) Prior to initiating treatment with PHOTOFRIN PDT, the diagnosis of HGD in BE should be confirmed by an expert GI pathologist. Approximately 40-50 hours after PHOTOFRIN administration light should be delivered by a X-Cell Photodynamic Therapy (PDT) Balloon with Fiber Optic Diffuser.

The choice of fiber optic/balloon diffuser combination will depend on the length of Barretts mucosa to be treated ( Table 1 ). [See table below.] 5 3 Photoactivation is controlled by the total light dose delivered. The objective is to expose and treat all areas of HGD and the entire length of BE. The light dose administered will be 130 J/cm of diffuser length using a centering balloon.

Based on the randomized clinical study, acceptable light intensity for the balloon/diffuser combinations range from 200-270 mW/cm of diffuser length. To calculate the light dose, the following specific light dosimetry equation applies for all fiber optic diffusers: Light Dose (J/cm) = Power Output From Diffuser (W) x Treatment Time (s ) Diffuser Length (cm) Table 2 provides the settings that will be used to deliver the dose within the shortest time (light intensity of 270 mW/cm).

A second option (light intensity of 200 mW/cm) has also been included where necessary to accommodate lasers with a total capacity that does not exceed

Important Administration Instructions Photodynamic therapy (PDT) with PHOTOFRIN is a two-stage process requiring administration of both drug and light. The first stage of PDT is the intravenous injection of PHOTOFRIN at 2 mg/kg. Illumination with laser light 40–50 hours following injection with PHOTOFRIN constitutes the second stage of therapy.

A second laser light application may be given 96-120 hours after injection [ see Dosage and Administration] . In clinical studies on endobronchial cancer, debridement via endoscopy was required 2-3 days after the initial light application. Standard endoscopic techniques are used for light administration and debridement.

Healthcare providers should be fully familiar with the patient’s condition and trained in the safe and efficacious treatment of esophageal or endobronchial cancer, or high-grade dysplasia (HGD) in Barrett’s esophagus (BE) using PDT with PHOTOFRIN and associated light delivery devices. PDT with PHOTOFRIN should be applied only in those facilities properly equipped for the procedure.

The laser system must be approved for delivery of a stable power output at a wavelength of 630 ± 3 nm. Light is delivered to the tumor by cylindrical OPTIGUIDE™ fiber optic diffusers passed through the operating channel of an endoscope/bronchoscope. Instructions for use of the fiber optic and the selected laser system should be read carefully before use.

OPTIGUIDE™ cylindrical diffusers are available in several lengths. The choice of diffuser tip length depends on the length of the tumor or Barrett’s mucosa to be treated. Diffuser length should be sized to avoid exposure of nonmalignant tissue to light and to prevent overlapping of previously treated malignant tissue. Refer to the OPTIGUIDE™ instructions for use for complete instructions concerning the fiber optic diffuser.