Initial US Approval:
2021
Key Clinical Studies:
DOORwaY90 study
Drug Class/Description:
Biocompatible microspheres containing yttrium-90, a beta-emitting isotope
Description:
SIR-Spheres Y-90 resin microspheres consist of biocompatible microspheres containing yttrium-90 with a size between 20 and 60 microns in diameter. Yttrium-90 is a high-energy pure betaemitting isotope with no primary gamma emission. The maximum energy of the beta particles is 2.27 MeV with a mean of 0.93 MeV. The maximum range of emissions in tissue is 11 mm with a mean depth of 2.5 mm. The half-life is 64.1 hours. In therapeutic use, requiring the isotope to decay to infinity, 94% of the radiation is delivered in 11 days. The number of particles provided in each SIR-Y001 5mL vial for implantation is 40-80 million microspheres and the number of particles provided in each SIR-Y002 3mL vial for implantation is 24 – 48 million microspheres. SIR-Spheres Y-90 resin microspheres are a permanent implant.
SIR-Spheres Y-90 resin microspheres are implanted into a hepatic tumor by injection into either the common hepatic artery or the right or left hepatic artery or more selectively using a catheter or chemotherapy catheter port. The SIRSpheres Y-90 resin microspheres distribute nonuniformly in the liver, primarily due to the unique physiological characteristics of the hepatic arterial f low, the tumor to normal liver ratio of the tissue vascularity, and the size of the tumor. The tumor usually gets higher density per unit distribution of SIR-Spheres Y-90 resin microspheres than the normal liver. The density of SIR-Spheres Y-90 resin microspheres in the tumor can be as high as 5 to 6 times of the normal liver tissue. Once SIR-Spheres Y-90 resin microspheres are implanted into the liver, they are not metabolized or excreted, and they stay permanently in the liver. Each device is for single patient use.
Indications for Use:
SIR-Spheres Y-90 resin microspheres are indicated for the local tumor control of unresectable hepatocellular carcinoma (HCC) in patients with no macrovascular invasion, Child Pugh-A cirrhosis, well-compensated liver function, and good performance status. They are also indicated for the treatment of unresectable metastatic liver tumors from primary colorectal cancer with adjuvant intra-hepatic artery chemotherapy (IHAC) of FUDR (Floxuridine).
Contraindications:
Contraindications for All Patients
- SIR-Spheres Y-90 resin microspheres are contraindicated in any patient who has:
- portal vein thrombosis
- ascites or clinical liver failure
- markedly abnormal synthetic and excretory liver function tests (LFTs), such as total bilirubin > 2.0 mg/dL or albumin < 3.0 g/dL
- > 20% lung shunting of the hepatic artery blood f low, or > 30 Gy radiation absorbed dose to the lungs for a single treatment, or > 50 Gy cumulative radiation absorbed dose to the lungs if the patient is re-treated, as estimated by the 99mMAA scan
- pre assessment angiogram that demonstrates abnormal vascular anatomy that would result insignificant reflux of microspheres to the stomach, pancreas or bowel
- had previous external beam radiation therapy to the livers
Contraindications for Patients with mCR
- disseminated extra-hepatic malignant disease
- been treated with capecitabine within the two previous months, or who will be treated with capecitabine at any time following treatment with SIR-Spheres Y-90 resin microspheres
Contraindications for Patients with HCC
- comorbidities or poor overall health (e.g., ECOG performance status rating > 2) which may make the patient a poor candidate for locoregional radiation treatment
- disseminated extra-hepatic malignant disease
Warnings
Non-Target Delivery of SIR-Spheres Y-90 Resin Microspheres
Inadvertent delivery of SIR-Spheres Y-90 resin microspheres to extra-hepatic structures such as the esophagus, stomach, duodenum, gallbladder or pancreas may result in radiation injury to these structures. Meticulous angiographic technique must be employed to prevent the non-target delivery of SIR-Spheres Y-90 resin microspheres to any extra-hepatic structures.
Radioembolization Induced Liver Disease (REILD)
Delivery of excessive radiation to the normal liver parenchyma may result in REILD. The risk of REILD may also be increased in patients with pre-existing liver disease. Consideration should be given to reducing the prescribed activity of SIR-Spheres Y-90 resin microspheres in the following clinical settings:
- Reduced liver functional reserve due to steatosis, steatohepatitis, hepatitis or cirrhosis
- Elevated baseline bilirubin level
- Non-selective treatment of small tumor burden (< 5% liver involvement)
- Small liver volume (< 1.5 L)
- Prior hepatic resection
- Prior liver directed therapy
Radiation Pneumonitis
High levels of implanted radiation and/or excessive shunting to the lung may lead to radiation pneumonitis. Limit radiation dose to ≤ 30 Gy per treatment and ≤ 50 Gy cumulatively.
Limited Radiation Dosimetry Planning Precision
has been found to differ compared to the amount planned. Similar levels of precision should not be assumed when planning for Y-90 microsphere radiation therapy compared to when planning for external beam radiation therapy.
Adapted From:
https://www.sirtex.com/Media/55rprxv2/SSL-US-17%20SIR-Spheres%20US-IFU%20R4.pdf
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