CEDAZURIDINE/ DECITABINE TAB
Clinical Criteria Summary
Document 261
Indication & Patient Population
- Adult patients with myelodysplastic syndromes (MDS), including previously treated and untreated, de novo and secondary MDS
- French-American-British subtypes: refractory anemia (RA), RA with ringed sideroblasts, RA with excess blasts, and chronic myelomonocytic leukemia (CMML)
- Intermediate-1, intermediate-2, and high-risk International Prognostic Scoring System Groups
- Palliative intent for MDS and CMML; may serve as bridge therapy to allogeneic hematopoietic stem cell transplant (alloHSCT)
Dosing & Administration
- Tablet strength: 35mg decitabine and 100mg cedazuridine
- Regimen: One tablet taken orally once daily on Day 1 through 5 of each 28-day cycle
- Dose reductions are accomplished by reducing the number of days of the treatment cycle rather than using an alternative tablet size
Monitoring & Clinical Management
- Recommended minimum of 4 cycles prior to determining disease response
- Close monitoring required for infections, bleeding, and transfusion needs due to hematologic adverse reactions (more common in the first cycle)
- Renal/Hepatic insufficiency: No current dose recommendations; consider risks versus benefits. Clinical trial inclusion criteria specified Scr < 1.5 or CrCl > 50ml/min/1.73m2 and AST/ALT < 2.5 x ULN, Bilirubin < 2 x ULN
- Avoid coadministration with other drugs metabolized by cytidine deaminase (CDA). Proton pump inhibitors have no clinically meaningful effect on exposure
Contraindications & Warnings/Precautions
- Boxed warnings: None
- Contraindications: None
- Fatal and serious myelosuppression
- Embryo-fetal toxicity; can cause fetal harm when administered to a pregnant woman. Advise patients not to breastfeed
- Can impair fertility
Formulary & Clinical Guidance
- Appropriate for patients diagnosed with MDS or CMML who would be appropriate for azacitidine or IV decitabine
- Consider patient-specific factors including travel time, reliability, degree of social support, access to emergency services, and local VA CBOCs
- May avoid CITC consults and allow continued care provision
- Not adding additional indications beyond hypomethylating agents for MDS/CMML
- Equivalence has not been established with azacitidine IV, SQ, or PO
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Exclusion Criteria
- Hypersensitivity reaction to azacitidine, decitabine or cedazuridine
- Previous use of at least four cycles of decitabine IV or azacitidine without clinical response or benefit
- Concurrent treatment with lenalidomide, injectable azacitidine or injectable decitabine
- Renal dysfunction – Creatinine Clearance <30 mL/min (for Creatinine Clearance 30 – 59 mL/min monitor frequently for adverse reactions)
- Hepatic dysfunction – AST/ALT > 2.5 x upper limit of normal (ULN), Bilirubin > 2 x ULN
- Pregnancy (i.e. known pregnancy or positive pregnancy test)
- Breastfeeding
Inclusion Criteria
- Care is provided by a VA/VA Community Care oncology provider
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 – 2
- Goals of care and role of Palliative Care consult have been discussed and documented
- Patients of child-bearing potential and patients with partners of child-bearing potential: counseling provided on contraception and risks vs benefits of treatment. Use effective contraception during therapy and for 6 months after the last dose.
Additional Inclusion Criteria
- Diagnosis of myelodysplastic syndrome (MDS), including previously treated or untreated, de novo and secondary MDS (RA, RA-RS, RA-EB and CMML) and intermediate-1, intermediate-2, and high-Risk IPSS-R groups
- Parenteral therapy refused by patient or impractical (due to travel or healthcare setting exposure risk)