Azacitidine for Treatment of Myelodysplastic Syndrome (MDS)

Transcription

1 Azacitidine for Treatment of Myelodysplastic Syndrome (MDS) Cumbria, Northumberland, Tyne & Wear Area Team DRUG ADMINISTRATION SCHEDULE Day Drug Dose Route Site Notes 1 to 5 Azacitidine 75 mg/m 2 subcutaneous 8 & 9 Azacitidine 75 mg/m 2 subcutaneous Upper arm, thigh or abdomen. Rotate sites of injection Doses greater than 4 ml should be injected into two separate sites The recommended starting dose for the first treatment cycle, for all patients regardless of baseline haematology laboratory values, is 75 mg/m 2 of body surface area, injected subcutaneously, for a total of 7 days. CYCLE LENGTH AND NUMBER OF DAYS Azacitidine is to be given Mon-Fri for 5 days, with a 2-day break at weekends, followed by treatment on Mon, Tues (AZA 5-2-2). Each 7-day treatment is followed by a rest period of 19 days (28-day treatment cycle). It is recommended that patients be treated for a minimum of 6 cycles. Treatment should be continued as long as the patient continues to benefit or until disease progression. APPROVED INDICATIONS Myelodysplastic syndrome with IPSS Int-2 or high risk Chronic myelomonocytic leukaemia with marrow blasts 10-19%, no evidence of myeloproliferative disorder Acute myeloid leukaemia with marrow blasts 10-29%, multilineage dysplasia The indication for azacitidine must meet these criteria strictly, be discussed and agreed at the MDT before starting treatment. ELIGIABILITY CRITERIA See approved indications and exclusion criteria. EXCLUSION CRITERIA Patients who are eligible for allogeneic haemopoietic stem cell transplantation Patients with ECOG 2 Patients with a life expectancy < 3 months due to a co-existing disease Pregnancy / Breast Feeding Patients with advanced malignant hepatic tumours Azacitidine for treatment of Myelodysplastic Syndrome Page 1 of 6

2 PREMEDICATION Azacitidine may be categorized as moderately emetogenic. The recommended antiemetic agent is ondansetron 8 mg twice daily. RECOMMENDED TAKE HOME MEDICATION Ondansetron 8 mg orally 30 minutes before each dose of azacitadine is probably sufficient for most patients. INVESTIGATIONS / MONITORING REQUIRED Prior to first cycle: FBC, U&Es, LFTs, LDH, bone profile, bone marrow Prior to each cycle: Liver function tests and serum creatinine should be determined prior to initiation of therapy and prior to each treatment cycle. Complete blood counts should be performed prior to initiation of therapy and as needed to monitor response and toxicity, but at a minimum, prior to each treatment cycle. ASSESSMENT OF RESPONSE Haematological response, i.e. transfusion requirements, improvements in blood counts. Complete remission is not the ultimate objective of treatment. REVIEW BY CLINICIAN Prior to each cycle NURSE / PHARMACIST LED REVIEW Each cycle as applicable according to local practice. ADMINISTRATION NOTES Reconstituted azacitidine should be injected subcutaneously into the upper arm, thigh or abdomen. Injection sites should be rotated. New injections should be given at least 2.5 cm from the previous site and never into areas where the site is tender, bruised, red, or hardened. A new SC needle should be put onto the syringe after drawing up the drug and prior to administration. 25 gauge needle recommended. This needle should NOT be purged of air prior to injection being administered. Ensure adequate contraception will be used if appropriate Azacitadine has a short expiry once prepared, up to 8 hours if stored in the refrigerator (2 C to 8 C) immediately after reconstitution. If stored at room temperature it only had 45minutes expiry. Before administration the syringe filled with reconstituted suspension should be allowed up to 30 minutes prior to administration to reach a temperature of approximately 20 C 25 C. If the elapsed time is longer than 30 minutes, the product will have to be discarded. TOXICITIES Common: Myelosuppression, Grade 3 or 4; reaction at injection sites Less Common: Nausea, diarrhoea or constipation Azacitidine for treatment of Myelodysplastic Syndrome Page 2 of 6

3 DOSE MODIFICATION / TREATMENT DELAYS Haematological Toxicity: Haematological toxicity is defined as the lowest count reached in a given cycle (nadir) if platelets fall below 50x10 9 /l and/or absolute neutrophil count (ANC) below 1x10 9 /l. If haematological toxicity is observed following azacitidine treatment, the next cycle should be delayed until the platelet count and the ANC have recovered. Recovery is defined as an increase of cell line(s) where haematological toxicity was observed of at least half of the difference of nadir and the baseline count plus the nadir count. In order to satisfy the criteria for count recovery the recovered count must be greater than or equal to nadir count+ (baseline - nadir / 2) See Appendices 1 and 2 for guidance to adjust the dose of azacitidine according to haematological toxicity. Following dose modifications, the cycle duration should return to 28 days. Renal toxicity: If unexplained elevations in serum creatinine to 2-fold above baseline values and above ULN occur, the next cycle should be delayed until values return to normal or baseline and the dose should be reduced by 50 % on the next treatment cycle. TREATMENT LOCATION BCSH Level 1 4 Haematology Treatment Facilities REFERENCES: Summary of Product Characteristics, %20powder%20for%20suspension%20for%20injection/ Fenaux P et al (2009) Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study. The Lancet Oncology. 10(3) Azacitidine for treatment of Myelodysplastic Syndrome Page 3 of 6

4 APPENDIX 1 : DOSE ADJUSTMENT ALGORITHM FOR USE OF AZACITIDINE Baseline neutrophil 1.5x10 9 /l platelet 75x10 9 /l Baseline neutrophil < 1.5x10 9 /l platelet < 75x10 9 /l Azacitidine 75 mg/m (28 day cycle) See Appendix 2 14 d > 14 d Nadir neutrophil >1x10 9 /l platelets >50x10 9 /l Nadir neutrophil 1x10 9 /l platelets 50x10 9 /l Give 100% of previous dose Give 50% of previous dose The next cycle should be delayed until the platelet count and the neutrophil count have recovered. *Recovery = counts Nadir count + (0.5 x [Baseline count Nadir count]) Azacitidine for treatment of Myelodysplastic Syndrome Page 4 of 6

5 APPENDIX 2 : DOSE ADJUSTMENT ALGORITHM FOR USE OF AZACITIDINE IN PATIENTS WITH INITIAL LOW COUNTS Baseline neutrophil < 1.5x10 9 /l platelet < 75x10 9 /l Azacitidine 75 mg/m day cycle Fall in count s <50% of baseline Fall in count s >50% of baseline improvement in any cell line differentiation? YES NO 14 d > 14 d bone marrow examination cellularity > 50% cellularity 50% 21 d > 21 d cellularity 15-50% cellularity <15% Give 100% of previous dose Give 50% of previous dose Give 33% of previous dose The next cycle should be delayed until the platelet count and the neutrophil count have recovered. *Recovery = counts Nadir count + (0.5 x [Baseline count Nadir count]) Azacitidine for treatment of Myelodysplastic Syndrome Page 5 of 6

6 Document Control Document Title: Azacitdine for treatment of Myelodysplastic Syndrome Document No: Author: Approved by: CRP10H041 Due for Review: May 2016 Zor Maung, Haematology NSSG Chair Calum Polwart, Network Pharmacist NECN Current Version: 1.1 Reviewed by: Calum Polwart Date Reviewed: 28 May 2014 Summary of Changes 1.2 Reviewed. Formatted onto Area Team Document. No changes Azacitidine for treatment of Myelodysplastic Syndrome Page 6 of 6