Presentation (5).details description in chemotherapy

Adverse events after chemotherapy

1. COMMON TERMINOLOGY CRITERIA FOR ADVERSE EVENTS

2. IMMEDIATE Allergic
-Infusion related
-Anaphylactic
Pain at infusion site
-Irritant
-Vesicant
Urine discolouration -Doxorubicin
-Mitoxantrone

3. Nausea, vomiting Within few mins Peaks around 4-6 hours
Usually resolves around 24 hours

4. Within days Delayed onset emesis >24 hours upto 7 days Fatigue Myelosuppression Usually at nadir Mucositis Febrile neutropenia Diarrhea, constipation
Reduced appetite
Metallic taste

5. Within weeks Alopecia Cisplatin, doxorubicin Peripheral neuropathy Platins Dry skin, pigmentation
Nail changes
Ototoxicity (cisplatin)
Sterility Amenorrhoea Memory dysfunction
Cardiotoxicity

6. EMETOGENIC CHEMOTHERAPY

7. GRADING OF NEUTROPENIA Grade 1- ANC >1500 Grade 2-ANC 1000-1500 Grade 3-ANC 500- 1000 Grade 4- ANC < 500

8. NCCN RISK GROUP FOR Febrile neutropenia Low risk grp - < 10 % no any symptoms/ comorbidity No need of prophylaxis INTERMEDIATE RISK GRP – 10-20 % Prior Radiation therapy/chemotherapy Persistent neutropenia Tumor affecting BM Recent sx /open wound Liver failure Kidney failure Agr 65 or more and receiving chemotherapy

9. High risk inpatient status when fever developed have significant comorbidities or clinical instability had allogeneic stem-cell transplantation anticipated prolonged duration of severe neutropenia (ANC <100 for >7 days) renal (creatinine clearance <30 mL/min) or hepatic impairment (aspartate transaminase/alanine transaminase >5 times upper limit of normal) uncontrolled or progressive malignancy pneumonia or complex infection have grade 3-4 mucositis MASCC Risk Index score <21 or CISNE score >3

10. Since 1974, cytarabine is used either alone or in combination with an anthracycline (daunorubicin or idarubicin) in virtually all induction regimens for AML and as a component of consolidation and maintenance programs after remission .

11. short half-life and rapid plasmatic inactivation different schedules and dose-levels of cytarabine have been adopted for intravenous infusion low Standard high more recently- intermediate cytarabine doses most commonly used regimen -100 to 200 mg/m2/d for 5 to 7 days

12. high-dose 2 to 3 g/m2 every 12 h for up to six doses introduced about three decades ago, after the landmark CALGB study published in 1994 it became central to the improvement in the treatment of patients with AML . used primarily in the consolidation phase and upfront in patients with unfavorable, intrinsically drug resistant, oncogenic subtypes (8;21), inv16, del16, t(16;16) high-dose cytarabine has been the optimal post-remission therapy for patients with AML in first remission not proceeding to allogenic transplantation

13. The toxicity profile of cytarabine is highly dependent on the dose and schedule of administration. Leukopenia and thrombocytopenia occure - days 7 and 14 after drug administration. Gastrointestinal toxicity - mild-to-moderate mucositis and diarrhea . Occasionally acute pancreatitis has been reported in patients receiving cytarabine as a continuous infusion

14. Cytarabine syndrome occur within 12 h after the start of drug infusion with the onset of fever, myalgia, joint and bone pain, maculopapular rash, keratoconjunctivitis , and occasional chest pain
most likely represents an allergic reaction to cytarabine
patients usually develop symptoms months after the first dose,
corticosteroids resolve within 24 h when cytarabine is discontinued

15. high dose cytarabine 2 to 3 g/m2 with each dose common major side effects biphasic pancytopenia central nervous system toxicity, skin eruptions hyperbilirubinemia in > 10% of patients infection seizures

16. Acute cerebellar toxicity dysarthria with truncal and gait ataxia cerebral syndrome - encephalopathy, psychosis, seizures, and coma. widespread loss of Purkinje cells in the cerebellum . begins with somnolence and occasionally an encephalopathy develops two to five days after beginning treatment may also be delayed, occurring up to 3–8 days after treatment has begun. severe cerebellar toxicity - treatment discontinuation

17. neurotoxicity peripheral neuropathies resembling GBS , brachial plexopathy , lateral rectus palsy, optic neuropathy, or an extrapyramidal syndrome
Risk factor- cumulative cytarabine dose, prior CNS disease renal impairment high-dose therapy (>18 g/m2 per cycle) age >50 years

18. fatal cardiomyopathy - combination with cyclophosphamide Anaphylaxis - acute cardiopulmonary arrest GI toxicity - bowel necrosis and esophagus ulceration

19. Cytarabine lung Subacute respiratory failure Diffuse changes on chest radiographs Dx of exclusion

20. Occular toxicity excessive tearing, photophobia, burning ocular pain and blurred vision
o/e conjunctival injection central punctate corneal opacities with subepithelial granular deposits decreased visual acuity

21. HMAs MOA – hypomethylation of DNA Drugs Azacytidine Dacitabine Azacytidine 75 mg/m2 × 7 days Dacitabine 20 mg /m2 × 5 days Started with veneticlax on day 1 28-day cycles

22. Common side effects bone marrow suppression nausea, vomiting, diarrhea, stomatitis Bruising abdominal pain myalgias headache, dizziness, fatigue fever, rash and pruritus.

23. Uncommon but potentially severe adverse events severe myelosuppression febrile neutropenia Pneumonitis sepsis tumor-lysis syndrome embryo-fetal toxicity.

24. venetoclax BCL2 inhibitor BCL-2 overexpression has been implicated in survival of AML cells and treatment resistance  combination with AZA/  DAC) or low-dose cytarabine (LDAC) for the treatment of newly diagnosed AML in older patients (≥ 75 years) or in those with comorbidities precluding the use of intensive induction chemotherapy (DiNardo et al., 2020; Wei et al., 2020). 

25. Neutropenia In the case of grade 3 neutropenia with infection/fever or grade 4 neutropenia at first occurrence, venetoclax interruption is recommended until return to grade 1 or baseline level, followed by administration of venetoclax at its pre-interruption dose. For second/subsequent occurrences, venetoclax should be interrupted and subsequently resumed following dose-reduction guidelines

26. Management Remission status by bone marrow assessment should be considered to guide the management of neutropenia Grade 4 neutropenia (ANC < 500/ µL) –G-CSF and antimicrobial prophylaxis, can be used if clinically indicated for neutropenia

27. NAUSEA AND VOMITTING Gastrointestinal disorders are the prominent class of AES - venetoclax as a single agent or in combination studies. Antiematics metoclopramide Prochlorperazin dolasetron granisetron

28. Drug interactions