Management of common chemotherapy related side effects. Dr Lee-Ann Jones

Transcription

1 Management of common chemotherapy related side effects Dr Lee-Ann Jones

2 Deciphering oncology terms treatment intent

3 Chemotherapy terms / intents Adjuvant chemotherapy - Chemotherapy given to destroy residual/ microscopic tumour cells that may be present after the known tumour is removed by surgery. Adjuvant chemotherapy is given to prevent a possible cancer recurrence. Neoadjuvant chemotherapy - Chemotherapy given prior to the surgical procedure. Neoadjuvant chemotherapy may be given to attempt to shrink the cancer so that the surgical procedure may not need to be as extensive.

4 First line chemotherapy - Chemotherapy that has, through research studies and clinical trials, been determined to have the best probability of treating a given cancer. Can be referred to as standard therapy. Aim could be to cure or improve survival. Second line chemotherapy - Chemotherapy that is given if a disease has not responded or reoccurred after first line chemotherapy. In some cases, this may also be referred to as salvage therapy. Palliative chemotherapy - Palliative chemotherapy is given specifically to prolong survival or control symptoms.

5 Acute leukaemia: Induction chemotherapy - Chemotherapy given to induce a remission. Consolidation chemotherapy - Chemotherapy given once a remission is achieved. The goal of this therapy is to sustain a remission. Consolidation chemotherapy may also be called intensification therapy. Maintenance chemotherapy - Chemotherapy given in lower doses to assist in prolonging a remission. Maintenance chemotherapy is used only for certain types of cancer, most commonly acute lymphocytic leukaemia and acute promyelocytic leukaemia.

6 Side effects of treatment

7 health/cancer/effects-on-body

8 Distinguishing the inconvenient side effects from the life threatening

9 Common acute side effects Myelosuppression: Neutropaenia Gastro-intestinal: Nausea and Vomiting Mucositis Diarrhoea

10 1. Neutropaenic fever Effects of Chemotherapy: Bone marrow suppression decrease in circulating neutrophils Mucosal damage gut or mouth Decreased immunity and lack of integrity of mucosal membranes allows invasive infection by colonising bacteria or fungi Patient education Clinical suspicion

11 Definition of neutropaenic fever Neutropaenia: Absolute Neutrophil Count <500 cells/microl. (0.5) Typically days post chemotherapy Fever in neutropenic patients is defined as: a single oral temperature of 38.3 C or a temperature of 38 C sustained over a one-hour period

12 Presentation Non-specific Fever Often no local signs of infection inflammatory response lacking

13 Risk factors for developing neutropaenic fever 1. Patient Age (>65 yrs) Female High body surface area Poor PS (medical co-morbidities) Poor nutritional status 2. Disease Elevated LDH Advanced disease Bone marrow failure due to involvement 3. Treatment Chemo regimen / Dose dense regimens Failure to use prophylactic growth factors

14 Risk assessment of developing serious complications Low risk: Expected to have ANC of < 0.5 for < 7days No significant co-morbidities Good PS High risk: ANC of <0.5 expected to continue for >7 days Presence of significant co-morbidities

15 Comorbid medical problems, including, but not limited to: Hemodynamic instability Oral or gastrointestinal mucositis Gastrointestinal symptoms, including abdominal pain, nausea and vomiting, or diarrhoea Neurologic or mental status changes of new onset Intravascular catheter infection New pulmonary infiltrate or hypoxia Underlying chronic lung disease Complex infection at the time of presentation Renal or hepatic insufficiency Alemtuzumab use within the past two months Uncontrolled cancer Inpatient status at the time of development of fever

16 Investigation FBC and Differential count Confirmed neutropaenia: Blood culture Commence Renal / liver function empiric CRP antibiotics CXR if respiratory symptoms Routine cultures from asymptomatic sites Risk assessment Commence G-CSF: filgastrim (Neupogen)

17 Which antibiotic? Broad spectrum monotherapy 3 rd or 4 th generation cephalosporin or penem e.g.: Cefepime 2 g IV every eight hours Meropenem 1 g IV every eight hours Amend to appropriate antibiotic if organism identified.

18 Which organism? No organism identified in majority if cases Bacteria are the most frequent infectious causes Gram positive: Gram negative = 60:40 Gram-negative bacteria generally associated with the most serious infections. S. epidermidis is the most common gram-positive pathogen, accounting for approx. one half of all gram-positive infections. Fungi associated with persistent or recurrent fever.

19 Prevention G-CSF: Primary prophylaxis: recommended in cases where risk of febrile neutropaenia exceeds 20% Secondary prophylaxis: use of G-CSF with subsequent chemotherapy cycles where previous neutropaenia documented. Non-curative setting: dose reduce

20 2. Chemotherapy Induced Nausea and Vomiting (CINV) Nausea remains one of the most distressing side effects of chemotherapy Preventable in 70-80% of cases Anti-emetic guidelines: MASCC ESMO 2016* Emetogenic potential of chemotherapy agents: High (>90%) Moderate (30-90%) Low (10-30%) Minimal (<10%) *Annals of Oncology 27 (Supplement 5): v119 v133, 201doi: /annonc/mdw27

21 4 categories of CINV Acute onset: (mostly serotonin related), occurring within 24 hours of initial administration of chemotherapy Delayed onset:(in part substance P related), occurring 24 hours to several days after initial treatment Anticipatory: observed in patients whose emetic episodes are triggered by taste, odour sight, thoughts, or anxiety secondary to a history of poor response to antiemetic agents or inadequate antiemetic prophylaxis in the previous cycle of chemotherapy Breakthrough CINV is defined as an event that happens in spite of optimal preventive treatment.

22 Anti-emetic classes Serotonin Receptor (5-HT3) Antagonists Corticosteroids NK1 Receptor Antagonist

23 Anti-emetic doses

24 Polypharmacy: the practice of administering many different medicines concurrently for the treatment of a single disease

25 Breakthrough nausea & vomiting If optimal therapy is used as prophylaxis, then repeated dosing of the same agents is unlikely to be successful. Consider: Dopamine-receptor antagonists (metoclopramide) Benzodiazepines (lorazepam) Neuroleptics (olanzapine 2.5-5mg od) Cannabinoids

26 Typical script

27 3. Oral mucositis Mucositis is the most common oral toxicity of chemotherapy (others: xerostomia, change in taste, gingival bleeding) Affects 20-40% of standard dose chemotherapy patients Loss of mucosal integrity painful ulceration and allows bacterial colonization Starts shortly after chemo administration and peaks at day 7 Range: mild symptoms to severe erosive mucositis with inability to eat or drink Severity dependant on type of chemotherapy

28 Problem Breakdown of the mucosal barrier predisposes to superinfection, which may remain localized or become disseminated, particularly if neutropaenia is present. Pain may limit the ability to take in adequate fluids and nutrition.

29 Treatment is supportive and mainly aimed at symptom control: Salt and baking soda mouthwash Soft diet avoid salt, acidic or dry foods Wipe mouth/ dentures after meal IV support if oral intake not possible Analgesics (topical or systemic) Anti-fungal treatment if superinfection with candida suspected Consider possibility of viral superinfection intraoral blisters or unusually painful lesions

30 4. Diarrhoea Chemotherapy: Flouropyrimidines (5FU, capecitabine) Irinotecan Molecular agents: TKIs Anti-angiogenesis therapy: bevacizumab Immunotherapy: Ipilimumab Pembrolizumab / nivolumab

31 Mechanisms Chemotherapy induced diarrhoea: Secretory diarrhoea: chemotherapy induced epithelial damage Osmotic diarrhoea: increased intraluminal osmotic substances Altered gastro-intestinal motility Immunotherapy induced diarrhoea: Immune mediated enterocolitis

32 Grading Grade Diarrhoea 1 Increase of <4 stools per day over baseline; mild increase in colostomy output compared to baseline 2 Increase of 4-6 stools per day over baseline; moderate increase in ostomy output compared to baseline 3 Increase of >=7 stools per day over baseline; incontinence; hospitalization indicated; severe increase in ostomy output compared to baseline; limiting self care ADL 4 Life-threatening consequences; urgent intervention indicated 5 Death

33 Assessment History: Diet Other drugs (PPI, NSAID, metoclopramide, laxatives) Examination: assess for dehydration and sepsis Investigation: FBC, renal function, Mg 2+ Grade 3: blood and stool culture, C.difficle

34 Management Complicated CRD: grade 3-4 diarrhoea moderate to severe abdominal cramping Grade 2 or worse N &V declined PS Fever, sepsis, neutropaenia Bleeding Dehydration. Aggressive management: IV fluids, antibiotics, monitoring of electrolytes, octreotide

35 Uncomplicated CRD: Grade 1-2 (or grade 3 with no worrisome signs) Conservative management at home Oral rehydration Loperamide: 4mg stat, 2mg after each loose stool or 4 times per day After hours: can increase to 2mg every 2 hours Re-assess if persists beyond 24 hours or if worrisome features develop

36 Immunotherapy induced colitis Grade 1 & 2 diarrhoea: treat as for uncomplicated CRD. Add single dose of budesonide 9mg in grade 2 Grade 3 & 4 diarrhoea: IV steroids Methylprednisolone 125mg IV stat Oral prednisone 1-2mg/kg daily (taper over 4-8weeks) IV fluids Monitor electrolytes Watch for GIT complications perforation No improvement in hours: infliximab 5mg/kg every 2 weeks

37 Loeb's Rules of Therapeutics 1. If what you are doing is doing good, keep doing it. 2. If what you are doing is not doing good, stop doing it. 3. If you do not know what to do, do nothing. 4. Never make the treatment worse than the disease. Robert Frederick Loeb MD