Fluorouracil (5FU), epirubicin and cyclophosphamide
Magnesium deficiency is frequently associated with hypokalemia. Concomitant magnesium deficiency aggravates hypokalemia and renders it refractory to treatment by potassium. Herein is reviewed literature suggesting that magnesium deficiency exacerbates potassium wasting by increasing distal potassium secretion. A decrease in intracellular magnesium, caused by magnesium deficiency, releases the magnesium-mediated inhibition of ROMK channels and increases potassium secretion. Magnesium deficiency alone, however, does not necessarily cause hypokalemia. An increase in distal sodium delivery or elevated aldosterone levels may be required for exacerbating potassium wasting in magnesium deficiency. http://jasn.asnjournals.org/content/18/10/2649.abstract
Four classes of drugs are commonly used to treat CINV: corticosteroids, dopamine antagonists, serotonin antagonists, and NK-1 receptor antagonists.Corticosteroids and 5-HT3 receptor antagonists, alone or in combination, are recommended for treatment of acute CINV.The newest class of drugs approved to treat CINV is the NK-1 receptor antagonist.
Case 147 F - Metastatic Breast Ca Triage Fatigue, poor oral intake, fever, Breast Ca,Comments had chemo 6 days ago Breast Ca – 2005, L mastectomy (ER/PR+, Her2-,Background T1N1M0) FEC #6. Axillary recurrence 2008Sx excision XRT+TC Bone + liver mets- Jan 2012, May 2012 XRT L/spine, On palliative paclitaxel weekly. Fatigue, LOA, felt feverish, nausea, diarrhea,Presentation rest of ROS -ve
Are we worried about this patient ? • Why ? – Cancer itself is a serious condition – Metastatic disease – affecting multiple organ systems – Recent chemotherapy – immunosuppression
Approach to management • Basics – – Vitals (SBP 95, PR 90, T 37.8) • Examination – – Systemic Ex – NAD including PICC site in right arm • While assessing the patient – vomited once, had a loose BM, says now “feels hot” ! – Repeat vitals (SBP 90, PR 99, T 38.2)
Approach to management What next ? • Bloods – – FBC & routine bloods, C/S 2 Sets inc PICC, – CXR, urine m/c/s, ?sputum, stool m/c/s + CD toxin • Medications – – IV Tazocin, IV Ondanseteron, NS, Paracetamol, – ? Antidiarrheals (Toxic megacolon if CD+ve)
FBC is available WBC = 2 , ANC=0.6, (Hb 96, PLT 112) What does this mean ? Grade 3 Neutropenia - Referred to Oncology/ Medical team Grade 1 Grade 2 Grade 3 Grade 4 ANC 1.5-2 1-1.5 0.5-1 <0.5
Febrile Neutropenia • Febrile neutropenia exists when a patient with a neutrophil count less than 1.0x109/L has a temperature > 380 C, or if a patient is systemically unwell with a clinical suspicion of sepsis. • The major complication of febrile neutropenia is septic shock and treatment is directed at preventing the development of this complication. Early recognition of septic shock is essential to patient survival.
High Risk Patients – Active cancer + • Haematological malignancy • Myelosuppresive chemotherapy • Concurrent chemotherapy and radiotherapy • Age >60 • Co-morbidities eg. Diabetes, poor nutritional status. • Bone marrow involvement of cancer • Delayed surgical healing or open wounds • Unwell (eg hypotensive, oliguric) • On steroid dose >25mg prednisolone daily • Rapidly falling neutrophil count • History of neutropenia • Recent hospitalisation for infection
Assessment Careful history and physical examination including: • Type of cancer and recent treatment. • Vitals • Physical exam focusing on: Chest, Mucous membranes, Skin, Venous access devices, Peri-anal area, Urinary tract, Gastrointestinal Tract • Signs of infection may be subtle or absent as neutropenic patients may exhibit little or no inflammatory response
Differential diagnoses • Tumor fever – Progression of the underlying malignancy can be associated with tissue necrosis and inflammation that can yield low-grade or high fevers that do not improve with antibiotics. Patients with hematological malignancies often present with diurnal fevers. • Drug fevers – Drug fevers are typically high fevers that are often cyclical in nature. – Drug fevers may be associated with an eosinophilia, acute interstitial nephritis, or drug-induced hepatitis. – They should improve with discontinuation of the offending agent.
Differential diagnoses • Thromboembolism – Malignancy is a risk factor for thrombosis, which can cause fever. – Signs or symptoms of a deep vein thrombosis with extremity pain, erythema, or swelling may be present. – Additionally, signs or symptoms of a pulmonary embolism may be present with shortness of breath, tachycardia, chest pain, hypoxaemia, and cerebral embolism with new neurological signs or symptoms. • Paraneoplatic syndromes – Many malignancies are associated with the development of paraneoplastic syndromes, which are characterised by the development of auto-antibodies, presumed to have developed in response to tumour antigens. The resultant syndromes can mimic the known autoimmune syndromes. In addition, there are a number of paraneoplastic syndromes that affect the nervous system and are well characterised and associated with particular underlying malignancies.
Important to remember • Chemotherapy patients who present with a fever greater than 38’ C will be assumed to be neutropenic unless there is a white cell count within the previous 24 hours to the contrary. • Patients three months or less after a bone marrow transplant will be considered to be equivalent to a neutropenic patient in risk and treated accordingly independent of the neutrophil count.
Initial Investigations • Blood tests: FBE,EUC,LFT, Coags, CRP • Peripheral & Central line blood cultures (if patient has a central venous access device) NB. Do not flush central venous access device before withdrawal of blood for blood cultures, Do not discard initial blood specimen when taking blood from central venous access devices for blood cultures, use initial sample for blood culture • Mid stream urine sample • Sputum for M/C/S if patient has a productive cough • Faeces for M/C/S and Clostridium difficile toxin if there is diarrhoea • Swab all wounds, recent IVC site, central venous access sites • Chest x-ray
Antibiotic therapy • As early as possible, after blood cultures have been collected • Tazocin (piperacillin & tazobactam/piptazo) 4.5 g Q6H • ? Vancomycin • ? Antifungal • Discuss with oncology / medical teams
Few more points to remember • Neutropenic precautions/ Neutropenic diet • Good hygiene • Handwashing ! • Limit visitors • NO PR exam, PR medications • NO IDC
Case 261 M – Colorectal Ca Triage High stoma output, nausea, vomiting, poorComments oral intake CRC, s/p AR adj IV chemo, currently onBackground Capecitabine, also taking lactulose and senna High stoma output, 10-12 times previous twoPresentation days, Vomited X5, fatigue
Approach to management What next ? • Bloods – – FBC, EUC • Medications – – IV fluids – IV antiemetics • Blood Investigations – Cr 340, K+ 2.6
ARF with hypokalemia IV Fluids, potassium replacement • Repeat EUC in 12 hours • Cr 145, K+ 3.2, • Mg 0.58 is this significant ? Magnesium was corrected, • 36 hrs later K+ 3.6, Cr 105
Chemotherapy induced nausea & vomiting • CINV is a common adverse event associated with cancer treatment. • Up to 80% of patients undergoing chemotherapy experience nausea and vomiting. • The desire to avoid nausea and vomiting is so strong that patients have postponed or even refused treatment. • Additionally, CINV can impose limitations on the patient’s ability to function socially, maintain employment, or complete daily activities.
Pharmacologic agents • Corticosteroids – Dexamethasone, higher doses • Dopamine antagonists - Maxalon • Serotonin (5-HT3) antagonists – Ondansetron • NK-1 receptor antagonists – Aprepitant (Emend) - Selective antagonist of the binding of Substance P to the neurokinin 1 (NK1) receptor (125 mg PO day 1, 80 mg PO days 2-3)
Case 377 F – Recently Dx NSCLC, awaiting full staging Triage Headache, N/V severe in morning, newly DxComments lung Ca NSCLC, staging not done yet. Heavy smoker, noBackground other cormorbities. Headaches, N/V worse in mornings and withPresentation laughing, coughing, sneezing and straining, drowsy for 2 days
Management • IV dexamethasone 16 mg with PPi • Consider IV mannitol if not responding Further management, • Complete staging • Neurosurgical – Stereotactic Bx/ Cranitomy and resection • Ventricular shunts • Systemic chemotherapy
Case 447 M –Malignant Pheochromycytoma, liver/ bone mets Triage Unable to walk, LL numbness, BNO 2 daysComments Malignant Pheochromycytoma, liver/ bone metsBackground S/P resection of primary – right adrenal, followed by chemo 3 months ago Progressive LL weakness x 5-6 days, nowPresentation unable to walk at all, a/w numbness over B/L LL, Back pain, Denies HI /recent trauma BNO x 2 days ARU X1 day
Assessment • Vital Signs – T 38, PR 100, BP 95/55 • Back Pain 6/10 • Symmetrical B/L LL weakness, hyperreflexia, sensory impairment B/L LL • Rest of systemic examination - NAD
Whats going on ? • Septic screen – negative • Fever - ? Tumor fever • Neurological symptoms – MRI Extensive skeletal metastasis Extradural soft tissue component cause severe canal narrowing and cord compression at T6, T7 and T10 levels
Malignant spinal cord compression Grading score of MSCC Grade Severity 0 Involvement of the vertebral body without epidural space 1 Subarachnoid space impingement with no spinal cord deformation 2 Obliterated subarachnoid space and spinal cord deformation 3 Spinal cord deformation with no cerebrospinal seen
MSCC – Red flags • Pain –lower back pain, worse on recumbent position • Motor - May be hyperreflexic below the lesion and have extensor plantars • Sensory – ascending numbness and parasthesias • Bladder/ bowel involvement – Usually late, autonomic neuropathy presents usually as urinary retension
Management • IDC • Dexamaehtasone 8 mg TDS • Angioembolisation of vertebral tumour • T6 and T7 decompression corpectomy and fusion • Tolerated procedure well with post op Hb of 98 • Sent to HDU for closer monitoring • Well and stable, sent to general WD - POD 5 • Later on had a course of RT to T10
Case 557F – Newly diagnosed DLBCL Triage Requested admission for staging and cycle 1 ofComments RCHOP HTN, Newly Dx DLBCLBackground No specific complaints on admission, exceptPresentation some LN+
Management • CT – T/A/P • PET CT • BM • 2DECHO • Hydration and Allopurinol prior to chemotherapy • Then proceeded with chemotherapy • Why hydration and allopurinol ?
Tumor lysis syndrome • Metabolic derangements caused by the massive and abrupt release of cellular components into blood after rapid lysis of malignant cells. • ↑phosphate, ↑K, ↑uric acid, ↓Ca • Uric acid crystals/ Ca/ PO4 in renal tubules impaired renal function, ARF, even death • ↑phosphate leads to ↓Ca tetany, seizures, arrhythmia • ↑K life-threatening arrhythmia
High risk patients • High tumor cell proliferation rate, large tumor burden, tumor chemosensitivity • ALL, AML, NHL, Burkitt’s Lymphoma (heme malignancies) >>>Small cell >> Hodgkin’s disease, Multiple Myeloma, >Solid Tumors ( breast, GI, prostate etc.) • Signs and Symptoms are non-specific - Can occur before chemo, but usually within 12 to 72hrs after starting chemo
Management • “The best management is prevention.” • FLUIDS and HYDRATION – Aggressive hydration and diuresis – Improve intravascular volume, renal blood flow, GFR (decrease [solute] in distal nephron/renal microcirculation) – +/- diuretics (contraindicated in hypovolemia and obstructed uropathy)
Allopurinol• Competitive inhibitor of xanthine oxidase which decreases conversion of purine metabolites to uric acid. Used prophylactically for TLS• Prophylactic option for patients with a risk of TLS
References1. Clostridium difficile diarrhea induced by cancer chemotherapy www.Archinte.Jamanetwork.Com/article.Aspx?Articleid=6165562. Loperamide related toxic megacolon in clostridium difficile colitis. www.Ncbi.Nlm.Nih.Gov/pmc/articles/pmc2429653/3. Common toxicity criteria (ctc) www.Eortc.Be/services/doc/ctc/ctcv20_4-30-992.Pdf4. Febrile neutropenia management guidelines www.Gha.Net.Au/uploadlibrary/394074071febrile_neutropenia_management_guidelines0210.Pdf5. Mechanism of hypokalemia in magnesium deficiency www.jasn.Asnjournals.Org/content/18/10/2649.Abstract6. Antiemetics: american society of clinical oncology clinical practice guideline update www.Asco.Org/ascov2/practice+%26+guidelines/guidelines/clinical+practice+guidelines/antiemetics%3a+ american+society+of+clinical+oncology+clinical+practice+guideline+update7. Brain metastases www.aans.org/Patient%20Information/Conditions%20and%20Treatments/Brain%20Metastasis.aspx8. Emergency treatment of malignant extradural spinal cord compression: an evidence-based guideline. www.jco.ascopubs.org/content/16/4/1613.full.pdf9. The Tumor Lysis Syndrome www.nejm.org/doi/full/10.1056/NEJMra090456910. Allopurinol www.nlm.nih.gov/medlineplus/druginfo/meds/a682673.html