SUPPORTIVE CARE IN ONCOLOGY Jiří Šedo, Radka Obermannová, Ondřej Sláma Medical Oncology, Masaryk Memorial Cancer Institute Understanding….  Anti-cancer Therapy  Radiotherapy  Chemotherapy, Targeted treatment  Surgery  ….  Supportive Therapy  Management of cancer-related symptoms and complications  Management of the anti-cancer therapy side effects Case report  Young man, student, born 1995  Without comorbidities  Diagnosed with Superior Vena Cava Syndrom - autumn 2016 Superior Vena Cava Syndrom symptoms  Oedema (swelling due to excess fluid) of the face and arms,  Development of swollen collateral veins on the front of the chest wall,  Shortness of breath,  Difficulty of swallowing,  Headache, stridor, epiglottis, edema of the brain reported. Diagnosis  Metastatic high grade lung adenocarcinoma  Molecular analysis- ALK positive tumor  3-5%, usually younger patients Supportive treatment  Superior Vena Cava Syndrom- LMWH, corticosteroids, fluids, radiotherapy  antidepressants  Jewett spinal brace  Hypercalcaemia- bisphosphonates  Pain - analgetics (fentanyl, NSAI) Treatment trajectory Courtesy:J.Herrstedt Side-effects of the Anti-cancer Therapy  Common side-effects  Haematologic toxicity  Gastrointestinal toxicity  Specific side-effects  Nephrotoxicity  Urotoxicity  Cardiotoxicity  Neurotoxicity  Pneumotoxicity  Skin toxicity Adverse events of chemotherapy (Toxicity) Grading Grade 0 1 2 3 4 mild moderate severe Very severe/ Life-threatening Neutropenia Granulocytes >2.0 x 10*3 1.5 – 1.9 1.0 – 1.4 0.5 - 0.9 <0.5 Thrombocytopenia WN Plt x 10*3 75.0 - normal 50.0 – 74.9 25.0 – 49.5 <25 Anemia WNL Hgb 10.0 - normal 8,0 – 10,0 6,5 – 7,9 <6.5 Vommiting none 1 episode in 24 hours 2-5 episodes in 24 hours 2-5 episodes in 24 hours >10 episodes in 24 hrs or parenteral support Diarrhoea none increase of 2-3 stools/day 4-6 stools or nocturnal stools or moderate cramping 7 – 9 stooles or incontinence or severe crampting > 10 stools / day or grossly bloody diarrhea, or need of parenteral support Sensoric Neuropathy No or no change Mild parethesias, loss of deep tendon reflexes Mild or moderate objective sensory loss, moderate paresthesias Severe objecitve sensory loss or paresthesias that interfere with function Case report  V. M.  50 yeart old man treated for carcinoma of the urine bladder  Underwent radical cystectomy, 8 out of 14 lymph nodes positive  Undergoing adjuvant chemotherapy  Coming to our office 10 days after second cycle of chemotherapy cisplatin/gemcitabine V.M.  Fatigue, weakness  Temperatures of about 39°C with shivering yesterday  Black stool  Total loss of appetite, nausea, no vomiting V.M.  CBC:  Granulocytes: 0,3 x 10*9/l  Thrombocytes: 24, 000 x 10*6/l  Hb: 8.2g/dl  CRP: 130 mg/l  Creatinine: 145 µmol/l  Quick – INR: 1,35  Summary:  Febrile neutropenia  Thrombocytopenia with internal bleeding  Impaired kidney function(nephrotoxicity, dehydration) Grading Grade 0 1 2 3 4 mild moderate severe Very severe/ Life-threatening Neutropenia Granulocytes >2.0 x 10*3 1.5 – 1.9 1.0 – 1.4 0.5 - 0.9 <0.5 Thrombocytopenia WN Plt x 10*3 75.0 - normal 50.0 – 74.9 25.0 – 49.5 <25 Anemia WNL Hgb 10.0 - normal 8,0 – 10,0 6,5 – 7,9 <6.5 Vommiting none 1 episode in 24 hours 2-5 episodes in 24 hours 2-5 episodes in 24 hours >10 episodes in 24 hrs or parenteral support Diarrhoea none increase of 2-3 stools/day 4-6 stools or nocturnal stools or moderate cramping 7 – 9 stooles or incontinence or severe crampting > 10 stools / day or grossly bloody diarrhea, or need of parenteral support Sensoric Neuropathy No or no change Mild parethesias, loss of deep tendon reflexes Mild or moderate objective sensory loss, moderate paresthesias Severe objecitve sensory loss or paresthesias that interfere with function Leukopenia/Neutropenia  Most-significant and frequently limiting side effect of CHT  Nearly always dose-dependent  Nearly all conventional cytostatics can cause neutropenia – level depends on dose  Maximal drop-off expect 7-10 days after initiation of the new cycle Scales Safety Dose - intensity Febrile neutropenia  Definition:  1x axillary temperature 38,3°C or 38°C lasting more than 1 hour  Neutropenia < 0.5 x 10*9/l or < 1.0x10*9/l and predicted decline  Always serious condition  High mortality especially among high-risk patients (14 - 36%)  can be substantially decreased by appropriate management! CAVE: corticosteroids can mitigate symptoms of infection Febrile Neutropenia: Initial Examination  PE  CBC, basic chemistry, CRP, coagulation, urinalysis  Elective: Ig quanity, flow-cytometry  Imaging:  Chest X-ray etc.  Microbiology  Blood cultures 2x2  Urine  Elective: Catheters, stool, throat culture Febrile Neutropenia Stratification and ATB therapy Febrile Neutropenia: Therapy  ATB  Do not wait!  Use combinations of ATB!  Isolation  Vital functions monitoring  If case of sepsis/SIRS  ICU monitoring  Consider G-CSF therapy  Specific recommendations for ATB therapy G-CSF  granulocyte colony-stimulating factor  Filgrastim, …  Also available in PEGylated form  Indications:  Prophylaxis of febrile neutropenia  Treatment of FN Thrombocytopenia  One subgroup of myelotoxicity  Risk of bleeding  Which organs can be affected?  CAVE: brain meta, tumors in GI or GU tract!  What is the only way of management?  Thrombopoietic Growth Factors – not effective, not available  Thrombocyte substitution – indications varies (donors + $$)  In case of bleeding and platelets bellow 20x109/l ??  Platelets below 10x109/l in asymptomatic pacient? Anaemia  Usually not as a toxicity of chemotherapy  Cancer patients:  Anaemia of chronic disease – redistribution of Fe accompanying malignancy itself  Post-hemorrhagic anaemia  bleeding tumors of GI and GU tract, …  CAVE: thrombocytopenia  Other: deficiencies of B12, iron, folic acid, malnutrition, renal failure, chemotherapy …. Management of anaemia  Substitution of deficiencies if identified: folate, B12, Fe (not in case of redistribution!)  Blood transfusion + fast correction (1 item - increase approx. Hb 10 g/l) - general transfusion risks  Erytropoetin (EPO) - Controversies persist …. - Slow increase in Hb per 10 g/l in 4 weeks GASTRO-INTESTINAL TOXICITY Nausea and vomitting Diarrhea Mucosal toxicity (mucositis, malabsobtion) Nausea / vomiting . . .  Definition  Nausea is an unpleasant subjective sensation of being about to vomit.  Vomiting is the reflex expulsion of gastric contents through the mouth . . . Nausea / vomiting  Impact very distressing:  Awareness of nausea  Inability to keep food or fluids down  malnutrition, dehydration  Acid and bitter tastes  Unpleasant smells of vomitus Pathophysiology Pathophysiology  Nausea  Vomiting  Neuromuscular reflex Case – D. J.  48 years old woman with metastatic lung cancer  METS in both lungs, liver, adrenal glands, bones  Without any signs of disease!  Treated by chemotherapy cisplatin/etoposide  What will you ask the patient ?? Assessment  When?  Intermittent or constant?  Associated with sights or smells?  Eating patterns?  Bowel patterns?  Medications? Level of emetogenicity Minimal (<10%) Bleomycin Vinblastine Vincristine Methotrexate Low (10-30%) Capecitabine(Xeloda) Docetaxel Etoposide Gemcitabine Paclitaxel Mild (30-60%) Irinotecan Ifosfamide Moderate (80-90%) Carboplatin Doxorubicinn High (>90%) Carmustine Cisplatin Cyclophosphamide Dacarbazine Stimulation of CTZ  anti-D2: metoclopramide 10mg q8h triethylperazine 6,5mg q8h EPS (especially combination with AD) haloperidol 0.5mg-1mg q6-12h prochlorperazin(Compazine): 10mg q6-8h  anti 5-HT3:  setrons:  ondasetron , granisetron(Zofran): 8mg q8h  palonosetron, ….  next generation antipsychotics  olanzapine (Zyprexa) Chemotherapy induced nausea  Neurokinin-1 antagonist  Aprepitant , netupitant  Corticosteroids  Dexamethasone 8mg i.v./p.o. daily  Anticipation nausea  Benzodiazepines: alprazolam 0,25mg-0,5mg q8h bromazepam 1,5mg q8h  Other emetogenic drugs Opioids, digoxin, antibiotics, iron supplementation Chemotherapy-induced nausea  Acute  <24 hours  Chemoreceptor trigger zone  Serotonin release in the gut  Delayed  Unclear mechanism D.J. management  Premedication:  Dexamethasone 8mg i.v. 1-0-0 during CHT  Netupitant/palonosetron 1x before CHT  Olanzapine 5mg tbl. 1-0-0 during CHT  At home:  Dexamethasone 4mg 1-0-0 for 3days  Omeprazol 20mg 1-0-0  PRN: Olanzapine 1x daily If not working?  Alprazolam 0,5mg tbl. before and during CT q8h – for anticipation nausea A.S.  56 years old woman with breast cancer, multiple bone MTS  Underwent 1st line chemotherapy last course 3weeks ago Effect: progression in bones  5 days ago started feeling nauseated, vomitting 3xD  Headache  Loss of conciousness – fall, injury  Comming to you …. A.S.  She had a good appetite generally  She used to throw up when she had finished her meal  Now, she feels nauseated again - what medication should we use? Dexamethasone 8mg /100ml saline i.v. 20minutes infusion q8h + Manitol 20% 200ml i.v. inf. Q8h CT: multiple MTS in brain with collateral oedema  60 years old man with carcinoma of the urether  Resection of the right urether and nephrectomy  Recurrence in retroperitoneal nodes and right pelvis  Retroperitoneal lymph node dissection and resection of the tumor masses in right pelvis. - incidental transsection of the right nervus obturatorius  After surgery he suffered from pain deep in the right inguina which irradiated to his right limb.  MRI 6/2010: mass 3x5cm in the right pelvis close to the the plexus sacroiliacus  Already relatively high doses of opiates V.B. V.B.  8/2010 Patient comming to our office: Total loss of appetite, loosing weight, Nausea not frequently weak, sleeping whole day, constipation 4days without stool, …. What are the possible causes of nausea? - Opioids - Bowel obstruction, hypomotility, constipation V.B. Our medication: haloperidol 1mg q8h Mucosal toxicity and diarrhea  Oral mucositis  Diarrhea Diarrhea  frequency + consistency Treatment:  Rehydratation, ion substitution  Dietary changes, Management of intestinal dysmicrobia  Total parenteral nutrition in severe cases  Diosmecticum (Smecta)  Loperamide and other derivates active on opioid- receptors  Octeotride (somatostatin analog) Mucositis Mucositis - management  hygiene of oral cavity including oral antiseptics (chlorhexidin, local corticosteroids…)  Diet changes  Analgesics - orally preferred  Realimentation (incl. parenteral nutrition) Specific toxicity  Nephrotoxicity  Urotoxicity  Cardiotoxicity  Neurotoxicity  Pneumotoxicity  Skin toxicity Nephrotoxicity  Toxicity of cytostatics Cisplatin most frequently (carboplatin or oxaliplatin not) Prevention: massive hydration + forced diuresis (Manitol)  Hyperuricaemia as a part of tumor lysis syndrome Prevention:  Hydratation  Initial dose reduction  Rasburicase  Bicarbonate historically Urotoxicity  Heamorhagic cystitis  Cyclophosphamide, Ifosfamide  Prevention  adequate fluid intake  Mesna (assists to detoxify toxic metabolite acrolein by reaction of its sulfhydryl group) Cardiotoxicity  Cardiomyopathy  Anthracyclines Doxorubicin=adriamycin, Epirubicin – use in breast cancer  CAVE: irreversible heart failure!!!  Targeted therapy Trastuzumab(Herceptin) – in breast cancer  Usually reversible  Dysrythmias (anthracyclines, paclitaxel)  Spasms of coronary arteries (5-fluorouracil) Neurotoxicity  Peripheral neuropathy Paclitaxel, oxaliplatin, ....  very frequent and often limiting toxicity  Symptoms:  Impaired sensitivity  Paresthesia  Neuropathic pain  Reversible/irreversible (cumulative dose principle)  Treatment – not very effective (antiepileptics)  Bowel motility  Paralytic ileus Pneumotoxicity Bleomycin  Character of Pneumonitis/fibrosis/bronchospasms  Prevention  Cumulative dose principle  Avoid in patients with pulmonary restriction or obstruction  Treatment very limited Skin toxicity  Allopecia  Hand-and-foot syndrome by 5-fluorouracil  Specific skin changes after targeted therapy  Acne-like rash after cetuximab (colorectal, H&N)  Variable skin rash after erlotinib (NSCLC) - correlation between the severity of the skin reactions and increased survival  Para-venous application of chemotherapeutics  necrosis after doxorubicin,  flebitis after 5-fluorouracil Hand-foot syndrom sorafenib, sunitinib, capecitabin EGFR antibodies, inhibitors EGFR antibodies EGFR antibodies RTx and EGFR Ab Side effects of Immunotherapy Checkpoint inhibitors Side effects of Immune Checkpoint inhibitors - management Conclusions…  Effective management of side effects of anticancer therapy is a key to success  Thank you for your attention!