Systemic management of pancreatic cancer: Supportive care

Transcription

1 Systemic management of pancreatic cancer: Supportive care Snežana Institute for Oncology and Radiology of Serbia Serbia, Belgrade

2 Supportive Care in Cancer The prevention & management of the adverse effects of cancer and its treatment From early detection through diagnosis, treatment, survivorship or palliative care & End of life care Supporting patients & families to maximize the QoL despite cancer & its treatment Multiple dimensions of support

3 Pancreatic Cancer : Supportive care guidelines (ESMO) Cancer pain Nausea and vomiting Oral and GI mucositis (diarrhea) Febrile neutropenia Hematopoietic growth factors Chemotherapy induced peripheral neuropathy (CIPN) (ASCO, 2014) Chemotherapy extravasation Venous thromboembolism

4 FOLFIRINOX vs Gemcitabine: AEs Grade 3/4 AE, % Hematologic FOLFIRINOX (n = 171) Gemcitabine (n = 171) P Value Neutropenia <.001 Febrile neutropenia 5.4%* Thrombocytopenia Nonhematologic Fatigue NS Vomiting NS Diarrhea <.001 Sensory neuropathy <.001 Elevated ALT <.001 * 42.5% of pts w/ GCSF Conroy T, et al. N Engl J Med. 2011;364: Slide credit: clinicaloptions.com

5 MPACT: Gemcitabine ± Nab-Paclitaxel AEs Event Gem + Nab-P (n = 421) Gem Only (n = 402) AE leading to death 4 4 Hematolgic AEs grade 3 Neutropenia 38% 27% Leukopenia 31 % 16 % Thrombocytopenia 13 % 9 % Anemia 13 % 12 % Receipt of growth factors 26 % 15 % Febrile neutropenia 3 % 1 % Nonhematologic AEs grade 3* Fatigue 17 % 7 % Peripheral neuropathy 17 % 1 % Diarrhea 6 % 1 % * 5% of pts. Von Hoff DD, et al. N Engl J Med. 2013;369: Slide credit: clinicaloptions.com

6 Chemotherapy induced nausea and vomiting (CINV) The risk for CINV: FOLFIRINOX: moderate Gemcitabine: low Gem+ Nab-Paclitaxel: low Supportive Care Goal: Prevention and control of CINV after CHT (0-120h)

7 Management of CINV (MASCC / ESMO) Emetogenicity of the regimen FOLFIRINOX: Moderately emetogenic (determined by oxaliplatin, irinotecan) Oxaliplatin & irinotecan: different potential for delayed emesis Gem+ Nab-Paclitaxel: low emetic risk Patient risk factors for CINV Increased risk Female gender Younger age Morning sickness Anxiety Chemotherapy-naïve Alcohol abuse Decreased risk Disease-related symptoms & concomitant medications DEX, dexamethasone.

8 2016 V.1.1 EMETIC RISK GROUP High Non-AC High AC Carboplatin Moderate (other than carboplatin) Low Minimal 5-HT 3 = serotonin 3 receptor antagonist ANTIEMETIC GUIDELINES: MASCC/ESMO ACUTE Nausea and Vomiting: SUMMARY DEX = dexamethasone ANTIEMETICS HT 3 DEX NK HT 3 DEX NK HT 3 DEX NK 1 5-HT 3 + or DEX or 5-HT 3 DEX DOP No routine prophylaxis NK 1 = neurokinin 1 receptor antagonist such as aprepitant or fosaprepitant or rolapitant or NEPA (combination of netupitant and palonosetron) DOP = dopamine receptor antagonist NOTE: If the NK 1 receptor antagonist is not available for AC chemotherapy, palonosetron is the preferred 5-HT 3 receptor antagonist.

9 2016 V.1.1 EMETIC RISK GROUP ANTIEMETIC GUIDELINES: MASCC/ESMO ANTIEMETICS High Non-AC DEX or ( if APR 125mg for acute: ( MCP + DEX ) or APR ) High AC None or ( if APR 125mg for acute: DEX or APR ) Carboplatin None or ( if APR 125mg for acute: APR ) Oxaliplatin, or anthracycline, or cyclophosphamide Moderate (other) Low and Minimal DELAYED Nausea and Vomiting: SUMMARY DEX = DEXAMETHASONE DEX can be considered No routine prophylaxis No routine prophylaxis MCP = METOCLOPRAMIDE APR = APREPITANT 9

10 Risk for FN: Febrile neutropenia FOLFIRINOX: Intermediate (10-20%) (NCCN); gr 3/4 Neu: 46% Gemcitabine: Low (< 10%) Gemcitabine + Nab-Paclitaxel: Low (< 10%) Supportive Care Goal: Oncologic emergency Prevention and treatment of FN ESMO FN guidelines 2016 NCCN myeloid GFs guidelines 2017 Conroy T, et al. N Engl J Med 2011; 364: Hosein PJ, et al. BMC Cancer 2012; 12:199 Von Hoff DD, et al. N Engl J Med. 2013;369:

11 Patient risk factors for FN Age 65 yrs Advanced disease History of prior FN Poor performance / nutritional status Mucositis Liver disfunction (elevated bilirubin), renal disfunction (creatinine clearance < 50) ESMO FN Guidelines, 2016 ASCO WBC GFs Guidelines, 2015 NCCN Myeloid GFs Guidelines, 2017

12 FN: Primary prophylaxis 20% Prophylactic G-CSF Chemotherapy related FN risk 10%-20% Patient & Disease related risk Overall FN risk ESMO 2016 ASCO 2015 NCCN 2017 guidelines Risk of FN 20% Risk of FN 20% Alternative regimens 10% NO Prophylac tic G-CSF

13 Neutropenic patient Altered ability to mount a normal immune response Signs & symptoms of infection may be minimal Fever: the principal, the earliest and commonly the only sign of infection Afebrile neutropenic patient who is receiving corticosteroids, NSAIDs Unless recognized & treated, infection can quickly progress to sepsis and death

14 Febrile + neutropenic Afebrile + neutropenic + SIRS or clinical focus of infection Modification of empirical regimen : Clinical and / or microbiological demonstration of infection Blood cultures & Empirical therapy ESMO FN 2016 guidelines

15 RISK PREDICTION FOR FN: MASCC SCORE Burden of illness No/ mild symptoms 5 Moderate symptoms 3 NO hypotension (systolic BP > 90mm Hg) 5 NO COPD 4 Solid tumor or lymphoma with no previous fungal infection 4 No dehydration 3 Outpatient status (at the onset of fever) 3 Age < 60 yrs 2 MASCC score 21: low risk of complications MASCC score < 15: a high mortalty rate

16 High risk Hospitalisation IV antibiotics: PIP-TZ Cefepim Ceftaz IMP MER ± Aminoglycoside Febrile neutropenia MASCC score Low risk: MASCC 21 CIP or Levo PO + AM-CL or Clinda PO Outpatient management? ESMO FN 2016; ASCO outpatient FN 2013

17 Diarrhoea Assessment: NCI-CTCAE & PROs FOLFIRINOX: 12.7% (gr 3 & 4) Gemcitabine: 1-1.8% (gr 3 & 4) Gemcitabine + Nab-Paclitaxel: 6% (gr 3& 4) 5FU: bolus IV vs. infusion regimen Irinotecan: acute and late diarrhoea Mechanism: mucositis, panenteritis, enterocolitis Conroy T, et al. N Engl J Med 2011; 364: Von Hoff DD, et al. N Engl J Med. 2013;369: Andreyev J., et al. Lancet Oncol 2014; 15: e447-60

18 Diarrhea: Consequences Volume depletion Renal insufficiency Electrolyte disorders Intestinal hemorrhage / perforation Infection / sepsis (neutropenia!) Abdominal cramps Malnutrition Decrease in QoL, comfort, dignity Reduced compliance with treatment

19 Fever Complicated diarrhea Abdominal cramping Anorexia, nausea, vomiting Increased weakness Decreased urine output Gastrointestinal bleeding Deteriorated PS Andreyev J., et al. Lancet Oncol 2014; 15: e447-60

20 Diarrhea: treatment Complicated: NCI CTCAE gr 3&4 or 1&2 w/ warning signs Pharmacological Loperamide: first-line Tx for CID Octreotide: first & second-line Tx for CID Steroids (oral, IV): immunotherapy Antibiotics Non-pharmacological Fluid and electrolyte replacement Dietary modifications ASCO 2004; MASCC / ISOO 2104 Andreyev et al., Lancet Oncol 2104; 15:

21 Oral mucositis: Consequences PAIN BLEEDING Thrombocytopenia Mucosal damage Neutropenia INFECTION INABILITY TO EAT/DRINK

22 1 Oral mucositis: pain 2 3 Topical anesthetics / analgesics Topical coating agents Basic oral care protocols 4 Systemic analgesia

23 Oral mucostis pain Benzydamine mouthwash: the prevention of OM in H&N (RT: up to 50 Gy) w/o concomitant CHT Systemic Zn supplements PO: the prevention of OM (RT, C-RT) Coating agents: Not sufficient evidence MASCC suggestion in favor of: o TD fentanyl o Morphine 2% mouthwash o Duloxetine 0.5% mouthwash Peterson DE, et al. Oral & GI mucositis. ESMO clinical practice guidelines 2016

24 CIPN: Diagnosis Neurotoxic CHT (oxaliplatin, nab-paclitaxel) Symptoms: sensory > motor > autonomic ± pain Distribution: distal, symmetric stocking & glove Excluded neuropathy due to cancer (direct: infiltration/compression; indirect effect) Validated patient-reported tools (EORTC-QLQ-CIPN20) No need for formal neurologic testing EORTC-QLQ-CIPN20 ; FACT/GOG-Ntx,; NCI CTCAE ; TNS, total neuropathy score

25 CIPN: Oxaliplatin Acute neurotoxicity (sensory & motor Sx) Chronic, cumulative, dose-dependent CIPN: similar to cisplatin (sensory) (IDEA, ASCO 2017) Prevention Acute neurotoxicity: avoid exposure to cold CIPN: ASCO recommended against the use of IV Ca/ Mg supplementation / any other agent CIPN: stop & go preventive approach Treatment: pharmacological (ASCO 2014 guidelines)

26 CIPN: Prevention & Treatment No established prevention of CIPN For the treatment of CIPN, clinician may offer duloxetine Inconclusive data, but therapeutic trials reasonable nortriptyline, desipramine pregabalin, gabapentin compounded topical gel (baclofen, amitriptyline HCL, ketamine) ASCO guidelines Hershman DL, et al. J Clin Oncol. 2014;32:

27 Supportive Care Makes Excellent Cancer Care Possible

28 Hotel Falkensteiner Belgrade, December 01/02, 2017 The Second Regional Education Meeting On Supportive Care in Cancer Patients for Eastern European and Balkan region