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Systemic management of pancreatic cancer:
Supportive care
Snežana Bošnjak
Institute for Oncology and Radiology of SerbiaDept. Supportive Oncology & Palliative Care
Serbia, Belgrade
Integrative Oncology
Patient-centered model of care: Integrates disease-directed interventions
with patient-family directed interventions (supportive & palliative care)
Involves patients in the decision-making process (PROs)
Improves patient’s QoL and overall clinical outcomes (including survival)
Jordan K, Aapro M, Kaasa S, et al. Annal Oncol 2018; 29: 36–43Basch E, Deal AM, Dueck AC et al. JAMA 2017; 318(2): 197–198.
Hui D, Bruera E. Nat Rev Clin Oncol 2016; 13: 159–17
ESMO position statement on supportive and palliative careJordan K, et al., Annals of Oncology 29: 36–43, 2018
Patient-centered Care (ESMO)
„The oncologist role is not only to deliver the best quality anticancer treatment but also to consider the
impact of the disease and treatment on each patient’s life“
ESMO position paper on supportive and palliative care, Jordan K, et al. Annals of Oncology 2018; 29: 36–43
Metastatic Pancreatic Cancer : Patient Centered Care (ASCO, 2018)
• Assessment: Symptom burden, psychological status,
and social supports as early as possible, preferably at the first visit
• Treatment: Aggressive Tx of the pain and Sx of the
cancer and / or the cancer-directed therapy • A formal PC consult and services
Metastatic Pancreatic Cancer: ASCO Guideline.Sohal DPS et al. J Clin Oncol 2016 34:2784-2796
Guideline Update. Sohal DPS et al. DOI: 10.1200/JCO.2018.78.9636 Journal of Clinical Oncology - published online before print May 23, 2018
Palliative careSupportive care
Hospice care
Conceptual framework for supportive care, palliative care and hospice care, based on the systematic literature review.
No evidence of disease
Curable cancer Incurable cancer Bereavement
Death
Conceptual Framework for Supportive and Palliative Care
Hui D, Bruera E. Nat Rev Clin Oncol 2016; 13: 159–171.
Metastatic Pancreatic Cancer : Supportive Care Guidelines
• Antiemetics (ESMO, 2016)
• Oral and GI mucosal injury (ESMO, 2015)
• Febrile neutropenia (ESMO, 2016)
• Chemotherapy induced peripheral neuropathy (CIPN) (ASCO, 2014)
www.esmo.orgwww.asco.org
FOLFIRINOX vs Gemcitabine: AEs
Grade 3/4 AE, % FOLFIRINOX (n = 171)
Gemcitabine (n = 171)
P Value
Hematologic Neutropenia 45.7 21.0 < .001 Febrile neutropenia: 43% w/GCSF 5.4% 1.2 .03 Thrombocytopenia 9.1 3.6 .04
Nonhematologic Fatigue 23.6 17.8 NS Vomiting 14.5 8.3 NS Diarrhea 12.7 1.8 < .001 Sensory neuropathy 9.0 0 < .001 Elevated ALT 7.3 20.8 < .001
* Conroy T, et al. N Engl J Med. 2011;364:1817-1825.Slide credit: clinicaloptions.com
MPACT: Gemcitabine ± NAB-Paclitaxel—AEs
Event Gem + NAB-Pacli(n = 421)
Gem (n = 402)
AE leading to death 4 4Hematolgic 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;369:1691-1703. Slide credit: clinicaloptions.com
Chemotherapy induced nausea and vomiting (CINV)
The risk for CINV: • FOLFIRINOX: moderate, determined by oxaliplatin /
irinotecan • Gemcitabine: low • Gem+ Nab-Paclitaxel: low
Supportive Care Goal: Prevention and control of CINV (0-120h) Gr ¾ vomiting: 15% after FOLFIRINOX
Overall risk for nausea & vomiting after chemotherapy
• Emetogenicity of chemotherapy • Patient-related risk factors for CINV*
• Disease-associated symptoms & concomitant medications
Nausea and vomiting due to advanced cancer, the use of opioids for pain
Roila F et al. MASCC / ESMO consesus guidelines Ann Oncol (2016) 27 (suppl 5): v119-v133
Dranitsaris G, et al. Annals Oncol 2017; 28: 1260-1267
Increased riskFemale genderYounger age
Morning sicknessAnxiety
Decreased risk
Chemotherapy-naïveAlcohol abuse
CINV prevention: MEC groupACUTE DELAYED
Carboplatin 5HT3+DEX+NK1 -5HT3+DEX+APR APR
Oxaliplatin 5HT3+DEX DEX*
Irinotecan 5HT3+DEX None
Roila et al., Annals of Oncology 2016; 27 (Supplement 5): v119–v133Hesketh PJ, et al. J Clin Oncol 2017; 35(28):3240. Epub 2017 Jul 31.
Hesketh Pj, Bosnjak S, Nikolic V, Rapoport B. Support Care Cancer 2011; 19: 2063-66
Febrile neutropenia FOLFIRINOX: Intermediate risk (10-20%); Gemcitabine + Nab-Paclitaxel: Low (< 10%) Gemcitabine: Low (< 10%)
ESMO FN guidelines 2016NCCN myeloid GFs guidelines 20178
Conroy T, et al. N Engl J Med 2011; 364:1817-25Hosein PJ, et al. BMC Cancer 2012; 12:199
Von Hoff DD, et al. N Engl J Med. 2013;369:1691-1703
Oncologic emergencySupportive Care goal: prevention & empirical treatment
FOLFIRINOX: FN: 5% (43.% with GCSF)NAB-Paclitaxel: FN:3% (26% with GCSF)
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 ml/min)
ESMO FN Guidelines, 2016ASCO WBC GFs Guidelines, 2015
NCCN Myeloid GFs Guidelines, 2017
Chemotherapy related FN risk
≥ 20%
Prophylactic G-CSF
<10%
NO Prophylac
tic G-CSF
10%-20%
Patient & Disease related risk
Risk of FN ≥ 20% Risk of FN <20%
• ESMO 2016 • ASCO 2015• NCCN 2017 guidelines
FN: Primary prophylaxis Alternative regimens
Overall FN risk
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
Febrile + neutropenicBlood
cultures & Empiricaltherapy
Modification of empirical regimen :
Clinical and / or microbiological demonstration of infection
Afebrile + neutropenic + SIRS or clinical focus of infection
ESMO FN 2016 guidelines www.esmo.org
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 2MASCC score ≥ 21: low risk of complicationsMASCC score < 15: a high mortalty rate
www.mascc.org
Febrile neutropenia
Clinical criteria (ASCO, 2018)Risk assessment tools (ie. MASCC score)
High risk Low risk:
HospitalisationIV antibiotics:
PIP-TZCefepimCeftazIMPMER
± Aminoglycoside
CIP or Levo PO+AM-CL or Clinda PO
Outpatient management ?
ESMO FN 2016; ASCO outpatient management of FN 2018
Diarrhoea
• Assessment: NCI-CTCAE & PROs FOLFIRINOX: 13% (gr 3 & 4) Gemcitabine + Nab-Paclitaxel: 6% (gr 3& 4) Gemcitabine: 1-1.8% (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; 364:1817-25Von Hoff DD, et al. N Engl J Med. 2013;369:1691-1703
Andreyev J., et al. Lancet Oncol 2014; 15: e447-60
Diarrhea: Consequences
• Volume depletion • Renal insufficiency• Electrolyte disorders • Intestinal hemorrhage / perforation • Infection / sepsis (neutropenia!)• Abdominal cramps • Malnutrition• Decrease in QoL, dignity• Reduced compliance with treatment
Complicated diarrhea: warning signs
• Fever (is the patient neutropenic?)• Abdominal cramping • Anorexia, nausea, vomiting• Increased weakness• Decreased urine output • Gastrointestinal bleeding • Deteriorated PS
Andreyev J., et al. Lancet Oncol 2014; 15: e447-60
Diarrhea: treatment• Is it complicated (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 2104Andreyev et al., Lancet Oncol 2104; 15: 447-60
Chemotherapy-induced peripheral neuropathy (CIPN)
The risk for CIPN: • FOLFIRINOX: 9%• Gem+ Nab-Paclitaxel: 17%
Supportive Care Goal: Screen for CIPN and diagnose it early
Conroy T, et al. N Engl J Med 2011; 364:1817-25Von Hoff DD, et al. N Engl J Med. 2013;369:1691-1703
CIPN: Oxaliplatin• Acute neurotoxicity (sensory & motor Sx)• Chronic, cumulative, dose-dependent: mainly
sensory, similar to cisplatin• Prevention Acute neurotoxicity: avoid exposure to cold No established agents recommended for the
prevention of chronic CIPN except decreasing the dose or duration of oxaliplatin
ASCO recommends against the use of IV Ca/ Mg supplementation / any other agent
„Stop & go“ preventive approach
ASCO guidelines Hershman DL, et al. J Clin Oncol. 2014;32:1941-67.
IDEA: Safety
Slide credit: clinicaloptions.com
Grothey, A.F. Sobrero, A.F. Shields, et al., N Engl J Med 2018; 378:1177-88
AE, %FOLFOX CAPOX
3 Mos 6 Mos P Value* 3 Mos 6 Mos P Value*Any event† Grade 2 Grade 3/4
3238
3257
< .0001 4124
4837
< .0001
Neurotoxicity Grade 2 Grade ¾
143
3216
< .0001 123
369
< .0001
Diarrhea Grade 2 Grade 3/4
115
137
< .0001 107
139
.0117
*For Chi-squared test for trend.†19 grade 5 events reported.
Safety: main nonhematologic AEs
Presented By Thierry Conroy at 2018 ASCO Annual Meeting
CIPN: Treatment • For the treatment of established painful 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;32:1941-67.
Learning to Care