Tatalaksana Anemia pada

Keganasan
dr. Heri Fadjari
Anemia
• Definisi : penurunan level Hb (Hemoglobin) ringan – sedang, yang biasanya
berkaitan dengan inflamasi akut atau kronis dari dalam tubuh. Inflamasi ini
nantinya akan berpengaruh pada cadangan besi tubuh maupun
eritropoiesis.
• Etiologi :
• Bone marrow failure
• Blood loss
• Penghancuran sel darah merah (eritrosit) yang berlebih
• Morfologi :
• Mikrositik
• Makrositik
• Normositik
Definisi Anemia menurut WHO
• Anak – anak
• Usia 6 – 59 bulan  Hb < 11 g/dL
• Usia 5 – 11 tahun  Hb < 11.5 g/dL
• Usia 12 – 14 tahun  Hb < 12 g/dL
• Wanita (usia ≥ 15 tahun)
• Tidak hamil  Hb < 12 g/dL
• Hamil  Hb < 11 g/dL
• Pria (usia ≥ 15 tahun)  Hb < 13 g/dL
Gejala Anemia
Central nervous system Immune system
• Fatigue • Impaired T-cell and
• Dizziness macrophage function
• Depression
• Impaired cognitive function Cardio-respiratory system
• Exertion dyspnoea
Gastrointestinal system • Tachycardia, palpitations
• Anorexia • Hypertrophy
• Nausea • Risk of cardiac failure

Vascular system Genital tract

• Low skin temperature • Menstrual problems
• Pallor of skin • Loss of libido

Ludwig H & Fritz D, 1998

Penyebab Anemia pada Keganasan
• Usia
• Blood loss  misalnya : post surgery
• Penyakit kronis
• Obat konkomitan (misalnya : NSAID, aspirin)
• Gastritis uremikum
• Makanan (terutama pada vegetarian)
• Defisiensi folate / vitamin B12
DEFISIENSI BESI pada KEGANASAN

Ludwig et al. Annals of Oncology. 2013 May 29

Defisiensi Besi pada Keganasan di Asia Pasifik
Country Population Patients with Cancer Cancer and ID
TOTAL 3,541,880,259 17,709,401 7,969,231
Australia 22,620,600 113,103 50,896
Bangladesh 150,593,658 752,968 338,836
China 1,344,130,000 6,720,650 3,024,293
Hong Kong 7,071,600 35,358 15,911
India
Sekitar 43% dari semua
1,241,491,960 pasien
6,207,460 2,793,357
Indonesia 242,325,638 1,211,628 545,233
South Korea kanker mengalami Defisiensi
49,779,000 248,895 112,003
Malaysia 28,859,154 Besi (DB) 144,296 64,933
Ref: Ludwig et al. Annals of Oncology 00: 1–7, 2013
Pakistan 176,745,364 883,727 397,677
Philippines 94,852,030 474,260 213,417
Singapore 5,183,700 25,919 11,663
Sri Lanka 20,869,000 104,345 46,955
Thailand 69,518,555 347,593 156,417
Vietnam 87,840,000 439,200 197,640
Population source: The World Bank (2011)
1. Iron Deficiency; 2. Anaemia
Mekanisme Utama Anemia pada Keganasan

1. Adamson JW, 2008; 2. Birgegard G, 2005; 3. Grotto HZW, 2008; 4. Weiss G, 2005; 5. Auerbach M, 2004;
2. 6. Bastit L, 2008; 7. Pedrazzoli P, 2008; 8. Henry DH, 2007; 9. Hedenus M, 2007
Prevalensi dan Terapi Anemia, Defisiensi besi
dan Peranan Besi IV pada Kanker

Aapro et al. Ann Oncol (2012) 23(8): 1954-1962

Guideline Terapi Besi (Fe)
NCCN Guideline 2013 (Summary)


NCCN Guidelines Version 1.2013

NCCN Guideline 2013 (Summary)

NCCN Guidelines Version 1.2013

NCCN Guideline 2014
 Iron Sucrose (Venofer®): Key Clinical Data
Study Design # Pts Iron Sucrose Dosing Key Results
Kim et al. Open label randomised controlled 200mg iron if Hb 10- ↓transfusion needs
Gynecol Oncol. 2007 study 75 12g/dL at each cycle Later NADIR for Venofer patients
Apr;105(1):199-204 Cervical Cancer with
chemoradiotherapy
Hedenus et al. Open label randomised controlled 100 mg iron weekly from ↑Hb (median time to response – 6 wks)
Leukemia. 2007 study weeks 0 to 6 and then ↓EPO requirements
Apr;21(4):627-32 transfusion-independent patients with 67 100mg every 2 weeks from ↑Iron levels (ferritin and TSAT)
stainable iron in the bone marrow and weeks 8 to 14
lymphoproliferative malignancies not (all pts received EPO)
receiving chemotherapy
Bastit et al. Open label randomised controlled 200 mg iron Q3W ↑Hb / EPO response
J Clin Oncol. 2008 Apr study (all pts received EPO) ↓transfusion needs
1;26(10):1611-8 Non-myeloid malignancy patients with 396 ↑improvement in fatigue levels
Hb <11g/dL ↑faster QoL improvement (than
EPO alone)
Dangsuwan et al. Open label randomised controlled 200 mg iron in a ↓transfusion needs
Gynecol Oncol. 2010 study 44 chemotherapy cycle ↑Hb / EPO response
Mar;116(3):522-5 gynecologic cancer patients with Hb (all pts received EPO)
<10g/dL
Iron Sucrose (Venofer®): Key Clinical Data
Kebutuhan Zat Besi
Dilution
Author N* Iron Injection / Infusion Admin Time
(saline)
Kim et al.
Gynecol Oncol. 2007 75 200mg Infusion 200mL >30min
Apr;105(1):199-204

Hedenus et al.
Leukemia. 2007 67 200mg Injection -- --
Apr;21(4):627-32

Bastit et al.
J Clin Oncol. 2008 Apr 396 100 or 200mg Not Stated Not Stated Not Stated
(physician discretion)
1;26(10):1611-8

Dangsuwan et al.
Gynecol Oncol. 2010 44 200mg Infusion Not stated >30min
Mar;116(3):522-5

* Patients receiving IV iron sucrose (Venofer®)

Besi IV mendukung EPO dan/atau menurunkan dosis EPO

1. Auerbach, JCO 2004;22:1301; 2. Hedenus; Leukemia 2007;21:627; 3. Henry, Oncologist 2007;12:231; 4. Bastit,
JCO 2008;26:1611; 5. Pedrazzoli, JCO 2008;26:1619; 6. Auerbach, Am J Hematol 2010;85:655; 7. Steensma, JCO
2011;29:97.
Penambahan Venofer® pada Terapi ESA 
menurunkan dosis ESA yang dibutuhkan

Hedenus et al. Leukemia. 2007 Apr;21(4):627-32

Pemberian dosis tunggal Venofer® menurunkan kebutuhan
tranfusi darah pada pasien kanker dengan kemoterapi

80
Transfused patients

64.0%

Transfused patients (% )
60 80
40.0% 63.6%
(%)

40 60

20 40
22.7%
0 20
No anaemia Iron Sucrose
therapy 0
oral iron iron sucrose

1. Kim YT et al. Gynecol Oncol 2007;105:199

2. Dangsuwan P & Manchana T. Gynecol Oncol 2010;116:522.
Guideline Terapi ESA
Background : The purpose of this study was to evaluate the safety and efficacy of
epoetin alfa (EPO) at an initial dose of 60,000 Units (U) once weekly (QW) followed by
extended dosing of 80,000 U every 3 weeks (Q3W) in patients with chemotherapy-
induced anemia (CIA).
Materials and Methods : Anemic patients (hemoglobin [Hb]≤11 g/dl) receiving Q3W
chemotherapy for nonmyeloid malignancy were enrolled in this prospective, open-label,
single-arm study to receive EPO 60,000 U subcutaneously (SC) QW (initial dosing phase
[IDP]) until a target Hb level of 12 g/dl was reached (maximum 12 weeks). Patients who
achieved an Hb level of 12 g/dl at any point during the IDP then entered the extended
dosing phase (EDP; EPO 80,000 U SC Q3W). Maximum study duration (IDP+EDP) was 24
weeks. The primary endpoint was the proportion of patients achieving a hematopoietic
response (Hb increase≥ 2 g/dl from baseline or Hb≥12 g/dl) during the IDP.
Results : One hundred fifteen patients were enrolled. During the IDP,
76% (84/110) of patients achieved a hematopoietic response, and 15%
(17/115) received red blood cell (RBC) transfusion. Sixty-three percent
(73/115) of patients entered the EDP, and 88% (64/73) of these
patients maintained a mean Hb level>11.0 and ≤13.0 g/dl. Two of 73
patients received RBC transfusion during the EDP. Adverse events were
consistent with the underlying disease and chemotherapy treatment.
Conclusion : These results suggest that initiation
of EPO 60,000 U SC QW is effective in the
treatment of CIA and that EPO 80,000 U SC Q3W
can be an effective extended dosing option.
Take Home Message
• Cancer negatively impacts iron homeostasis and restricts iron uptake
• Iron deficiency is frequently observed in patients with cancer
• Iron deficiency leads to anaemia as well as multiple other complications, not
least of which is fatigue with impact of patient QoL
• IV iron improves ESA responsiveness and decreases required EPO dose
• IV iron (alone or in combination with ESA) can reduce blood transfusion
requirements
• Guidelines recommend assessing iron parameters (serrum ferritin and/or
Aapro et al. Ann Oncol (2012) 23(8): 1954-1962
TSAT) and treating iron deficiency prior to ESA or other anaemia management
strategies
~1 – 2 out of every 3 patients
have iron deficiency
and ~1 in 3 with
anaemia