Transcript dr.manal mostafa cth organ dysfunction

By : Manal Mostafa Saleh
Demonstrator of clinical oncology ,
Nuclear medicine
References :
 Physicians Cancer Chemotherapy Drug Manual
(2015).
 2013-ESMO-Handbook-of-Cancer-Treatments-in-
Special-Clinical-Situations.
 Oncology - An Evidence-Based Approach
(Springer, 2005).
 Successful
administration
of
chemotherapy relies on several critical
patient factors: age; performance status;
co-morbid illnesses; prior therapy; and
baseline hematologic, hepatic, and renal
status.
The
dose
chemotherapeutic
of
agent
a
should
given
be
adjusted accordingly to these parameters.
It is important to treat the patient not to
treat the disease
Renal insufficiency
 GFR (glomerular filtration rate) is the optimal
way to measure kidney function. Generally,
the creatinine clearance is a good estimation
of the glomerular filtration rate.
 There are two main ways doctors use creatinine
tests to measure kidney function:
 24 hours urine collection test. Although the urine
creatinine measurement method is inconvenient,
it may be necessary to diagnose some kidney
conditions.
 GFR can be estimated using a single blood level of
creatinine, which enters into a formula. Different
formulas are available, which take into account
age,sex, and sometimes weight .
 For practical reasons, the blood test estimation
method for GFR is used far more often than the 24hour urine collection test for creatinine clearance.
Different
equations
for GFR
calculation
Normally it is 90 ml/min /1.73m2 or
higher
 Renal insufficiency is defined as a
glomerular filtration rate (GFR) of
consistently less than 60 ml/min/1.73
m2. It is considered chronic when the
condition persists for more than three
months
 impaired renal function is a common condition
in adults and in the elderly, and is a predictor of
diminished survival. Its incidence is high in
cancer patients who are treated regularly with
nephrotoxic molecules. Thus, the clinician’s
dilemma is how to prevent the deterioration of
renal function and determine the adjusted
dosage of a drug with regard to the patient’s GFR
without reducing the effectiveness of potentially
nephrotoxic therapies.
 Changes
should
apply
to
the
disease
management strategy as a whole, from specific
treatment (chemotherapy) to supportive care
(pain relief) and complementaryexaminations
(iodinated contrast).
 In everyday practice, the majority of cancer
therapies require no dose modification for a
creatinine clearance of between 60 and 90
ml/min.
Case 1
 Postmenopausal female patient 55 ys old
acase of breast cancer , now attend for 1st
cycle paclitaxel as adjuvant ttt after 4 FAC ,
CBC and LFT are ok but S.creat
1.6
(calculated cr.clearance 42 ml/min acc. To
CKD equation) , What will you do?
 Give the cycle now
 Good hydration and postpone I cycle 1
week
 Give the cycle with reduction of the dose
For docetaxel
and
paclitaxel No dose
reduction
is
necessary
in
patients with renal
dysfunction.
Chemotherapy metabolized
or excreted through
Kidney
 B Bleomycin
 C (Capecitabine- Carboplatin -Cisplatin-
Cytarabine-cyclophosphamide)
 D Dacarbazine
 E Etoposide
Moti
(methotrexate,mitomycin , oxaliplatin ,temodal,
topotecan , ifosphamide)
 Iodinated contrast-induced acute kidney injury (ICI-
AKI) is the third leading cause of acute kidney failure
during hospitalisation, after antibiotics and NSAIDs.
The main risk factor for ICI-AKI is pre-existing renal
insufficiency.
 The other risk factors are age >65 years, diabetes,
dehydration, concomitant nephrotoxic drug intake,
anaemia and hypoalbuminaemia. Thus, a patient
designated to receive an ICM injection should first be
screened for these risk factors.
Hepatic dysfunction
 Oncologists should be aware of liver toxicity from
anti-cancer drugs, and oversee dosing strategies
for patients with HD. The therapeutic index of
anti-cancer drugs undergoing hepatic metabolism
and biliary elimination is even narrower in the
case of HD, increasing the risk of severe toxicity
and/or impaired activity.
 Often patients present with several causes of HD,
including liver metastases, paraneoplastic
hepatotoxicity,pre-existing liver infections and
concurrent medication .
Case 2
 Male patient 65 ys old acase of metastatic
cancer prostate (bone), failed on hormonal ttt,
the panel descision was starting taxotere
single agent, this is the 1st cycle , CBC is ok ,
S.creat 1.2 , SGPT 45, SGOT 70 What will you
do?
 Give the cycle now
 postpone I cycle 1 week , with liver support
 Give the cycle with reduction of the dose
 Docetaxel is metabolised by liver, followed by
biliary excretion.
 Clearance is 50% of normal in patients with
AST/ALT ≥2.5× ULN and 25% in patients with
TB ≥1.5× ULN..
 Docetaxel should be omitted in patients with
TB >ULN
Docetaxel
 Omit if bilirubin .1.5 mg/dL, SGOT
.60 mg/dL.
Paclitaxel
 No formal recommendation for dose reduction if
bilirubin 1.5–3.0 mg/dL or SGOT 60–180 mg/dL.
 Omit if bilirubin .5.0 mg/dL or SGOT .180 mg/dL.
Paclitaxel
 Normal LF
175 mg/m2/3 w
 AST/ALT >ULN
135 mg/m2/3 w
 Bilirubin 1.25–2× ULN
 Bilirubin 2–3.5× ULN
 Bilirubin >3.5× ULN
115 mg/m2/3 w
100 mg/m2/3 w
Omit
Chemotherapy metabolized 
or excreted through
liver 
C
campto –capcitabine
D
docetaxel , paclitaxel , doxorubicin
 E etoposide
 F flourouracil , vinca alkaloids
 methotrexate
kidney
liver
 B Bleomycin
 C campto –
 C (CapecitabineCarboplatin -Cisplatin
capcitabine
 D docetaxel ,
paclitaxel ,
doxorubicin
 E etoposide
 Flourouracil ,
vinca alkaloids
-Cytarabinecyclophosphamide)
 D Dacarbazine
 E Etoposide
Moti
(methotrexate ,
oxaliplatin ,temodal,
ifosphamide)
 methotrexate
Case 3
 40 ys old hepatic male patient acase of
nasopharyngeal NHL stage I , the panel
decision was chemotherapy CHOP followed by
RTH, ptn received 1st cycle full lab was
satisfactory, attend for 2nd cycle , CBC and
s.creat ok , SGOT 60 , SGPT 45, you asked him
to do T.bilirubin and the result was 1.6
 What will you do??
Cyclophosphamide
 Reduce by 25% if bilirubin 3.0–5.0 mg/dL or
SGOT more than 180 mg/dL.
 Omit if bilirubin .5.0 mg/dL.
Doxorubicin
 Reduce dose by 50% if bilirubin 1.5–3.0 mg/dL.
 Reduce dose by 75% if bilirubin 3.1–5.0 mg/dL.
 Omit if bilirubin .5.0 mg/dL.
Vincristine
 No dose reduction if bilirubin less than 1.5 mg/dL
and SGOT ,60 mg/dL.
 Reduce by 50% if bilirubin 1.5–3.0 mg/dL and
SGOT 60–180 mg/dL.
N.B
 Anastrozole (arimidex) Dose reduction may
be
necessary
in
patients
with
Hepatic
dysfunction but No formal recommendation
for dose reduction.
 Bicalutamide (casodex) Dose reduction may
be necessary if bilirubin more than 3.0 mg/dL
5-Fluorouracil
 No formal recommendations for
dose reduction.
 Omit if bilirubin .5.0 mg/dL.
Chemotherapy in patients with
hepatitis
 Liver injury is a frequent complication of chemotherapy. The
main sources of this injury are drug hepatotoxicity and viral
infections such as hepatitis B virus (HBV), hepatitis C virus
(HCV), cytomegalovirus and herpes simplex virus.
 Liver infections particularly HBV and HCV, have been reported as
causes of severe liver disease, including fulminant hepatitis,
either by reactivation or by enhanced replication of the virus in
the context of induced immunosuppression by chemotherapy
 Risk of HBV reactivation depends on the
balance between replication of the virus and
the host’s immune response. Thus, the risk of
reactivation differs according to the patient´s
HBV infection status prior to chemotherapy as
well as to the degree of immunosuppression
due to systemic chemotherapy.
Risk Factors for HBV Reactivation in HBV-positive
Individuals with Cancer Who Receive Chemotherapy
 HBsAg positivity
 High baseline HBV DNA levels (>105 copies/ml)
 Male gender
 Young age
 High basal serum ALT levels
 Absence or decrease of anti-HBs titres during
chemotherapy
 Type
of
malignancy
(haematological
malignancies: lymphoma)
 Chemotherapeutic
agents:
anthracyclines,
cyclophosphamide, fludarabine, vinca alkaloids
 Steroid-containing regimens
 Monoclonal antibodies: rituximab, alemtuzumab
 Haematopoietic stem cell transplantation (HSCT
Treatment of HCV Reactivation
 At present, treatment of HCV reactivation is
mainly supportive
 Anti-HCV
therapy has traditionally been
avoided during chemotherapy because the
haematological adverse effects of antiviral
drugs
can
exacerbate
chemotherapy.
the
toxicity
of
Prevention of HCV Reactivation
 No drugs are currently approved for the prevention of HCV
reactivation in patients who undergo chemotherapy. The risk of
HCV reactivation may be reduced by using lower doses of
immunosuppressive
drugs
or
giving
less
aggressive
chemotherapy to prevent hepatotoxicity. However, this approach
is not feasible since fatal hepatitis has been described even in
patients treated with only one immunosuppressive agent. Hence,
base line screening for HCV infection is crucial in patients
undergoing chemotherapy, especially in those with lymphoma.
conclusion
 Reactivation of HBV or HCV can occur after
immunosuppression in patients with cancer
who receive chemotherapy. This complication
can be clinically severe and result in
progressive liver disease or death due to liver
dysfunction. Patients needing cytotoxic
agents should be screened forHBV and HCV
infection before initiating chemotherapy.
Periodic monitoring of ALT and HBV or HCV
viral load levels should be performed during
chemotherapy and after treatment is
withdrawn.
 In high-risk patients, HBV reactivation
can be preventable . As current
treatment of HCV may not be used
concomitantly with chemotherapy,
management of HCV reactivation is
mainly supportive