Oncology

ANTIEMETICS

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1) Acute onset: 0–24 hours after chemotherapy
2) Delayed onset: > 24 hours after chemotherapy

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3) Anticipatory vomiting : triggered by sights, smells, or sounds and is a conditioned response with poor control N,V in
previous chemotherapy
4) Breakthrough emesis: occurs despite prophylactic treatment & required rescue medication.

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5) Refractory emesis: occurs during treatment cycles when antiemetic prophylaxis has failed in previous cycles.

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Emetogenicity of IV chemotherapy agents ra
High Emetic Risk Moderate Risk Low Risk Minimal Risk
Cisplatin Carboplatin Paclitaxel Vinca alkaloids
Cyclophosphamide>1500 Irinotecan-Oxaliplatin Bleomycin
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Ifosfamide> 2 gm
Doxorubicin > 60 Doxorubicin < 60 Liposomal Doxorubicin
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Epirubicin > 90 Epirubicin<90

Cytrabine > 200 Cytrabine(100-200) Cytrabine <100
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MTX >250 MTX(50-250) MTX<50

Amifostine > 300 Amifostine < 300
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Emetogenicity of ORAL chemotherapy agents

High to moderate Risk Low to Moderate Risk
(Prophylaxis as needed)
Cyclophosphamide>100 Cyclophosphamide <100
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Busulfan>4 Busulfan<4
Etopsoide MTX
Mitotane Sorafenib
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Radiation Therapy
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Mild Emetogenic Moderately Emetogenic Highly Emetogenic

Head, Neck & extremities Upper abdomen or pelvis or Total body irradiation
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craniospinal radiation Total nodal irradiation

Upper half-body irradiation

Antiemetics
Serotonin-receptor Adverse Effects: LFTs, QT prolongation, Headache & Constipation
Equally efficacious at equivalent dosages; therefore, the antiemetic DOC is often based on cost and
antagonists organizational contract.
(dolasetron, Dolasetron: Oral form ONLY is now indicated in CINV.
granisetron, Palonosetron is given as IV push 30 minutes before chemotherapy administration & is indicated in:
 Acute CINV for highly emetogenic chemotherapy
ondansetron, &  Acute and delayed CINV for moderately emetogenic chemotherapy.
palonosetron)  May be used before the start of a 3-day chemotherapy regimen instead of several daily doses of oral or
 IV serotonin-3 receptor antagonists
Dexamethasone: has been studied more often in clinical trials.
Corticosteroids Methylprednisolone
Rapid Infusion → Vaginal or anal burning.
In combination → preventing acute and delayed nausea and vomiting with initial and repeat courses of
chemotherapy
Dose: 125 mg on day 1, then 80 mg on day 2 and 80 mg on day 3
NK1 receptor
Fosaprepitant dose: 150 mg IV on day 1 only
antagonists
(aprepitant or Prevention of delayed nausea and vomiting with initial and repeat courses of emetogenic drugs
Dose : 180 mg orally on day 1 only in combination with dexamethasone on days 2 and 3
fosaprepitant)
Drug Interaction:
↓ Oral Contraceptive effect → Change Birth Control Method
↓ Warfarin so check INR within 7–10 days.
↑ Dexamethasone →↓Dexamethasone by 40% in Oral dose only in 2 or 3 day
Netupitant/ preventing acute and delayed nausea and vomiting with initial and repeat courses of chemotherapy

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palonosetron for acute phase, and netupitant for both acute and delayed phases.
palonosetron

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Dosage: 1 capsule once on day 1
Update 2016 Caution in patients with hepatic dysfunction or ESKD
i. Anterograde amnesia helps prevent anticipatory nausea and vomiting & Relief of anxiety

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lorazepam ii. Management of akathisia caused by phenothiazines, butyrophenones, or metoclopramide

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Alternative agent for the prevention of nausea/vomiting in highly emetogenic & for breakthrough CINV.
Gives higher rate of nausea control than aprepitant in highly emetogenic chemotherapy regimens in the
delay onset nausea
Olanzapine

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Olanzapine has been associated with an increased risk of hyperlipidemia, hyperglycemia, and new onset diabetes.
Caution in elderly patients due to increased risk of death and CVD in patients with dementia-related psychosis

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(BLACK BOX WARNING)
Metoclopramide: For prevention & ttt of delayed symptoms
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Prochlorperazine, Chlorpromazine (preferred in children) & Promethazine: For highly Emetogenic regimens
Haloperidol & Droperidol but Droperidol is not recommended due to ↑risk of QT prolongation or Tdp
Cannabinoids (dronabinol, nabilone) Appetite stimulation used when other regimens fail to stimulate appetite.
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Clinical Pearls:
1. [Metoclopramide + Dexamethasone] was the most common regimen to prevent delayed nausea and vomiting before the availability of
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aprepitant. This combination is still used when aprepitant has not been incorporated into the initial regimen for CINV.
2. Single-agent phenothiazine, butyrophenone, or steroids are used for mildly to moderately emetogenic regimens and breakthrough
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symptoms.
3. Consider using a H2-Blockers or PPI to prevent dyspepsia.
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Emetogenicity
Emesis Treatment Day 1 Emesis Treatment Day 2-3&4
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Level
Neurokinin-1 antagonist (Aprepitant , Fosaprepitant or - If aprepitant PO given day 1, aprepitant
Rolapitent) 80 mg PO daily on days 2 and 3
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AND - If fosaprepitant given on day 1, no

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Serotonin 5-HT3 antagonist further aprepitant needed on days 2 and

AND 3.
Steroid Dexamethasone dosage is twice daily on
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days 3 and 4.
High OR Netupitant /palonosetron Once
AND Dexamethasone OR Dexamethasone daily on days 2 and 3

OR Olanzapine-containing regimen: OR Olanzapine-containing regimen:

1. Olanzapine PO day 1 Olanzapine days 2–4 (if given day 1)
2. Palonosetron IV day 1
3. Dexamethasone IV day 1
Neurokinin-1 antagonistis optional in the regimen here Serotonin 5-HT3 antagonist

Moderate OR OR Steroid monotherapy daily on days 2

Netupitant/palonosetron AND Dexamethasone and 3
OR OR Neurokinin-1 antagonist
 Olanzapine-containing regimen:
1. Olanzapine PO day 1 OR Dexamethasone daily on days 2 and 3
2. Palonosetron IV day 1
3. Dexamethasone IV day 1± Lorazepam OR Olanzapine days 2–4 (if given day 1)

Steroid OR Metoclopramide PRN OR Prochlorperazine PRN The same as Day 1

LOW OR Serotonin-3 antagonists (oral therapy) daily

Pain Management
For severe persistent pain use LA regular not PRN pain killer and combine the long acting with rapid-acting product.
Pain Rating Scales:

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a) Numeric rating scale of 0–10, with 0 = no pain and 10 = worst pain imaginable
b) Pediatric patients: Faces-of-Pain Scale, poker-chip method  But Now ,Because pain is subjective, it best evaluated by pt

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Mild- moderate pain (1-3) Moderate- severe pain (4-6) Severe pain (7-10)
“Non-opioid analgesic drug (NSAID), Add a weak opioid: Codeine or hydrocodone, Replace the weak opioid with a

aspirin, or acetaminophen (APAP)
OR Consider slow titration of SA
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available in combination with non-opioid strong opioid: Morphine, oxycodone,
analgesic drugs. (may consider SA opioids) or similar drug.

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opioids either PRN or as scheduled
In opioid-naive patients experiencing severe pain:

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SA opioids should be rapidly titrated then start maintenance on the LA or extended releases.
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NSAIDs There is a ceiling effect to the analgesia provided by NSAIDs Always used as add on
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Combinations Aspirin or APAP or ibuprofen + codeine or hydrocodone or oxycodone
Dose escalation of one component necessitates escalation of the other(s).
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Morphine least-expensive Oxycodone: Available as a single drug (SA & LA)

Alternative to morphine
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Fentanyl Hydromorphone (IV & Oral)

Transmucosal and buccal fentanyl are used for Alternative to morphine with higher potency,
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breakthrough pain. especially in patients with renal dysfunction

Each transdermal patch provides sustained release
of drug and can provide pain relief for 48–72 hours.
Methadone
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Opioid I. In maintenance treatment for opioid-dependent individuals as well as an effective analgesic in

analgesic patients taking opioids long term for moderate to severe pain
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II. Associated with QT prolongation and/or TdP

III. Effective LA agent also used for neuropathic pain , should Start low and titrate slowly.
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Adverse Events: Tolerance develops for all S.E except Constipation

1. Sedation:
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If not tolerated ↓opioid dose if possible if not possible add CNS stimulant ( dextroamphetamine or
methylphenidate ) to reduce the sedation state
2. Constipation  Regular use of stimulant laxative.
3. Urinary retention and bladder spasm common in older adults and with LA agents
 ↓pain and no. of SKE in patients with breast cancer and multiple myeloma if given for 1 yr
 Metastatic Breast cancer patients should receive pamidronate 90 mg delivered over 2 hours or zoledronic
Bisphosphona acid 4 mg over 15 minutes every 3–4 weeks.
tes  Initiate oral calcium plus vitamin D to prevent hypocalcemia.
 Ostenonecrosis of the Jaw: Patient education and education of dentists are important. Patients should
have a dental examination with preventive dentistry before treatment with bisphosphonates.
For Prevention of skeletal-related events (SRE) in patients with bone metastases from solid tumors
Denosumab AE.: UTI or RTI, cataracts, constipation, rashes, and joint pain
Contraindications: Hypocalcemia. Patients should be taking calcium/vitamin D.
 No adjustment for hepatic or renal dysfunction is needed. "EXAM"
1. Antidepressants (e.g., amitriptyline, duloxetine) and anticonvulsants (e.g., gabapentin, carbamazepine,
pregabalin) are used for neuropathic pain
2. Transdermal lidocaine is useful in localized neuropathic pain.
3. Corticosteroids are useful in pain caused by nerve compression or inflammation, lymphedema, bone pain,
Adjuvant
or ↑ICP
analgesics 4. Diazepam, lorazepam: For muscle spasms; baclofen is another alternative for intractable muscle spasms
5. Strontium-89: Radionuclide for treatment of bone pain caused by osteoblastic lesions; a single dose may
provide relief for several weeks or even months; however, it is myelosuppressive
6. NSAIDs are recommended for the treatment of pain caused by bone metastases. "EXAAM"

THROMBOCYTOPENIA

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Definition: platelet < 100,000/mm3; however, the highest risk of bleeding occurs with platelet count ≤20,000

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Oprelvekin (interleukin-11): Not currently used in clinical practice.
A daily SC inj. approved for the prevention of severe thrombocytopenia in patients undergoing chemotherapy for non-myeloid
malignancies. It begins 6–24 hours after completion of myelosuppressive chemotherapy, continued until a post-nadir plt ≥50,000 ;

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dosing beyond 21 days is not recommended, and oprelvekin must be discontinued at least 2 days before (the next cycle of)

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chemotherapy.
SE.: edema, shortness of breath, tachycardia, and conjunctival redness

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Anemia and Fatigue (HB<13 in men, HB<12 in Women)
Microcytic Anemia Macrocytic Anemia = Megaloblastic

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↓RBC, HB/HCT, MCV, MCHC, Iron, ferritin, TIBC Vitamin B12 and folate deficiency
and ↑RBC distribution width (RDW) B12 Folate
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↓RBC, HB and HCT, and serum B12, ↓RBC, HB and HCT, ↑MCV, ↑MCH
Treatment: ↑MCV, MCH, and ↑Homocysteine. B12 will be normal but folate is
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Oral iron taken with food to ↓GIT S.E for 3–6 deficient
months Treatment: Oral replacement daily or
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Vitamin C  ↑Absorption of iron IM replacement weekly for 1 month, Treatment: 1 mg of folate daily
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then monthly. for 4 mth

Anemia in Cancer Patients
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A. Epoetin and darbepoetin alfa: Approved for treating chemotherapy-induced anemia, to ↓need for transfusion. "REMS"
In order to give ESA, the following 3 conditions should be fulfilled:
1- HB < 10 g/dL.
2- Chemotherapy-associated anemia NOT cancer-associated anemia.
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3- Non-curative setting ONLY

SE.: HTN, Seizures, VTE, and pure red cell aplasia (rare)
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EXAAAM:
Evaluate after 4 wks (6 wks if Darbapoetin) and increase dosage if rise is <1 g/dL
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Decrease by ~25% (40 if Darbapoetin) if rapid rise in hemoglobin

Discontinue therapy if no response after 8 weeks
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B. Transfusions are an option if patients are symptomatic. Transfusion goal is to maintain hemoglobin between 8 and 10
CHEMOPROTECTANTS
Dexrazoxane
-The anthracyclines (daunorubicin, doxorubicin, idarubicin, and epirubicin), anthracenedione, and mitoxantrone can cause
cardiomyopathy that is related to the total lifetime cumulative dosage. EXAAAM
-Dexrazoxane is approved for use in patients with metastatic breast cancer. It may be considered for patients who have received
doxorubicin ≥ 300 mg/m2 and who may benefit from continued doxorubicin, considering the patient’s risk of cardiotoxicity with
continued doxorubicin use.
-Dexrazoxane is also approved for use as an antidote for the extravasation of anthracycline chemotherapy.
Amifostine
Amifostine is used to prevent nephrotoxicity from cisplatin.
↓Acute and late xerostomia in patients with head and neck Cancer undergoing fractionated radiation therapy
S.E: N.V & HYPOTENSION  with the concomitant antihypertensive medications, using hydration, and close monitoring of BP.
Mesna (sodium-2-mercaptoethane sulfonate)
The metabolite acrolein is produced from cyclophosphamide (≥1500 mg/m2) & ifosfamide  Sterile hemorrhagic cystitis.
1. Mesna detoxifies acrolein (given orally or IV )
2.Mesna must begin concurrently with or before ifosfamide or cyclophosphamide and end after ifosfamide or cyclophosphamide
ONCOLOGIC EMERGENCIES
Hypercalcemia
Metastatic non–small cell lung cancer causes more Hypercalcemia > Small cell lung cancer, breast, multiple myeloma, head and
neck, renal cell, and non-Hodgkin lymphoma.
HT, thiazides may precipitate or exacerbate hypercalcemia.
Management of hypercalcemia:
Mild hypercalcemia (corrected calcium Hydrate with NS followed by observation is an option in asymptomatic patients with

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<12 mg/dL) chemotherapy-sensitive tumors (e.g., lymphoma, breast cancer).

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Moderate hypercalcemia (corrected Requires basic treatment of clinical symptoms with aggressive hydration and it’s not
calcium 12–14 mg/dL) emergency to treat using bisphosphante
Aggressive inpatient treatment:

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i. Hydration with NS

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ii. Loop diuretics may be administered after volume status has been corrected or to
prevent fluid overload during hydration..
Severe hypercalcemia (corrected

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iii. Bisphosphonates and The onset of action is 3–4 days.
calcium>14 mg/dL; symptomatic)
iv. Calcitonin IM: monitor for its hypocalcemic effect.
v. Steroids in patients with steroid-responsive tumors (lymphoma and myeloma).

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vi. If hypophosphatemic + hypercalcemic  Phosphate
vii. If hypercalcemia + renal failure.  Dialysis
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Spinal Cord Compression
Treatment consists of dexamethasone and radiation therapy or surgery.
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Tumor Lysis Syndrome
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Secondary to the rapid cell death that follows the administration of chemotherapy in patients with high tumor burdens. EXAM
Manifestations: ↑Uric, ↑K, ↑P, ↓Ca  Can lead to renal failure.
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The primary management strategy

1. Prevention with IV NS hydration and allopurinol.
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2. Rasburicase: For patients at high risk of developing TLS, such as those with a serum uric > 8 mg/dL, a large tumor burden,
preexisting renal dysfunction, or an inability to take allopurinol. The drug is expensive, and currently it is not recommended for
prophylaxis in all patients but may be used together with hydration for treatment of TLS.
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MISCELLANEOUS ANTINEOPLASTIC PHARMACOTHERAPY

Extravasation Injuries
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Occurs with doxorubicin, daunorubicin, epirubicin, mechlorethamine, mitomycin, vincristine, vinblastine, vinorelbine, and
streptozocin. [Anthracyclines cause the most severe tissue damage on extravasation].
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 It is recommended to administer them by IV injection rather than infusion, but some exceptions exist.
Management:
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1- Cold for doxorubicin, daunorubicin, and epirubicin

2-Heat for vincristine, vinblastine, and vinorelbine
3-Sodium thiosulfate for mechlorethamine
4- Dexrazoxane for doxorubicin, daunorubicin, idarubicin, and epirubicin.
Cold compress should be removed 15 minutes before dexrazoxane treatment.
Management of Diarrhea
1. Intensive high dose loperamide therapy for irinotecan- induced diarrhea.
2. Atropine is used to prevent cholinergic activity of acute irinotecan-induced diarrhea.
Dosage Adjustment for Organ Dysfunction
1. Renal adjustment with MTX, carboplatin, cisplatin, etoposide, bleomycin, topotecan, capecitabine,lenalidomide. (MCCEBTL)
2. Hepatic adjustment is often based on total bilirubin concentrations.