oncology intro

signs of cancer

•Fatigue

•Unexplained weight loss

•Pain that doesn’t go away or gets worse

•Unusual bleeding or bruising

•Fever or nights sweats

•Cough that doesn’t go away (lung cancer)

common chemo toxicities

•GI tract

•Mucositis

•Diarrhea

•Nausea/vomiting

•Bone marrow (monitor complete blood count prior to and throughout therapy)

•Neutropenia

•Anemia

•Thrombocytopenia

•Hair follicles

•Alopecia

Pyrimidine analogues

5-Fluorouracil (5-FU), Capecitabine, cytarabine, gemcitabine

BBW for capecitabine

significant increase in INR/bleed risk with concomitant use of vitamin K antagonists during and up to 1 month after treatment

AE for 5-FU, Cytarabine and Capecitabine:

palmar-plantar erythrodysesthesia (hand-foot syndrome)

high dose cytaribine

associated with CNS and ocular toxicities (administration of ophthalmic corticosteroids given every 4 hours is required while inpatient)

pyrimidine analougue AE

•BOXED WARNING:

•Capecitabine: significant increase in INR/bleed risk with concomitant use of vitamin K antagonists during and up to 1 month after treatment

•5-FU, Cytarabine and Capecitabine palmar-plantar erythrodysesthesia (hand-foot syndrome)

•High-dose cytarabine regimens are associated with CNS and ocular toxicities (administration of ophthalmic corticosteroids given every 4 hours is required while inpatient)

•Diarrhea

•Mucositis

what is given with 5-FU/capecitabine

Leucovorin

•to increase the efficacy of 5-FU, helps 5-FU bind more tightly to target enzyme

when to take capecitabine

•taken with food or within 1 hour after meal to reduce nausea

Dihydropyrimidine dehydrogenase

responsible for the degradation of 5-FU to inactive metabolites. Approximately 5% of the population has a DPD deficiency, a contraindication to the administration of capecitabine/5FU because of an increased risk of potentially life-threatening mucositis, diarrhea, and myelosuppression.

purine analogues

mercaptopurine (6-MP), fludarabine, cladribine

purine ADE

Nausea
Neurotoxicity
Peripheral neuropathy

6-MP DDI

• allopurinol: must reduce 6-MP by 50%. 6-MP depends on xanthine oxidase for an initial oxidation step and allopurinol is a xanthine oxidase inhibitor

• warfarin

folate antagonist

methotrexate and pemtrexed

BBW for methotrexate

•myelosuppression, renal damage, hepatotoxicity, GI toxicity (n/v, stomatitis/mucositis) + more

pemtrexed ADE

severe anemia: patients must take folic acid 400 to 1,000 mcg orally once daily and vitamin B12 1,000 mcg IM every 3 cycles throughout treatment

methotrexate pearls

• RA/Psoriasis methotrexate doses are given weekly, oncology indication given multiple times per week

• High dose methotrexate  (>500mg/m²) requires

  • hydration and IV sodium bicarbonate to alkalinize the urine and decrease risk of nephrotoxicity

  • leucovorin (folinic acid) “rescue” which is the active form of folic acid that does not require activation by dihydrofolate reductase. Folic acid is NOT effective for high dose methotrexate “rescue” 

methotrexate DDI and dose adj

•Methotrexate interacts with NSAIDs and PPIs – these agents decrease clearance of methotrexate

•Methotrexate: adjust dose with renal impairment (avoid pemetrexed in renal impairment)

vinka alkaloids

vincristine, vinorelbine, vinblastine

vinka alkaloid BBW

• Vesicant (cause severe tissue damage, including blistering and necrosis, if they leak out of a vein during administration)

  • Treat extravasation with warm soaks and injection of hyaluronidase

• IV administration only (fatal if given intrathecally)

vinka alkaloid AE

•Neuropathies common because microtubules play important role in transport in neurons

•Peripheral sensory neuropathy (paresthesia)

•Autonomic neuropathy (constipation)

•Vincristine single dose “capped” at 2mg due to neuropathy toxicity

Taxanes

paclitaxel (Taxol), docetaxel (Taxotere), paclitaxel albumin bound (Abraxane)

taxane BBW

•Severe hypersensitivity reactions (due to solvent systems used to maintain solubility, not taxane structure)

•Premedication with steroids, H1RA, and H2RAs required- specific regimens vary by agent

•Abraxane uses different solvent system and does not have this risk or require premedications

taxane ADE

•Neuropathies common because microtubules play important role in transport in neurons

•Alopecia

•Docetaxel: fluid retention (pleural effusion, ascites or edema)- requires premedication with dexamethasone

Topoisomerase I Inhibitors

irinotecan

Topoisomerase I Inhibitors BBW

• Myelosuppression

• Irinotecan: Diarrhea (early and delayed->24 hours)

  • Early (muscarinic): treat with atropine

  • Delayed (secretory): treat with loperamide

Topoisomerase I inhibitor ADE

nausea/vomiting

Topoisomerase I inhibitor pearls

UGT1A1-poor metabolizers have increased systemic exposure to active metabolite and are at increased risk of severe or life-threatening neutropenia with irinotecan

Topoisomerase II Inhibitors

etoposide

Topoisomerase II Inhibitors BBW

myelosuppression

Topoisomerase II Inhibitors ADE

•Hypersensitivity reactions

•Infusion rate-related hypotension 

Anthracyclines

doxorubicin (Adriamycin), doxorubicin liposomal (Doxil), epirubicin

anthracyclines BBW

• Myocardial toxicity

  • Doxorubicin has maximum lifetime dose limit of 450-550mg/m²

  • Get echocardiogram to monitor left ventricular ejection fraction at baseline, specific cumulative doses and after treatment, LVEF should be >50% to administer

• Vesicant (risk is with non-liposomal formulations)

  • dexrazoxane (Totect) -  given if extravasation occurs to prevent tissue necrosis 

• Myelosuppression

anthracyclines ADE

•Alopecia

•Nausea/vomiting

•Drug is red, causes red discoloration of urine and bodily fluids

Nitrogen Mustards

cyclophosphamide, ifosfamide

nitrogen mustards BBW

• Hemorrhagic cystitis

  • Acrolein is a metabolite of ifosfamide and toxic to lining of bladder

  • Ensure adequate hydration and give mesna (Mesnex) to reduce risk

• Myelosuppression

• Neurotoxicity- somnolence, confusion, cerebellar symptoms (usually transient, dose dependent)

nitrogen mustard ADE

•Cyclophosphamide can also cause hemorrhagic cystitis, but not as commonly as ifosfamide

•Highly emetogenic

Platinum Analogues

carboplatin, cisplatin, oxaliplatin

Platinum Analogues BBW

• Anaphylactic-like reaction: risk increases with repeated exposure

• Myelosuppression

• Vomiting (cisplatin is most highly emetogenic chemotherapy)

• Cisplatin:

  • Peripheral neuropathy

  • Nephrotoxicity: dose limit 100mg/m² per cycle due, hydration with 1-3 Liters required prior and post-administration of cisplatin

platinum analogues ADE

• Cisplatin: ototoxicity

• Oxaliplatin: acute sensory neuropathy exacerbated by exposure to cold

• Calvert formula used to dose carboplatin

  • Dose (mg) = target AUC x (CrCl + 25)

  • Use Cockcroft-gault, use actual body weight BMI< 25, use adjusted bodyweight if BMI>25

Nitrosoureas

carmustine (available as IV solution and intracranial implant/wafer), lomustine (oral)

Nitrosoureas BBW

•Pulmonary toxicity (carmustine)

•Myelosuppression

nitrosoureas ADE

•Nausea/vomiting

•Lomustine: oral medication and fatal toxicity occurs with overdosage, should be emphasized that it is only taken once every 6 weeks 

Nitrosoureas pearl

•These agents are highly lipophilic and able to cross the blood brain barrier

Bleomycin MOA

•Bleomycin produces free radicals through intercalation

bleomycin BBW

•Pulmonary fibrosis (maximum lifetime dose limit of 400 units)

•Anaphylaxis

no significant myelosuppression

Monoclonal antibodies premedication

•Cause infusion-related reactions, premedication with diphenhydramine, acetaminophen and/or steroid is usually required.

Vascular endothelial growth factor (VEGF) Inhibitors (monoclonal)

Bevacizumab (Avastin)

Bevacizumab (Avastin) ADE

Impairs wound healing –avoid 1 month before/after surgery, risk of GI perforation, hypertension, proteinuria 

Bevacizumab (Avastin) BBW

severe/fatal bleeding

bevacizumab monitoring

blood pressure and urine protein: creatinine ratio

Human Epidermal Growth Factor Receptor 2 (HER2) Inhibitors (monoclonal)

Trastuzumab (Herceptin) Pertuzumab

Trastuzumab (Herceptin) Pertuzumab pharmacogenomics

test for HER2 gene expression, must have HER2 overexpression to use

Trastuzumab (Herceptin) Pertuzumab BBW

heart failure (monitor LVEF), teratogenic, pulmonary toxicity

HER2 inhibitor conjugated to a microtubule inhibitor (monoclonal)

Ado-trastuzumab emtansine (Kadcyla)

Ado-trastuzumab emtansine (Kadcyla) pharmacogenomics

test for HER2 gene expression, must have HER2 overexpression to use

Ado-trastuzumab emtansine (Kadcyla) BBW

heart failure (monitor LVEF), teratogenic, pulmonary toxicity

Epidermal Growth Factor Receptor (EGFR) Inhibitors (monoclonal)

Cetuximab, Panitumumab

Cetuximab, Panitumumab pharmacogenomics

test for EGFR and KRAS gene expression, must be KRAS wild type to use

cetuximab, panitumumab ADE

acneiform rash (avoid sunlight, wear sunscreen, apply topical steroid and antibiotics prophylactically)

Leukocyte Cluster of Differentiation (CD) Antigens inhibitors (monoclonal)

Rituximab (Rituxan)

CD-20

Rituximab (Rituxan) CD-20 pharmacogenomics

test for B-cell antigen CD20, must be CD20 positive to use

Screen for hepatitis B before therapy initiation

Monoclonal Antibodies- Immune Checkpoint Inhibitors 

pembrolizumab (Keytruda), nivolumab, durvalumab, atezolizumab

pembrolizumab (Keytruda), nivolumab, durvalumab, atezolizumab ADE

•immune related toxicities: colitis, hepatitis, pulmonary toxicity (pneumonitis), nephrotoxicity, thyroid disorders, myocarditis, encephalitis, endocrinopathies (hyperglycemia), fatigue 

•Immune related toxicities may require interruption or permanent discontinuation of treatment, also treated with steroids

Tyrosine Kinase Inhibitors (TKIs) common ADE

•For some TKIs, oral bioavailability may be altered if taken with food – important counseling point

•Common ADEs:

•Hepatic toxicity (CYP3A4 substrates)

•Diarrhea

•Hypothyroidism

•QT prolongation

•Rash (EGFR TKIs)

•Hand-foot syndrome (EGFR/VEGF TKIs) 

BCR-ABL gene translocation (TKI)

(Philadelphia chromosome)

Imatinib (Gleevec)

Imatinib (Gleevec) indication

chronic myeloid leukemia (CML)

imatinib pharmacogenomics

must be BCR_ABL positive to use

Take with food or within 1 hour after meal to reduce n/v

EGFR (TKI)

Erlotinib (Tarceva), osimertinib (Tagrisso)

Erlotinib (Tarceva), osimertinib (Tagrisso) indication

non-small cell lung cancer (NSCLC)

Erlotinib (Tarceva), osimertinib (Tagrisso) ADE

acneiform rash: development of rash indicates that a patient is expected to have a better response to the drug (avoid sunlight, wear sunscreen, apply topical steroid and antibiotics prophylactically)

Erlotinib: take on empty stomach (with food increases absorption/toxicity risk), DDI with warfarin- increased bleeding risk

Anaplastic Lymphoma Kinase (ALK) TKI

Alectinib, crizotinib, ceritinib, brigatinib

Alectinib, crizotinib, ceritinib, brigatinib indication

NSCLC (~5% NSCLC have ALK mutation)

Alectinib, crizotinib, ceritinib, brigatinib pharmacogenomic

must be ALK mutation positive to use

Alectinib, crizotinib, ceritinib, brigatinib ADE

n/v/d

HER2 and EGFR (TKI)

Lapatinib, neratinib

Lapatinib, neratinib indication

NSCLC, breast cancer

Lapatinib, neratinib pharmacogenomic

must be HER2 positive to use for breast cancer

Lapatinib, neratinib ADE

n/v/d, hand-foot syndrome

Lapatinib, neratinib DDI

DDI with strong CYP3A4 inducers/inhibitors (avoid or dose adjust)

Selective Estrogen Receptor Modulator (SERM)

tamoxifen

Aromatase inhibitor

Letrozole

Antiandrogen

Bicalutamide

Gonadotropin-releasing hormone (GnRH) agonist

Leuprolide