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GI Liver Pharmacology > Gastrointestinal Cancer Drug Therapy > Flashcards

Gastrointestinal Cancer Drug Therapy Flashcards

1
Q

Anal CANCER INCIDENCE & PROGNOSIS

A

Uncommon; 4% of lower alimentary tract tumor.

Usually curable.

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2
Q

Anal CANCER DRUGS

A

Radiation therapy alone may lead to a 5-year survival rate in excess of 70%. Radiation + Cisplatin, 5-FU, Mitomycin leads to improved outcomes.

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3
Q

Colorectal CANCER INCIDENCE & PROGNOSIS

A

3rd most common – 2nd most deadly cancer in US.

20% of patients have metastases at diagnosis.

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4
Q

Colorectal CANCER DRUGS

A

5-FU + leucovorin + oxaplatin = FOLFOX
irinotecan instead of oxaplatin = FOLFIRI.
Capecitabine may be used in place of 5-FU.
“Targeted” agents: bevacizumab or cetuximab appear to improve outcomes, except in patients with KRAS mutations.

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5
Q

Esophageal CANCER INCIDENCE & PROGNOSIS

A

~18,000 cases in US pa. Once symptomatic (usually dysphagia), invasion to the muscularis propria is observed & metastasis has occurred.

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6
Q

Esophageal CANCER DRUGS

A

Endoscopic stents for palliation of dysphagia – radiation treatment - chemotherapy for metastatic disease.
Cisplatin + Flurouracil or Cisplatin + 5-FU + Vinblastine.
Taxanes as second-line therapy.

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7
Q

Gastric CANCER INCIDENCE & PROGNOSIS

A

4th most deadly cancer, with a 5-year survival of only 20%

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8
Q

Gastric CANCER DRUGS

A

All patients should be tested for their HER-2 status. HER-2 +: trastuzumab + 5-FU + cisplatin regimen HER-2 -: 5-FU + cisplatin +/- doxorubicin, irinotecan or docetaxel.
Glutamic acid can be used in deficiencies of HCl in the gastric juice.

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9
Q

GI Carcinoid Tumors CANCER INCIDENCE & PROGNOSIS

A

Rare malignancies arisingmfrom cells linking the endocrine & central nervous systems. They originate in cells that are responsible for production
of key neurosecretory hormones.

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10
Q

GI Carcinoid Tumors DRUGS

A

-Octreotide acts at somatostatin receptors to inhibit the secretions. ~12 months regiment because of
tachyphylaxis and/or disease progression.
-IFN-alpha inhibits disease progression & provides symptom relief in ~75% of patients. Drug has substantial adverse effects, including alopecia, anorexia, fatigue, weight loss, fever, a flu-like syndrome, & myelosuppression;
Chemotherapeutics are ineffective

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11
Q

Gastrointestinal Stromal Tumors CANCER INCIDENCE & PROGNOSIS

A

Comprise < 1% of all GI tumors; 3 - 6,000 new
GIST in US pa. GISTs equally distributed across all geographic & ethnic groups & men & women are equally affected. Most patients present between the ages of 50 & 80.

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12
Q

Gastrointestinal Stromal Tumors DRUGS

A

80% are KIT-mutant; 5% are KIT-negative; 5-8% are PDGFRA-mutant; Cytotoxic chemotherapy is futile partly due to P-gp overexpression. TKIs: Imatinib 1st line treatment for nosurgical. Survival now < 2 years to > 5 years. If resistance, developes Sunitinib.

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13
Q

Pancreatic CANCER INCIDENCE & PROGNOSIS

A

Poorly understood cancer of increasing incidence with >44,000 new cases diagnosed in the US pa. Rarely curable; OS <20% of new diagnoses
have organ-confined disease.

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14
Q

Pancreatic CANCER DRUGS

A

Drug management remains controversial +/-surgery/radiation. Frequently, malabsorption & malnutrition.
Drugs include:
Gemcitabine or 5-FU/folinic acid.
Gemcitabine & erlotinib, or FOLFIRINOX [leucovorin-fluorouracilirinotecan-oxiplatin].

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15
Q

Liver CANCER INCIDENCE & PROGNOSIS

A

> 29,000 new cases of HCC in the US pa; <30%

present with limited-stage disease at diagnosis.

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16
Q

Liver CANCER DRUGS

A

> 70% present advanced DZ. ~80% HBV or HCV infections (p53 pathway).
TACE, trans-catheter arterial chemoembolization
Doxorubicin injected tumor is occluded. Arteries feeding tumor spares normal tissue.
Sorafenib is standard for HCC increases overall survival.

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17
Q

Bevacizumab

MECHANISM

A

rhuMAb-VEGF

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18
Q

Bevacizumab

ISSUES

A

Bleeding, GI perforation, wound dehiscence, hypertension,

hypersensitivity

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19
Q

Capecitabine

MECHANISM

A

Oral pro-drug metabolized to 5FU

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20
Q

Capecitabine

ISSUES

A 
Dihydropyrimidine dehydrogenase (DPD) deficiency (familial pyrimidinemia) prevents metabolic activation.
Contraindicated in renal dysfunction; adverse CV events; interacts with oral anticoagulant, coumarin. Neurologic & hematologic toxicities.
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21
Q

Cetuximab

MECHANISM

A

rh/mMAb-EGFR

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22
Q

Cetuximab

ISSUES

A

Cardiac arrest, respiratory arrest, and/or sudden death; infusion reactions. Acneiform rash.

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23
Q

Cisplatin

MECHANISM

A

Forms DNA intrastrand crosslinks & adducts.

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24
Q

Cisplatin

ISSUES

A

Bone marrow suppression, hearing impairment, platinum hypersensitivity, renal failure/ impairment

25
Q

Docetaxel

MECHANISM

A

Microtubule stabilizer inhibiting depolymerization

26
Q

Docetaxel

ISSUES

A

Increased treatment related mortality in NSCLC; edema, contraindicated in hepatic disease; neutropenia, is the dose limiting toxicity

27
Q

Doxorubicin

MECHANISM

A

Intercalator, free radical generator, topo II inhibitor

28
Q

Doxorubicin

ISSUES

A

Bone marrow suppression, heart disease, hepatic disease, secondary malignancies, extravasational necrosis

29
Q

Erlotinib

MECHANISM

A

EGFR-TKI

30
Q

Erlotinib

ISSUES

A

GI toxicity (N/V, diarrhea) prolonged bleeding, elevated LFTs, ocular toxicities; rarely interstitial lung disease

31
Q

Fluorouracil

MECHANISM

A

Pyrimidine antimetabolite that inhibits thymidylate synthase (TS) & interferes with RNA synthesis &
function. Also has some effects on DNA

32
Q

Fluorouracil

ISSUES

A

Severe hematological toxicity including bone marrow suppression. Dihydropyrimidine dehydrogenase (DPD) deficiency (familial pyrimidinemia) lead to enhanced neurotoxicity; enzyme necessary for degrading fluorouracil to
an inactive compound.

33
Q

Gemcitabine

MECHANISM

A

DNA polymerase inhibitor via incorporation of triphosphate form during DNA synthesis

34
Q

Gemcitabine

ISSUES

A

Bone marrow suppression or myelosuppression; infection; sensory peripheral neuropathy; arthralgia, drowsiness, fatigue. N/V, diarrhea, anorexia commonplace; resolve in 2-3 days.

35
Q

Glutamic Acid

MECHANISM

A

Nutritional supplement; used to counterbalance deficiencies of HCl in the gastric juice

36
Q

Glutamic Acid

ISSUES

A

Taken orally before meals

37
Q

Imatinib

MECHANISM

A

Oral TKI as adjuvant treatment following complete resection of Kit (CD117) positive GIST

38
Q

Imatinib

ISSUES

A

GI toxicities (pain, bloating, N/V, constipation, stomatitis, dyspepsia, etc) common. CHF reported in some pts. Neurologic toxicity; fluid retention & edema

39
Q

Interferon-alpha

MECHANISM

A

Enzyme activation following cell surface receptor binding & tyrosine kinase activation

40
Q

Interferon-alpha

ISSUES

A

Neuropsychiatric events including aggression, depression & suicide. Flu-like symptoms: fatigue, fever, malaise, myalgia, arthralgia, chills, headache, & weight loss

41
Q

Irinotecan

MECHANISM

A

Topo I inhibitor

42
Q

Irinotecan

ISSUES

A

Bone marrow suppression, diarrhea; asthenia, fever, pain, weight loss

43
Q

Leucovorin

MECHANISM

A

Reduced folate; modulates the effects of 5-FU

44
Q

Leucovorin

ISSUES

A

Diarrhea & dehydration

45
Q

Methysergide

MECHANISM

A

Serotonin inhibitor in GI tract

46
Q

Methysergide

ISSUES

A

Vasoconstrictor of large &small arteries; used for migraine therapy

47
Q

Mitomycin

MECHANISM

A

Mono- or bifunctional alkylating agent

48
Q

Mitomycin

ISSUES

A

Bone marrow suppression, thrombocytopenia, leukopenia, (HUS) hemolytic-uremic syndrome (microangiopathic hemolytic anemia, thrombocytopenia/irreversible renal failure)

49
Q

Octreotide

MECHANISM

A

Somatostatin analog; reduces duodenal bicarbonate, amylase, reduces gastric acidity, inhibits gallbladder contractility & bile secretion, inhibits meal-induced increases in superior mesenteric artery & portal venous blood flow

50
Q

Octreotide

ISSUES

A

Monitor blood glucose; inhibits insulin and glucagon. Doserelated
diarrhea

51
Q

Oxaliplatin

MECHANISM

A

More potent than cisplatin. The 1,2-diaminocyclohexane carrier thought to contribute to enhanced cytotoxicity & lack of cross-resistance between oxaliplatin & cisplatin

52
Q

Oxaliplatin

ISSUES

A

Dose-limiting neurotoxicity. Thrombocytopenia if used with 5-FU + leucovorin. Diarrhea, N/V, stomatitis

53
Q

Sorafenib

MECHANISM

A

Oral multi-kinase inhibitor targeting serine/threonine & receptor tyrosine kinases in both tumor & vasculature. Targeted kinases include Raf kinase, vascular endothelial growth factor (VEGF) receptors VEGFR-2 and VEGFR-3, platele derived growth factor receptor-β (PDGFR-β), Kit receptor tyrosine kinase (KIT), fms-like tyrosine kinase 3 (FLT-3), & RET

54
Q

Sorafenib

ISSUES

A

Hand-foot skin reaction characterized by redness, pain, swelling, or blisters on the palms of the hands or soles of the feet. Generally appears in first 6-weeks of treatment.

55
Q

Sunitinib

MECHANISM

A

Inhibitor of > 80 receptor tyrosine kinases (RTKs) including platelet derived growth factor receptors
(PDGFRα, PDGRFβ), vascular endothelial growth factor receptors (VEGFR1, VEGFR2, VEGFR3), stem cell factor receptor (KIT), Fms-like tyrosine kinase-3 (FLT3), colony stimulating factor receptor Type 1 (CSR-1R), & the glial cell-line derived neurotrophic factor receptor (RET)

56
Q

Sunitinib

ISSUES

A

Thrombocytopenia and bleeding. QT prolongation, sometimes fatal, gastrointestinal (GI) complications including GI perforation have occurred rarely in patients with intraabdominal malignancies

57
Q

Trastuzumab

MECHANISM

A

HER-2/neu antibody; HER2 is down regulated, cyclin-dependent kinase inhibitor p27 accumulates, & cell cycle arrest occurs. Also inhibits the constitutive HER2 cleavage/shedding mediated by metalloproteases, which may correlate with the clinical activity

58
Q

Trastuzumab

ISSUES

A

LVEF dysfunction & cardiomyopathy. Severe infusion-related reactions including anaphylaxis, angioedema, & pulmonary toxicity; pulmonary toxicity worse in pts with intrinsic lung disease, e.g., COPD, asthma, respiratory insufficiency

GI Liver Pharmacology (9 decks)

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