Gastrointestinal Cancer Drug Therapy Flashcards Preview

GI Liver Pharmacology > Gastrointestinal Cancer Drug Therapy > Flashcards

Flashcards in Gastrointestinal Cancer Drug Therapy Deck (58):
1

Anal CANCER INCIDENCE & PROGNOSIS

Uncommon; 4% of lower alimentary tract tumor.
Usually curable.

2

Anal CANCER DRUGS

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

3

Colorectal CANCER INCIDENCE & PROGNOSIS

3rd most common – 2nd most deadly cancer in US.
20% of patients have metastases at diagnosis.

4

Colorectal CANCER DRUGS

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.

5

Esophageal CANCER INCIDENCE & PROGNOSIS

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

6

Esophageal CANCER DRUGS

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

7

Gastric CANCER INCIDENCE & PROGNOSIS

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

8

Gastric CANCER DRUGS

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.

9

GI Carcinoid Tumors CANCER INCIDENCE & PROGNOSIS

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

10

GI Carcinoid Tumors DRUGS

-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

11

Gastrointestinal Stromal Tumors CANCER INCIDENCE & PROGNOSIS

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.

12

Gastrointestinal Stromal Tumors DRUGS

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.

13

Pancreatic CANCER INCIDENCE & PROGNOSIS

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.

14

Pancreatic CANCER DRUGS

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

15

Liver CANCER INCIDENCE & PROGNOSIS

>29,000 new cases of HCC in the US pa; <30%
present with limited-stage disease at diagnosis.

16

Liver CANCER DRUGS

>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.

17

Bevacizumab
MECHANISM

rhuMAb-VEGF

18

Bevacizumab
ISSUES

Bleeding, GI perforation, wound dehiscence, hypertension,
hypersensitivity

19

Capecitabine
MECHANISM

Oral pro-drug metabolized to 5FU

20

Capecitabine
ISSUES

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

21

Cetuximab
MECHANISM

rh/mMAb-EGFR

22

Cetuximab
ISSUES

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

23

Cisplatin
MECHANISM

Forms DNA intrastrand crosslinks & adducts.

24

Cisplatin
ISSUES

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

25

Docetaxel
MECHANISM

Microtubule stabilizer inhibiting depolymerization

26

Docetaxel
ISSUES

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

27

Doxorubicin
MECHANISM

Intercalator, free radical generator, topo II inhibitor

28

Doxorubicin
ISSUES

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

29

Erlotinib
MECHANISM

EGFR-TKI

30

Erlotinib
ISSUES

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

31

Fluorouracil
MECHANISM

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

32

Fluorouracil
ISSUES

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

Gemcitabine
MECHANISM

DNA polymerase inhibitor via incorporation of triphosphate form during DNA synthesis

34

Gemcitabine
ISSUES

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

35

Glutamic Acid
MECHANISM

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

36

Glutamic Acid
ISSUES

Taken orally before meals

37

Imatinib
MECHANISM

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

38

Imatinib
ISSUES

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

39

Interferon-alpha
MECHANISM

Enzyme activation following cell surface receptor binding & tyrosine kinase activation

40

Interferon-alpha
ISSUES

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

41

Irinotecan
MECHANISM

Topo I inhibitor

42

Irinotecan
ISSUES

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

43

Leucovorin
MECHANISM

Reduced folate; modulates the effects of 5-FU

44

Leucovorin
ISSUES

Diarrhea & dehydration

45

Methysergide
MECHANISM

Serotonin inhibitor in GI tract

46

Methysergide
ISSUES

Vasoconstrictor of large &small arteries; used for migraine therapy

47

Mitomycin
MECHANISM

Mono- or bifunctional alkylating agent

48

Mitomycin
ISSUES

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

49

Octreotide
MECHANISM

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

Octreotide
ISSUES

Monitor blood glucose; inhibits insulin and glucagon. Doserelated
diarrhea

51

Oxaliplatin
MECHANISM

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

52

Oxaliplatin
ISSUES

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

53

Sorafenib
MECHANISM

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

Sorafenib
ISSUES

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

Sunitinib
MECHANISM

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

Sunitinib
ISSUES

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

57

Trastuzumab
MECHANISM

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

Trastuzumab
ISSUES

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