Gastrointestinal Cancer Drug Therapy Flashcards
Anal CANCER INCIDENCE & PROGNOSIS
Uncommon; 4% of lower alimentary tract tumor.
Usually curable.
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.
Colorectal CANCER INCIDENCE & PROGNOSIS
3rd most common – 2nd most deadly cancer in US.
20% of patients have metastases at diagnosis.
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.
Esophageal CANCER INCIDENCE & PROGNOSIS
~18,000 cases in US pa. Once symptomatic (usually dysphagia), invasion to the muscularis propria is observed & metastasis has occurred.
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.
Gastric CANCER INCIDENCE & PROGNOSIS
4th most deadly cancer, with a 5-year survival of only 20%
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.
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.
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
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.
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.
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.
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].
Liver CANCER INCIDENCE & PROGNOSIS
> 29,000 new cases of HCC in the US pa; <30%
present with limited-stage disease at diagnosis.
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.
Bevacizumab
MECHANISM
rhuMAb-VEGF
Bevacizumab
ISSUES
Bleeding, GI perforation, wound dehiscence, hypertension,
hypersensitivity
Capecitabine
MECHANISM
Oral pro-drug metabolized to 5FU
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.
Cetuximab
MECHANISM
rh/mMAb-EGFR
Cetuximab
ISSUES
Cardiac arrest, respiratory arrest, and/or sudden death; infusion reactions. Acneiform rash.
Cisplatin
MECHANISM
Forms DNA intrastrand crosslinks & adducts.
Cisplatin
ISSUES
Bone marrow suppression, hearing impairment, platinum hypersensitivity, renal failure/ impairment
Docetaxel
MECHANISM
Microtubule stabilizer inhibiting depolymerization
Docetaxel
ISSUES
Increased treatment related mortality in NSCLC; edema, contraindicated in hepatic disease; neutropenia, is the dose limiting toxicity
Doxorubicin
MECHANISM
Intercalator, free radical generator, topo II inhibitor
Doxorubicin
ISSUES
Bone marrow suppression, heart disease, hepatic disease, secondary malignancies, extravasational necrosis
Erlotinib
MECHANISM
EGFR-TKI
Erlotinib
ISSUES
GI toxicity (N/V, diarrhea) prolonged bleeding, elevated LFTs, ocular toxicities; rarely interstitial lung disease
Fluorouracil
MECHANISM
Pyrimidine antimetabolite that inhibits thymidylate synthase (TS) & interferes with RNA synthesis &
function. Also has some effects on DNA
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.
Gemcitabine
MECHANISM
DNA polymerase inhibitor via incorporation of triphosphate form during DNA synthesis
Gemcitabine
ISSUES
Bone marrow suppression or myelosuppression; infection; sensory peripheral neuropathy; arthralgia, drowsiness, fatigue. N/V, diarrhea, anorexia commonplace; resolve in 2-3 days.
Glutamic Acid
MECHANISM
Nutritional supplement; used to counterbalance deficiencies of HCl in the gastric juice
Glutamic Acid
ISSUES
Taken orally before meals
Imatinib
MECHANISM
Oral TKI as adjuvant treatment following complete resection of Kit (CD117) positive GIST
Imatinib
ISSUES
GI toxicities (pain, bloating, N/V, constipation, stomatitis, dyspepsia, etc) common. CHF reported in some pts. Neurologic toxicity; fluid retention & edema
Interferon-alpha
MECHANISM
Enzyme activation following cell surface receptor binding & tyrosine kinase activation
Interferon-alpha
ISSUES
Neuropsychiatric events including aggression, depression & suicide. Flu-like symptoms: fatigue, fever, malaise, myalgia, arthralgia, chills, headache, & weight loss
Irinotecan
MECHANISM
Topo I inhibitor
Irinotecan
ISSUES
Bone marrow suppression, diarrhea; asthenia, fever, pain, weight loss
Leucovorin
MECHANISM
Reduced folate; modulates the effects of 5-FU
Leucovorin
ISSUES
Diarrhea & dehydration
Methysergide
MECHANISM
Serotonin inhibitor in GI tract
Methysergide
ISSUES
Vasoconstrictor of large &small arteries; used for migraine therapy
Mitomycin
MECHANISM
Mono- or bifunctional alkylating agent
Mitomycin
ISSUES
Bone marrow suppression, thrombocytopenia, leukopenia, (HUS) hemolytic-uremic syndrome (microangiopathic hemolytic anemia, thrombocytopenia/irreversible renal failure)
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
Octreotide
ISSUES
Monitor blood glucose; inhibits insulin and glucagon. Doserelated
diarrhea
Oxaliplatin
MECHANISM
More potent than cisplatin. The 1,2-diaminocyclohexane carrier thought to contribute to enhanced cytotoxicity & lack of cross-resistance between oxaliplatin & cisplatin
Oxaliplatin
ISSUES
Dose-limiting neurotoxicity. Thrombocytopenia if used with 5-FU + leucovorin. Diarrhea, N/V, stomatitis
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
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.
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)
Sunitinib
ISSUES
Thrombocytopenia and bleeding. QT prolongation, sometimes fatal, gastrointestinal (GI) complications including GI perforation have occurred rarely in patients with intraabdominal malignancies
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
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
