Flashcards in Gastrointestinal Cancer Drug Therapy Deck (58):
Anal CANCER INCIDENCE & PROGNOSIS
Uncommon; 4% of lower alimentary tract tumor.
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.
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.
Bleeding, GI perforation, wound dehiscence, hypertension,
Oral pro-drug metabolized to 5FU
Dihydropyrimidine dehydrogenase (DPD) deficiency (familial pyrimidinemia) prevents metabolic activation.
Contraindicated in renal dysfunction; adverse CV events; interacts with oral anticoagulant, coumarin. Neurologic & hematologic toxicities.
Cardiac arrest, respiratory arrest, and/or sudden death; infusion reactions. Acneiform rash.
Forms DNA intrastrand crosslinks & adducts.
Bone marrow suppression, hearing impairment, platinum hypersensitivity, renal failure/ impairment
Microtubule stabilizer inhibiting depolymerization
Increased treatment related mortality in NSCLC; edema, contraindicated in hepatic disease; neutropenia, is the dose limiting toxicity
Intercalator, free radical generator, topo II inhibitor
Bone marrow suppression, heart disease, hepatic disease, secondary malignancies, extravasational necrosis
GI toxicity (N/V, diarrhea) prolonged bleeding, elevated LFTs, ocular toxicities; rarely interstitial lung disease
Pyrimidine antimetabolite that inhibits thymidylate synthase (TS) & interferes with RNA synthesis &
function. Also has some effects on DNA
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.
DNA polymerase inhibitor via incorporation of triphosphate form during DNA synthesis
Bone marrow suppression or myelosuppression; infection; sensory peripheral neuropathy; arthralgia, drowsiness, fatigue. N/V, diarrhea, anorexia commonplace; resolve in 2-3 days.
Nutritional supplement; used to counterbalance deficiencies of HCl in the gastric juice
Taken orally before meals
Oral TKI as adjuvant treatment following complete resection of Kit (CD117) positive GIST
GI toxicities (pain, bloating, N/V, constipation, stomatitis, dyspepsia, etc) common. CHF reported in some pts. Neurologic toxicity; fluid retention & edema
Enzyme activation following cell surface receptor binding & tyrosine kinase activation
Neuropsychiatric events including aggression, depression & suicide. Flu-like symptoms: fatigue, fever, malaise, myalgia, arthralgia, chills, headache, & weight loss
Topo I inhibitor
Bone marrow suppression, diarrhea; asthenia, fever, pain, weight loss
Reduced folate; modulates the effects of 5-FU
Diarrhea & dehydration
Serotonin inhibitor in GI tract
Vasoconstrictor of large &small arteries; used for migraine therapy
Mono- or bifunctional alkylating agent
Bone marrow suppression, thrombocytopenia, leukopenia, (HUS) hemolytic-uremic syndrome (microangiopathic hemolytic anemia, thrombocytopenia/irreversible renal failure)
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
Monitor blood glucose; inhibits insulin and glucagon. Doserelated
More potent than cisplatin. The 1,2-diaminocyclohexane carrier thought to contribute to enhanced cytotoxicity & lack of cross-resistance between oxaliplatin & cisplatin
Dose-limiting neurotoxicity. Thrombocytopenia if used with 5-FU + leucovorin. Diarrhea, N/V, stomatitis
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
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.
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)
Thrombocytopenia and bleeding. QT prolongation, sometimes fatal, gastrointestinal (GI) complications including GI perforation have occurred rarely in patients with intraabdominal malignancies
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