GI Cancer - Geffen Flashcards
What are adjuvant and neoadjuvant treatments?
Adjuvant- curative -after surgery of primary tumor when there are no metastases on clinical or imaging exam. Evidence showed 6 months of chemo after surgery decreases death and recurrence.
Neoadjuvant- curative- before surgery when there are no metastases on clinical or imaging exam.
Palliative- when metastases are found on clinical or imaging exam.
Esophageal cancer:
What are the types common?
What is the treatment?
Histology: squamous
adenocarcinoma
surgery (many unfit or undesiring) or chemoradiation therapy can cure some patients. Combination of radiotherapy and chemo can cure some patients.
Palliation
esophageal stent placed by endoscope
Radiotherapy- without surgery or chemo
chemotherapy : 5FU (not so toxic on its own) continuous over 5 days plus cisplatin on day 1 every 4 wks
What is the treatment for gastric cancer?
Surgery for localized cancer (often involves stomach removal, still can come back)
Bulky disease in stomach, no mets-
neoadjuvant plus adjuvant chemotherapy (European)
adjuvant chemoradiotherapy-(US)
Metastatic disease- chemotherapy for palliation- for good performance status pts
Continuous IV 5FU(or oral capecitabine) +cisplatin+ epirubicin
Docetaxel + continuous 5FU +/- cisplatin
Investigational (oxaliplatin and other agents)
If not operated on, may have GI bleeding
Radiotherapy for palliation-kills enough cells to stop bleeding
Biologic Therapy for Gastric Cancer: Monoclonal Antibodies
For HER-2 (Human Epidermal Growth Cell Receptor- overstimulated proliferation in cancer) over expressing patients (a small fraction of all gastric cancer patients), trastuzumab (Herceptin™) is added to chemotherapy.
Clinical trials are investigating the role of bevacizumab (Avastin™) , cetuximab and other agents.
Also used for palliation with chemo over chemo alone.
Gastric lymphoma: types and therapy
MALT (mucosa associated lymphoid tissue) tumors (lymphomas rare anywhere but the stomach)
Treat heliobacter pyloris infection (often precipitating factor)
Chemotherapy
radiotherapy
Diffuse large B-cell lymphoma
Stage I: 3 cycles CHOP chemotherapy + rituximab (anti-CD-20 antibody)+ radiotherapy
Stage II-IV: 6 or more cycles CHOP +rituximab
CHOP =
C= cyclophosphamide
H= doxorubicin (hydroxydaunorubicin)
O= vincristine (Oncovin)
P= prednisone
Hepatocellular cancer:
Where is it most common, what are associated diseases?
What are the treatments?
More common in developing world than in developed nations-especially in Asia
Major cause - hepatitis B and C
Associated with cirrhosis (In Hep B carriers cancer develops before cirrhosis)
Surgery is the only curative treatment-partial hepatectomy (no chemo)
Intra-arterial embolization can reduce the size of tumor and improve pain control.
Radiofrequency ablation- percutaneous or intraoperative - CT with needles
Radiation therapy to liver-palliation. - shrinks tumor
Spreads locally more than diffuse metastasis
Chemo is effective in shrinkin ghepatoblastomas ONLY in children
Liver transplantation-for tumors smaller than 5 cm with no portal vein or vena caval involvement.
Fibrolamellar histology- best prognosis
5yr survival: 20-36 %
Problems: shortage of donor livers, cost, morbidity and mortality
Biologic Drug Therapy in Hepatocellular Cancer
Tyrosine kinase inhibitor: sorafenib- oral.
Enters cell and inhibits multiple pathways within cell.
Side effects: hypertension, nausea, bleeding,fatigue,cardiac dysfunction(unusual)
p.o. 400 mg bid
Llovet et al NEJM 359:378,2008
600 pts- inop- randomized placebo or sorafinib
Overall survival-10.7 mo-sorafinib, 7.9 mo placebo
Hazard rate 0.69.
Average 3 months longer.
Pancreatic cancer
treatment
Surgery for cure (unusual)
with adjuvant chemotherapy- gemcitabine based- recent evidence of benefit.
Chemotherapy followed by chemoradiotherapy for locally advanced disease- sometimes followed by surgery (after it shrinks)
Chemotx- palliation of metastatic disease
Most common is adenocarcinoma.
Neuroendocrine tumors of pancreas are treated differently.
Chemo:
Gemcitabine +/- biologic tx(erlotinib)
IV infusion over 30 minutes weekly
pyrimidine antagonist
FOLFIRINOX
5FU-leucovorin (reduced folate-chemoprotectant)
Oxaliplatin
Irinotecan
Relatively toxic, just for fit patients, more harsh
Gall bladder:
Treatment
Often found unexpectedly/incidentally at time of cholecystectomy for benign disease.
Surgery is the only curative modality
Radiation therapy is often given after surgery if the disease has penetrated through the gall bladder wall.
Cholangiocarcinoma/ Biliary Cancer
Tumor of the bile duct
Present with jaundice
Treatment for cure- surgery
Palliation-biliary drainage or bypass as needed
Chemotherapy with cisplatin + gemcitabine
Small intestine cancer:
Proportion of GI cancers
Types of cancer
Where?
Treatment
Only 1-3 % of all GI malignancies are of small bowel origin - rare
Adenocarcinoma-mainly in duodenum (50% of small bowel tumors)
Carcinoid-ileum (low grade neuroendocrine tumor)
Lymphoma- ileum and jejunum
Sarcoma- throughout,more in ileum - rare
Surgery
Lymphoma- chemotherapy: CHOP (plus rituximab-antiCD20Ab if B-cell)
Colon cancer
treatment
risk factors
Surgery
When no spread beyond regional nodes
Even with metastases, to relieve obstruction or bleeding
For resectable liver metastases
For resectable lung, ovarian metastases
Adjuvant chemotherapy in some patients when no metastases detected. Given when risk of recurrence is high enough.
Metastases-chemotx and biologic therapy
Liver metastases –treat like liver cancer: palliation with cryotherapy, radiofrequency ablation.
Sometimes resection of liver mets.
Adjuvant:
(DeGramont regimen) 5-FU continuous over 2 days with additional rapid infusions of 5FU and leucovorin each day. (every 2 weeks)
FOLFIRI: DeGramont+ irinotecan
FOLFOX: DeGramont + oxaliplatin
Weekly 5-FU-leucovorin(Roswell Park)
Chemo:
FOLFIRI
FOLFOX
Weekly infusions of 5FU-leucovorin
UFT, capecitabine(Xeloda-oral 5FU, not so available)
Xeloda plus oxaliplatin (XELOX)
Xeloda plus ininotecan (XELIRI)
FOLFOX + bevacizumab
Irinotecan + cetuximab
Pathological stage (based on depth)- only surgery for stage I (mucosa and submucosa only) Clinical-path features: young age, high serum carcinoembryonic antigen (CEA), obstruction are among risk factors for later metastasis Presence of microsatellite instability(MSI) on immunohistochemical staining or MMR-D/MSI-H but better survival with resected colon in these patients Gene expression- OncotypeDX™-Uses PCR with 12 genes-7 tumor, 5 control, formula developed to determine chance of relapse
Patients with KRAS mutation will not respond to EGFR antibody treatment because they are constiuitively on.
Chemotherapy drug properties:
5-Fluorouracil (5-FU)
Capecitibine (Xeloda)
Tegafur-uracil (UFT)
Irinotecan (CPT-11)
Oxaliplatin
Prevents DNA production by fluoronation.
Anti-metabolite: pyrimidine analog -FdUTP and FUTP incorporated into DNA and RNA respectively
IV push, continuous infusion, intraarterial
most active during DNA synthesis (S phase)
Capecitibine is a prodtrug of 5-FU activated by thymidine phosphorylase which is more active in the tumor so it is more selective.
UFT is converted to 5-FU in the liver, uracil inhibits its degradation.
Irinotecan: semisynthetic derivative of plant alkaloid, campothecin
Inhibits topoisomerase I, preventing resealing of DNA breaks. Important for DNA separation.
Oxaliplatin: Platinum compound-Contains DACH (diaminocylohexane) –forms DNA adducts (attachment of DNA and platinum) that leads to cell death. Major toxicity: neuropathy. Also- cold induced laryngopharyngeal spasm.
Antibody therapy in colon cancer
cetuximab- anti-EGFR (epidermal growth factor receptor, =HER1) chimeric (human/mouse) antibody.
Bevacizumab (Avastin®): anti-VEGF (vascular endotherlial growth factor) chimeric antibody.
Panitumumab- anti-EGFR antibody- fully humanized
Rectal cancer
treatment
Multimodal therapy for many patients – surgery with neoadjuvant(preop) and adjuvant (postop) chemotherapy
Chemoradiotherapy (continuous 5-FU during radiotx) followed by surgery followed by adjuvant chemotherapy
Local excision for small low grade tumors without deep penetration
Rectum has no serosa so spreads more easily, treatment is similar to colon cancer but no conservative option
