Flashcards in 20 Colorectal Cancer Chan Deck (59):
What is FAP?
Familial Adenomatous Polyposis (FAP). A genetic predisposition. Presence of APC gene mutation, increase polyps, 100% risk for colon cancer by ages 40-50, recommended total colectomy
What is HNPCC?
Hereditary Non-Polyposis Colon Cancer (HNPCC). Presence of mutation in hMLH1 or hMLH2 mismatch repair genes. 70% risk for colon cancer by age 70
Where is most colon cancer found?
Ascending, Sigmoid, Rectum
What is FDA approved to decrease number of polyps in patients with FAP?
What is the preferred screening to be done at age 50?
Annual FOBT (Fecal Occult Blood Test) and FSIG (Flexible Sigmoidoscopy) every 5 years
When is surgery curative for colon cancer?
Stage I, II
When is surgery curative for rectal cancer?
What is the mainstay therapy for Stages I to III Colorectal Cancer?
When is radiation therapy used?
Palliative for unresectable Colon Cancer, pain control. Adjuvant therapy for Stages II, III Rectal Cancer
When is Chemotherapy used?
Standard adjuvant for Stage III Colon Cancer and Stage IV Metastatic Colon Cancer. 5-FU alone based regimens for Stages II, III Rectal Cancer
Which Dukes staging falls under Stage I?
Which Dukes staging falls under Stage II?
Which Dukes staging falls under Stage III?
What is Duke's Stage A?
Indicated penetration into but not through the bowel wall
What is Duke's Stage B?
Indicates penetration through the bowel wall
What is Duke's Stage C?
Indicates lymph node involvement
What is Duke's Stage D?
What does NCCN recommend for Resected Adjuvant Stage II?
5FU/Leucovorin. FOLFOX reasonable for intermediate or high risk Stage II, not for good or average risk
What does NCCN recommend for Resected Stage III?
FOLFOX (repeat every 2 weeks) for 6 months. No indication for targeted therapy
What is in FOLFOX treatment?
Oxaliplatin. Leucovorin. 5FU. Infusional 5FU
What are the general characteristics of Oxaliplatin for Colorectal Cancer?
Increased therapeutic activity and reduced toxicity compared to Cisplatin. Synergistic with 5FU + Leucovorin
What are the side effects of Oxaliplatin?
Acute and chronic neurotoxicity (Acute: peripheral SENSORY neuropathy exacerbated by cold. Chronic: loss of balance, difficulty walking, trouble picking up objects, pain). Nausea and vomiting (Platinum analog; moderate emetogenic risk). Myelosuppression (thrombocytopenia and anemia more common than neutropenia). Nephrotoxicity (less than other 2 platinum)
What is the appropriate antiemetic regimen to use for mFOLFOX?
5HT3 and Steroid. Imend is only for high emetogenic regimens
What are the holding parameters for most cancer treatment?
ANC < 1000 or 1500; Plt < 100k; Hgb < 8.5
What is Oxaliplatin compatible in?
How is Oxaliplatin administered?
Give at same time with IV short infusion as Leucovorin (FOLFOX). Y-site infusion by RNs
What is the difference between the routes of administration for 5FU?
With bolus dosing TS inhibition half life ~10 minutes. Predominant effect of 5FU continuous infusion is binding to TS by FdUMP (i.e. Hand-foot syndrome). Predominant effect of 5FU bolus is incorporation into RNA by FUTP (i.e. Myelosuppression). Infusional 5FU + LV is most efficacious
What is stomatitis management caused by 5FU?
Treat with oral mouthwashes. Good oral hygiene. Avoid alcohol containing mouthwashes
How is hand-food syndrome managed, caused by 5FU?
Avoid wearing tight-fitting shoes and prevent rubbing. Apply emollient cream or ointment. Vitamin B6 may reduce incidence. Grade 4: may require dose interruption, dose reduction, and supportive care measures
What are the most common metastatic sites?
Liver, Lung, Bone, Brain
What are the treatment options for recurrence or metastatic colorectal cancer?
Surgical resection of tumor (if possible). Radiation therapy (palliation of symptoms only). Chemotherapy (recurrence and metastatic)
What is the 1st line NCCN recommended option for advanced metastatic disease?
FOLFOX + Bevacizumab
What is the indication of Irinotecan?
First-line treatment of metastatic colorectal cancer in combination with 5FU/LV +/- Bevacizumab. Single agent second line treatment after failure of 5FU based chemotherapy
What are the side effects with Irinotecan?
Early onset diarrhea. Late onset diarrhea (DLT). Myelosuppression (DLT): Neutropenia. N/V (two drug antiemetic regimen used)
How is Late onset diarrhea by Irinotecan caused?
By direct irritation of GI mucosa by active metabolite SN-38. Dosage should be held for Grade 3 diarrhea (7-9 stools/day)
What is used in the management of Irinotecan-Induced Diarrhea?
Loperamide. 4mg PO loading dose, followed by 2mg PO Q2h ATC. Alternatively: 4mg PO Q4h ATC (better for sleeping). Continue until diarrhea-free for 12 hours. Max dose = 16mg/day
What are the pharmacogenetics to look for with Irinotecan?
Increase neutropenia risk in patients with reduced activity in the drug-metabolizing enzyme 1A1 (UGT1A1). A molecular assay is now available for the UGT1A1*28 allele
What is the DDI between Irinotecan and St. Johns Wort?
Shown to decrease the efficacy of Irinotecan by inhibiting the metabolism of Irinotecan to its active metabolites SN-38
When is Capecitabine (Xeloda) indicated?
For first-line treatment of metastatic colorectal cancer when treatment of 5FU alone is preferred or in adjuvant setting for Stage III colon cancer. Xeloda equivalent to 5FU/LV
What are the side effects with Capecitabine?
Diarrhea (DLT). Mucositis. Loss of appetite. Dehydration. N/V (low emetogenic risk). Myelosuppression (less than IV bolus 5FU). Hand-foot syndrome
What is a DDI to look out for with Capecitabine?
Warfarin - increased INR (monitor closely, INR can fluctuate depending on Capecitabine dosing schedule)
How should Capecitabine be taken?
Take dose w/in 30 minutes after a meal. Swallow tablets only with water
For targeted therapy, what are the Anti-EGFR agents (KRAS wild-type only) used?
Cetuximab (Erbitux). Panitumumab (Vectibix)
For targeted therapy, what are the Anti-VEGF agents used?
Bevacizumab (Avastin). Ziv-Aflibercept (Zaltrap)
What is the rationale for EGFR Blockade?
EGFR is expressed in a significant percent of solid tumors. EGFR expression has been reported to be an indicator of poor prognosis, decreased survival, and increased metastases in breast, lung, colon, and other tumor types
What is the EGFR K-ras genotype?
K-ras is a gene that codes for a protein that plays an important role downstream of the EGFR in the signaling pathway. 2 types - normal or non-mutated (wild type) or mutated. Mutated gene is constitutively activated resulting in continuous signaling independent of EGFR activation
When is Cetuximab (Erbitux) indicated?
As a combination with Irinotecan or alone if cannot tolerate Irinotecan. Effective against CRC with wild-type. NOT effective against mutated K-ras tumors
What are the more common ADRs with Cetuximab (Erbitux)?
Acneiform rash!!! Dry skin, tiredness or weakness, fever, hypomagnesemia, constipation, and abdominal pain
How can the ADRs with Cetuximab (Erbitux) be reduced?
Pre-medicate with antihistamine type medication - Diphenhydramine IV initial infusion
What can be done for Acneiform rash/pruritis?
Treatment with any anti-acne medication. Choose a non-alcohol containing agent. Clindamycin Topical Gel. Doxycycline 100mg PO BID if need systemic treatment
When is Panitumumab (Vectibix) indicated?
Approved for use in colorectal cancer patients that have FAILED standard therapy. K-ras wild-type REQUIRED. No pre-medication is required and less infusion reactions reported than Cetuximab
When is Bevacizumab (Avastin) used?
In combination with 5FU based chemotherapy with advanced/metastatic disease. Anti-VEGF agent
What are the ADRs with Bevacizumab (Avastin)?
Hypertension, proteinuria! Pain, asthenia, diarrhea, and leukopenia. No need to premedicate, infusion reaction rare
What are the serious ADRs with Bevacizumab (Avastin)?
GI perforations, wound healing, complications
What is HTN like with Bevacizumab (Avastin)?
Can result in hospitalization or discontinuation of therapy. Treat with thiazide diuretics, ACE-I, CCBs. Monitor blood pressure at least every 2-3 weeks prior to each treatment
What is Proteinuria like with Bevacizumab (Avastin)?
Monitor with serial urinalysis (UA protein > 2g, require 24 hours urine collection, resume only if urine protein < 2g)
What is a BBW with Bevacizumab (Avastin)?
Bleeding. Surgery, dental procedures, nose bleeds. Bevacizumab (Avastin) should not be given for at least 28 days following surgery and incisions should be completely healed before starting Avastin therapy. GI perforations/wound healing complications
When does NCCN recommend Ziv-Aflibercept (Zaltrap)?
Zaltrap + FOLFIRI (patients resistant to or progressed on Oxaliplatin-based regimen) - 2nd line