ON13 Colorectal cancer

NZ stats:
- Eight New Zealander’s diagnosed each day​
- ❌ New Zealander’s die from bowel cancer each day​
- ❌ cause of cancer death in New Zealand​
- One of the highest rates in the ❌ ​
- Rates for ❌ are highest in world ​
- Less frequent in ❌ vs. non-Maori

Risk factors for colorectal cancer:
❌ sex​
Age​ (older)
History of colorectal cancer, ❌
Inherited factors (e.g. familial adenomatous polyposis, ❌)​
Lifestyle factors​
Diet (❌ meat, processed food, high fat, low fibre)​
Physical ❌​
Long term ❌​
Excessive ❌​
Obesity

Protective Factors​:
Some evidence ❌ use (13-28% RRR)​
❌ hormone use (RRR 35%)​
Healthy BMI, physical ❌, smoking ❌​
Fibre, fruits, vegetables, reduced meat consumption​
❌ supplementation​

Screening usually starts at age 50​. Decreases mortality through early detection​.
Methods:​
❌ (every 10 years post-50)​
Flexible ❌ (every 5 years)​
CT scan (every 5 years)​
Double contrast ❌ (every 5 years)​
Fecal occult blood tests (❌)​

Diagnosis:
History and physical exam​
Colonoscopy ❌ sigmoidoscopy​
❌ (to confirm presence of cancer)​
❌ scanning (search for metastases)​
Baseline ❌ (CBC, platelet, liver panel, renal panel, CEA, iron studies)​
Pathological staging after tumor resection (❌)​
Gene mutation testing (?)​

Staging:
Stage 1 - tumour size T1 (no deeper than ❌) and T2 (❌)
Stage 2 - T3 (❌ muscularis)
Stage 3 - N1 (❌ lymph nodes involved), N2 (❌ lymph nodes involved)
Stage 4 - M - ❌ metastases.

Clinical factors associated with poor prognosis:​
Bowel ❌
High preoperative ❌
Distant ❌​
Location of tumor in ❌ area​
Molecular markers (KRAS mutations MSI, BRAF mutations)​

Treatment:
Need to consider stage, performance status, patient preferences, comorbidities, age. Curability depends on tumor stage​.
General approach:​
❌ of primary tumor is 1st line therapy (Stage 1, 2, 3)​
Removal of tumor plus ❌ of tumor free bowel and regional ❌ for cure​
Adjuvant ❌ can be given to eliminate residual micrometastases ​

if it's metastases (Stage 4)​?
Classified as resectable, potentially resectable, or unresectable​
❌ is mainstay, radiation may be used for palliative purposes​

Adjuvant Systemic Chemotherapy​:
Goal: reduce risk of recurrence and overall mortality in Stage ❌​. (Little to no benefit from Stage ❌, no benefit in Stage ❌​.)
Duration: ❌ months​
Choice of regimen based on toxicity and convenience​. Typically based on ❌ (both with ❌)​.

Leucovorin(Folinic acid), fluorouracil and oxaliplatin aka FOLFOX side effects:
- neutropenia, therefore ❌
- anaemia, therefore breathlessness and ❌
- potentially reversible ❌ neuropathy
- nausea
- diarrhoea
- muscositis
- rarely heart problems

CAPOX (capecitabine and oxaliplatin) side effects:
- neutropenia, therefore infections
- anaemia, therefore breathlessness and weakness
- potentially reversible peripheral ❌
- nausea
- diarrhoea OR ❌
- muscositis
- ❌ syndrome
- rarely tinnitus, heart problems,

Rectal Cancer​
- Poorer outcomes. ​Difficult to ❌, propensity for ❌.
- Most patients with Stage II or III should receive ❌ radiation and chemotherapy ❌operatively ​
- ❌ chemotherapy and radiation for Stage II or III​
- Adjuvant for 6 months post-surgery​
- Same regimens as indicated or colorectal (e.g. FOLFOX or CapeOx)​

Colorectal – Metastatic Disease​:
- If resectable, surgery is indicated (most commonly ❌)​. Neoadjuvant ❌ adjuvant chemotherapy​ for patients with metastatic disease ❌ to liver or lung​. FOLFOX, FOLFIRI, FOLFOXIRI, CapOx​.
- Unresectable​ - Chemotherapy (e.g. FOLFOX, CapOx, FOLFIRI)​ only. Goal is to control ❌ and prolong survival.​
Role for ❌ therapy (bevacizumab) [inhibits VEGF]​ & EGFR inibitors (cetuximab, panitumumab) [for patients with wild-type RAS tumors)​

A note about Irinotecan… ​
Evidence exists for metastatic disease​!
Improved overall ❌ vs. 5FU/LV alone​ :-)
Combination with 5FU/LV +/- oxaliplatin may improve ❌ of metastases and improve patient survival .
Must monitor for ❌​.

Data in adjuvant setting (non-metastatic disease) lacking​...

Oral Capecitabine:
May be commonly seen in community pharmacy​.
Caution in: ❌ electrolyte disturbance, ❌ conditions.
Avoid in ❌ impairment​.
Dose reductions if CrCl ❌ml/min, avoid ❌ml/min ​.
Contraceptive advice ❌ for child-bearing aged females​.
Potential ADRs: ​ hand-foot syndrome, diarrhea, ❌ (rare), ❌ skin conditions (very rare)​