lung and colorectal

NSCLC Staging and general treatment

• Stage I: no lymph node involvement

  • Surgery +/- radiation

• Stage II: lymph node involvement

  • Surgery + adjuvant chemotherapy +/- radiation

• Stage IIIA: early-stage

  • surgery, radiation, and pharmacotherapy

• Stage IIIB: Advanced disease, usually unresectable

  • Chemoradiation + adjuvant chemotherapy +/- targeted agents

• Stage IV: Advanced disease, unresectable tumor

  • Chemotherapy and radiation

Metastatic or recurrent disease (treatment failure) is based on biomarkers

EGFR TKIs

osimertinib, erlotinib

EGFR TKI ADE

•Common: acneiform rash, diarrhea, anorexia, fatigue

•Rare/Severe: Interstitial lung disease

Erlotinib clinical pearls

•take on empty stomach (with food increases absorption/toxicity risk)

•DDI with warfarin- increased bleeding risk 

ALK TKIs

alectinib, crizotinib (both orally administered)

ALK TKI ADE

•Common: leukopenia, fatigue, hepatotoxicity

•Rare/Severe: Interstitial lung disease

PD-1 or PD-L1 inhibitors

pembrolizumab, ipilimumab, nivolumab, atezolizumab, durvalumab

PD-1 or PD-L1 inhibitors MOA

•cancer cells try to evade the immune system by overexpressing PD-L1. PD-1 or PD0L1 inhibitors allows the T cells to remain active and destroy cancer cells.

PD-1 or PD-L1 inhibitors ADE

•Immune related toxicities: colitis, hepatitis, pulmonary toxicity (pneumonitis), nephrotoxicity, thyroid disorders, myocarditis, encephalitis, endocrinopathies (hyperglycemia), fatigue 

•Immune related toxicities may require interruption or permanent discontinuation of treatment, also treated with steroids

Common lung cancer chemotherapy regimens

•cisplatin plus gemcitabine x 4-6 cycles

•(cisplatin or carboplatin) plus etoposide × 4-6 cycles

•(cisplatin or carboplatin) plus pemetrexed +/- pembrolizumab x 4 cycles

•(cisplatin or carboplatin) plus paclitaxel +/- pembrolizumab x 4 cycles

SCLC Treatment

• Initially very sensitive to chemotherapy and radiation, response rate up to 90%

  • Cisplatin-etoposide with concurrent radiation best clinical data for limited stage

• Patients with extensive disease should have immunotherapy (atezolizumab or durvalumab) added to chemotherapy

  • Carboplatin or cisplatin + etoposide + durvalumab x 4-6 cycles

  • Carboplatin or cisplatin + etoposide + atezolizumab x 4-6 cycles

• If the patient achieves a complete remission from concurrent chest radiation and chemotherapy, prophylactic cranial irradiation (PCI) is recommended because the development of brain metastases is greater than 30% for SCLC.

colorectal cancer screening

• Age: begin at 45 years old for average risk people

• Methods:

  • Stool test: fecal immunochemical testing (FIT)

    • Looks for presence of blood in stool

  • Structural examination: Colonoscopy

    • Requires extensive bowel preparation and procedural sedation

    • Examines entire colon and rectum, can remove adenomatous polyps during procedure

• Frequency:

  • FIT test: annually

  • Colonoscopy: every 10 years (can be more often if increased risk

CRC Treatment Overview

•Stage I: surgery

•Stage II: surgery +/- adjuvant chemotherapy

•Stage III: surgery + adjuvant chemotherapy

•Stage IV:

• +/- neoadjuvant chemotherapy + surgery

• chemotherapy

Common CRC chemotherapy regimens

•CAPEOX: capecitabine, oxaliplatin

•FOLFOX:  leucovorin, oxaliplatin, 5-fluorouracil

•FOLFIRI: leucovorin, fluorouracil, irinotecan

•FOLFIRINOX: leucovorin, fluorouracil, irinotecan, oxaliplatin

Leucovorin roles

•Leucovorin is folinic acid (‘FOL’ in regimens)

•Leucovorin reduces toxicity for high dose methotrexate

•Reduces toxicity by providing a source of folic acid to healthy cells

•Started 24 hours after last dose of methotrexate

•Low dose: 15mg IV/PO Q6 hours x 3 days

•Leucovorin enhances cytotoxicity for fluorouracil

•Given alone, fluorouracil has short half life, adding leucovorin improves the binding of 5FU to an enzyme within cancer cell and increases half life

•Also increases ADEs (mucositis, hand/foot syndrome/diarrhea)

•High dose: 400mg/m² given concurrently with 5-FU over 2-hour infusion

VEGF mAbs

bevacizumab

bevacizumab MOA

inhibits angiogenesis, an important step in tumor growth

bevacizumab ADE

infusion related reactions, hypertension, bleeding, thromboembolism, impaired wound healing, proteinuria, GI perforation

bevacizumab pearl

Wait until at least 4-6 weeks after surgery to initiate (to allow wound healing) 

EGFR mAbs

cetuximab, panitumumab

EGFR mAb MOA

inhibits of cell growth, induces of apoptosis

EGFR mAbs ADE

infusion related reactions, acneiform rash, electrolyte abnormalities

EGFR mAb PGx

test for EGFR and KRAS gene expression, must be KRAS wild type to use

Rectal Cancer

Similar therapies as colon cancer (surgery and chemotherapy) except for emphasis on radiation or chemoradiation (chemotherapy + radiation) as standard modality in treatment