Treatments Flashcards
Know the treatments for early stage vs metastatic cancers
What are the pharmacological treatments for early-stage breast cancer? What factors must be considered?
Anthracyclines and taxane-based combination of chemotherapy
Consider: HER2 +/- and (ER+ or PR+) or if it is triple negative
ER/PR positive - consider if pre/post menopausal
- Pre-menopausal: tamoxifen, ovarian ablation with goserelin and aromatase inhibitors, oophorectomy
- Post-menopausal: aromatase inhibitors, tamoxifen, fulvestrant
- 5 year treatment following surgery
HER2 negative - AH + paclitaxel
- 4 cycles of doxorubicin and cyclophosphamide every 21 days
- 4 cycles of paclitaxel on days 1, 8, and 12 every 21 days
HER2 positive - TH-FEC
- 3 cycles of docetaxel and trastuzumab every 21 days
- 3 cycles of fluorouracil, epirubicin and cyclophosphamide every 21 days
- 14 cycles of trastuzumab every 21 days
Triple negative - carboplatin + paclitaxel
- followed by anthracyclines
- MAYBE pembrolizumab
What are the pharmacological treatments for metastatic breast cancer? What factors must be considered?
Single-agent chemotherapy
- Taxanes (paclitaxel, docetaxel)
- Anthracyclines (doxorubicin)
- Vinorelbine
- Capecitabine
Consider: HER2 +/- and (ER+ or PR+) or if it is triple negative
ER/PR+ = endocrine therapy first and ongoing
- Pre-menopausal: tamoxifen, ovarian ablation with goserelin and aromatase inhibitors, oophorectomy
- Post-menopausal: aromatase inhibitors, tamoxifen, fulvestrant
HER2 positive - single agent (NOT ANTHRACYCLINES) + trastuzumab and pertuzumab
Triple-negative - single agent + pembrolizumab
What are the pharmacological treatments for localised prostate cancer?
GnRH agonists (goserelin, leuprorelin) and anti-androgens (bicalutamide, flutamide)
- Anti-androgens to prevent flare symptoms (1 month and initiated a few days before injection implant of GnRH agonist)
GnRH antagonist - not available in NZ
- No flare associated
Castrate-resistant: abiraterone
*Chemotherapy NOT standard care
*Radiation therapy required
What are the pharmacological treatments for metastatic prostate cancer?
Chemotherapy - docetaxel, cabazitaxel (taxanes)
Abiraterone if castrate resistant
GnRH + anti-androgen
Enzalutamide, apalutamide, daralutamide
What are the pharmacological treatments for localised colorectal cancer?
Xelox/CapOx - every 3 weeks
- Oxaliplatin + capecitabine 2 weeks on and 1 week off
OR
Folfox - every 2 weeks (IV)
- Oxaliplatin + folinic acid + 5FU bolus and 46 hour infusion
OR
Single-agent capecitabine or 5FU/FA for older/frailer patients
What are the pharmacological treatments for metastatic colorectal cancer?
- Xelox/CapOx - every 3 weeks
- Oxaliplatin + capecitabine 2 weeks on and 1 week off
OR
Folfox - every 2 weeks (IV)
- Oxaliplatin + folinic acid + 5FU bolus and 46 hour infusion
OR
Single-agent capecitabine or 5FU/FA for older/frailer patients
- Single-agent irinotecan (progression)
ALTERNATIVE - chemotherapy in combination with monoclonal antibodies:
1. Bevacizumab
2. Cetuximab
dMMR –> pembrolizumab
What are the pharmacological treatment(s) for small cell lung cancer?
Cisplatin or Carboplatin + etoposide
ADDITION of immunotherapy (atezolizumab or durvalumab), but unfunded
Combined with RT is limited stage
What are the pharmacological treatment(s) for non-small cell lung cancer? (adjuvant treatment - nonmetastatic/advanced)
Cisplatin + vinorelbine
- If EGFR mutation: osimertinib (not funded)
What are the pharmacological treatment(s) for non-small cell lung cancer? (stage III)
Cisplatin + etoposide + RT
- OPTION of 1 year of durvulumab
What are the pharmacological treatment(s) for non-small cell lung cancer? (advanced/metastatic)
Dependant on the mutation or tissue/cell type:
High PD-L1 - pembrolizumab monotherapy
EGFR - osimertinib, erlotinib or gefitinib
ALK: alectinib
ROS-1: crizotinib
EGFR/ALK negative adenocarcinoma: carboplatin + pemetrexed + pembrolizumab x 4 (followed by pembrolizumab + pemetrexed maintenance)
Squamous cell carcinoma: carboplatin + paclitaxel + pembrolizumab x 4 (followed by pembrolizumab maintenance)
What are the pharmacological treatment(s) for early stage melanoma?
Normally surgical removable will cure, however if was stage 3:
Adjuvant 1 year of immunotherapy OR targeted drug therapy
Ipilimumab - improvements seen, but not funded
What are the pharmacological treatment(s) for metastatic melanoma? (local and systemic)
Local treatment:
1. Surgery
2. Radiotherapy
Systemic:
1. Chemotherapy - Alkylating agent –> dacarbazine
2. Immunotherapy - PD-1 inhibitors –> pembrolizumab, nivolumab
3. Targeted therapies (NOT FUNDED) - BRAF inhibitors (Dabrafenib, vemurafenib, encorafenib) or MEK inhibitors (trametinib, cobimetinib, binimetinib)
What are the pharmacological treatment(s) for locally invasive cervical cancer?
Chemotherapy and radiotherapy
Weekly cisplatin with 5 weeks of radiotherapy
What are the pharmacological treatment(s) for metastatic cervical cancer?
Carboplatin + paclitaxel every three weeks
ADDITION of pembrolizumab (unfunded)
Where does breast cancer metastasize? (4 sites)
bone, liver, lungs and brain
Where does prostate cancer metastasize? (1 site)
bone
Where does colorectal cancer metastasize? (2 sites)
liver and lung
Where does lung cancer metastasize? (1 site)
bone
Where does melanoma metastasize? (4 sites)
brain, liver, bone, lung
Where does cervical cancer metastasize? (5 sites)
pelvic area, abdomen, liver, lungs, bone
Comment on the response rate of the following therapies in metastatic melanoma:
1. Chemotherapy
2. Immunotherapy
3. Targeted therapy
Chemotherapy - <20% response rate
Immunotherapy - 30-40% response rate
Targeted therapy - >40% response rate
MoA and ADRs: Alkylating agents (examples + additional notes)
MoA: Formation of azirindyl species that is attacked by nucleophiles (guanine-7) and thereby forms intra- and interstrand cross links. (Adds alkyl groups to nucleic acids, proteins, amino acids and nucleotides)
- There are two Cl molecules that are electrophilic and separate, thus two bonds are able to form, hence crosslinking.
Cell cycle/phase specific = no
Main ADRs: bone marrow depression, nausea and vomiting
Examples:
1. Cyclophosphamide (prodrug that is converted in the liver by CYP P450)
2. Ifosfamide (prodrug that is converted in the liver by CYP P450)
Additional notes: narrow therapeutic index - able to target all cycling cells (including noncancerous)
MoA and ADRs: Anthracyclines (examples)
MoA: intercalates DNA via alkylation of DNA by free radicals and stabilises (inhibits) topoisomerase Ii complex causing strand breakage. This will lead to cell apoptosis.
Cell cycle/phase specific = no
Main ADRs: cardiotoxicity, bone marrow depression, nausea and vomiting, mucositis
Examples:
1. Doxorubicin
2. Daunorubicin
3. Epirubicin
4. Idarubicin
Additional notes: originates from soil in bacteria and is red. therefore can cause staining of bodily fluids
MoA and ADRs: Antimetabolites (examples + additional notes)
MoA: Prevent DNA and RNA synthesis by substituting for essential metabolites
Cell phase specific = S-phase
Main ADRs: toxicity (prevents replication of most cells) –> blood disorders, liver toxicity, respiratory effects
Examples:
1. Folate antagonists
- Methotrexate (inhibits conversion of folic acid to folinic acid via dihydrofolate reductase, FA essential in cell replication)
- Pemetrexed - methotrexate analogue (inhibits multiple enzymes invovled in folate metabolism, including DHFR)
2. Pyrimidine analogues:
- 5-Fluorouracil (acts as a fraudulant nucloetide and inhibits thymidylate synthase, enzyme essential in DNA synthesis)
+ given with folinic acid as it will stabilise 5FU by stabilising complex with thymidylate synthase
Additional notes: Folinic acid is also used as a rescue remedy for large methotrexate doses
