Surgery/Radiation
The following treatment Modalities are used in the management of SCLC
Surgery, Radiation therapy, Systemic Therapy
What are the three types of Chemo?
1. Platinum agents
2. Topoisomerase inhibitors
3. Akylating agents
What enzymes make small cuts in the DNA strands to relieve the tightly wound tension?
Topoisomerases
What is immunotherapy?
Use of medications that stimulate the immune system to help the body fight cancer.
Immune checkpoints are normally used by the body to regulate the intensity of immune responses.
NCCN Guidelines are based on?
Robust scientific evidence and/or clinical expertise that is beyond FDA approved indications "Off Label Use"
*Fatal Cancers-off label use is common
Surgery is reserved for which Stage?
Limited-stage SCLC and select patients with T3, N0 SCLC
*accompanied by lymph node removal to assess cancer spread to nodes
*usually followed by adjuvant therapy (radiation and/or systemic therapy)to target any remaining cancer cells
What are the most common Platinum agents used?
1. Cisplatin
2. Carboplatin
What are the most common Topoisomerase I inhibitors used?
and
What is the most commonly used topoisomerase II used?
Topoisomerase I: Irinotecan and topotecan
Topoisomerase II: Etoposide
Which Check Point Inhibitors are FDA-approved for SCLC and are monoclonal antibodies (mAbs) directed against PD-L1?
1. Atezolizumab (Tecentriq): 2019 FDA approved for ES-SCLC, IV, in cobination for carboplatin and etoposide for first-line treatment of adults patients w/ES-SCLC
2. Durvalumab (Imfinzi): 2020 FDA approved for ES-SCLC, IV, in combo w/etoposide and either carboplatin or cisplatin for first-line treatment of adult patients with ES-SCLC
NCCN Categories of Evidence & Consensus?
Category 1: Based upon high-level evidence, uniform NCCN consensus that the intervention is appropriate
Category 2A: Based upon lower-level evidence, is uniform NCCN consensus that the intervention is appropriate
Category 2B: Based upon lower-level evidence, there is NCCN consensus that the intervention is appropriate
Category 3: Based upon any level of evidence, there is major NCCN disagreement that the intervention is appropriate
What are the 4 types of surgery?
1. Wedge:removal of small wedge
2. Segmentectomy: removal larger segment
3. Lobectomy: Removal of entire lobe
4. Pneumonectomy: removal of entire lung
What agents are considered standard of care for first line treatment of both LS-SCLC and ES-SCLC?
Platinum agents
Alkylating agents directly bing to DNA and introduce a chemical group called?
and
What two actions do alkylating agents trigger that eventually lead to inhibition of ?
1. Aklyl Group
2. Cell Cycle and Cell death
PD-1 and PD-L1 agents, called checkpoint inhibitors do what?
Block the interactions between PD-L1 on tumor cells and PD-1 on T cells thereby restoring the body's ability to launch and anti-tumor immune response and kill tumor cells
NCCN Categories of Preference?
1. Preferred Intervention: based on efficacy, safety, and evidence and when appropriate, affordability
2. Other recommended Intervention: may be somewhat less efficacious, more toxic, or based on less mature data, or significantly less affordable for similar outcomes
3. Useful in Certain Circumstances: Other interventions that may be used to selected patient populations (defined with recommendation)
What are the two types of radiation therapy that may be given to patients with SCLC?
1. Thoracic radiation (most common) Standard of Care for LS-SCLC w/Chemo. In ES-SCLC it is reserved for patients who have responded to 1st line systemic therapy
2. Cranial irradiation: radiation given to brain in some patients with SCLC to reduce risk of cancer spread to brain. *more common in LS-SCLC *Associated with neurotoxicity (>60yrs)
Both Cisplatin and Carboplatin are used in SCLC when combined with?
Etoposide
Cisplatin since 1985
Carboplatin: 1999
What is the most commonly used aklylating agent?
and
What did it not do in SCLC studies?
Lurbinectedin.
Commonly used in SCLC, but failed to meet their primary endpoint. Does remains on the market under accelerated approval status.
Adverse Events In Lung Cancer for:
Atezolizumab (Tecentriq)
Durvalumab (Imfinzi)
Atezolizumab: Fatigue, Nausea, alopecia, constipation, diarrhea, decreased appetite
Durvalumab: Nausea, fatigue, alopecia
NCCN-Recommended Primary or Adjuvant Therapy regimens for Limited Stage SCLC (LS-SCLC)
Guidelines recommend 4 treatment cycles (cisplatin or carboplatin with etoposide), each 21 to 28 days in length
Systemic therapy regimens are given concurrently with radiation therapy.
*All 2A NCCN Recommendations
What is the most common type of thoracic radiation given to patients with SCLC?
EBRT: External beam radiation therapy
What are the 3 box warnings for Cisplatin?
and
What are the 2 box warnings for Carboplatin?
Cisplatin:1. Renal toxicity 2. ototoxicity (damage to the ears) 3. Anaphylactic-like reactions
Carboplatin: 1. myelosuppression 2.Anaphylactic-like reactions
Carboplatin is does in unique ways: explain.
Dosing is calculated according to two parameters:
1. how well a patients kidneys are functioning, measure in terms of the glomerular filtration rate (GFR)
2. the desired amount of carboplatin that the body is exposed to (target exposer), represented by the area under the curve (AUC)
Two Immunotherapies that are FDA-approved for multiple cancer types, but not SCLC?
Nivolumab (Opdivo) and pembrolizumab (Keytruda).
Both were FDA-approved for 3rd line treatment of SCLC at one time, through accelerated approval process. However, the SCLC indications for both agents were withdrawn n 2021, base on the failure to verify clinical benefit in confirmatory trials. Nevertheless they are both included in NCCN guidelines.
NCCN Recommended regimens for Extensive SCLC (ES-SCLC)
NCCN-Preferred regimens: All FDA approved, guidelines recommend 4 treatment cycles, although some patients may receive up to 6 cycles based on tolerability after first 4.
* all treatments involve Cisplatin or carboplatin along with etoposide and atezolizumab or Durvalumab followed by maintenance of that IO every 21 or 28 days