41.

Approved agents for

treatment of NSCLC following
relapse after 1st line
treatment
FDA approved
Docetaxel
Erlotinib
Pemetrexed (best RR
and OS)
7. Beta Carotene Increases the risk of Lung
cancer + or - retinol and or
Vit A
No proven
chemoprevention except
stop smoking
49. Carboplatin activity Similar activity of
cisplatin
Carboplatin not
interchangeable with
cisplatin in certain
diseases
50. Carboplatin Toxicity Myelosuppression
(Thrombocytopenia -
DLT)
Dosed on AUC and uses
the equation
Ototoxicity
45. Cisplatin activity Solid tumors (lung,
testicular, ovarian,
cervical, head and
neck, endometrial,
bladder, gastric,
melanoma
47. Cisplatin Elimination Renally
Hold/adjust dose if SCr
> 1.5 or Clcr < 60 ml/min
46. Cisplatin Toxicity Renal failure (DLT)
Nausea (highly
emetogenic in doses > 50
mg/m2 - DLT)
Generally not severely
myelosuppressive
48. Cisplatin Toxicity
management
Aggressive hydration
with NS + electrolyte (Mg,
K)
Baseline audiogram for
their hearing
High antiemetic regimen
(aprepitant, 5HT-3 RA,
steroid)
54. CORNERSTONE OF
TREATMENT for NSCLC
PLATINUM BASED
DOUBLET
Several equally effective
regimens from which to
choose based on patient
14. diagnosing and
staging
Physical exam
Pulmonary function test to evaluate for
surgical eligibility
H&P, CBC, CMP
NSCLC: Mediastinoscopy, abdominal
CT (Surgical planning)
+/- brain MRI (only if in the brain)
Molecular and genetic studies (EGFR,
k-ras, and so on)
53. DLT of platin
drugs
60. ED-SCLC
treatment
Palliative
Treatment: CE (carboplatin +
etoposide)
42. Erlotinib blocks activity by inhibiting intracellular
tyrosine kinase
Treatment of locally advanced or
metastatic NSCLC that
has failed to respond to at least 1 prior
regimen
13. Evaluation and
staging
Primary tumor evaluation uses CXR
and/or Chest CT
Tissue: Sputum cytology,
Bronchoscopy, Transthoracic needle bx,
Thoracentesis
Location by Histology
Adenocarcinoma and large cell is
periphery
Squamous and small cell is central in
origin
24. Extensive SCLC
progression
Palliation (want to control the dx)
1st line chemotherapy regimen
Platinum-based chemotherapy doublet-
2 drug regimen
Carboplatin can be substituted for
cisplatin for ED-SCLC
Given every 3-4 weeks, Repeated x 4-6
cycles
25. Extensive SCLC
progression
prophylactic
cranial
irradiation
Recommended only if patient achieves a
good response to chemotherapy
39. Flex Trial Overall survival with addition of
cetuximab to cisplatin + vinorelbine (11.3
v. 10.1 mos)
increased life by one month
Lung cancer
Study online at quizlet.com/_3cm9j
10. I-ELCAP
(international early
stage lung cancer
action program)
Annual CT... CT scan can
increase detection of early stage
lung cancer (stage I) and increase
survival if treated
Most patients with initial dx of lung
cancer are found to be tumor loaded
and leads to poor prognosis
1. Mortality rates Number 1 cause of cancer-related
death in both men and women
5. Most modifiable risk
factor
Smoking
Accounts for ~ 90% of SCLC cases
KY has the highest smoking rate in
the U.S.
9. NCI NLST (national
lung screening trial)
Early results released November
2010
20% reduction in risk of dying
from cancer in patients screened
with low-dose (helical) CT scan....
(CT scan)
This may be recommended by some
physicians but very expensive
36. Non-resectable
Advanced metastatic
NSCLC drugs used
Platinum-based doublet regimens
used inNSCLC
Cisplatin PLUS any of the
following
Paclitaxel
Docetaxel
Gemcitabine
Pemetrexed
Etoposide
Vinorelbine
All of these are equivalent and can
be interchanged in Pt conditions
Carboplatin PLUS Paclitaxel
35. Non-resectable
Advanced metastatic
stage 4 NSCLC
Initiation of Chemo then
maintenance
1st line therapy = Chemotherapy
Platinum-based doublet regimen
Administration of 4 - 6 cycles
Maintenance Therapy for Pts with
good response
Prolongation of anti-cancer
therapy after completion
of 4 - 6 cycles of adjuvant
chemotherapy in the absence of
disease progression
38. NSCLC
maintenance
Premextred
Indicated in locally advanced or metastatic
NSCLC that has not
progressed after 4 cycles of platinum based
chemotherapy
Do not use in Squamous Cell No activity
Concurrent medications
Folic acid, Vitamin B12 prevent severe
myelotox
37. NSCLC
maintenance
therapy
Continued use of one of the agents
utilized in 1st
line therapy after completion of 4 -6 cycles
Agents: pemetrexed, cetuximab,
bevacizumab only approved
Switch Maintenance
Initiation of a new agent not utilized in
1st line therapy after completion of 4 - 6
cycles
Agents: pemetrexed, erlotinib, docetaxel
Only FDA approved
Maintenance therapy is continued until
patient progresses or has intolerable
toxicity
11. NSCLC
presentation
Cough
Blood in sputum
chest pain
hoarseness
B symptoms
S. Vena Cava syndrome
Bone Pain due to metastasis
LFTs/LDH
Horner's Syndrome eyelid droops
Pancoast's syndrome 8th cranial nerve
with arm pain
Mental status changes
Anorexia-cachexia syn have no desire to
smoke and dont want to eat
Night sweats (most common
Shoulder pain
Hypertrophic pulmonary osteoarthropathy
pain in the joints
Neurologic paraneoplasia
Hypercalcemia
40. NSCLC
recurrent Tx
Second-line chemotherapy for locally-
advanced
and metastatic NSCLC
No evidence confirming/refuting
improvement in survival
51. Oxaliplatin
Activity
Colorectal cancer and pancreatic cancer
52. Oxaliplatin Toxicity Peripheral neuropathy - DLT
Extreme Cold intolerance
Laryngeal spasms and feel like they
cant breathe
62. Pack year history How long the patient has been
smoking and risk exposure is.
1 pack a day for 20yrs = 20yr pack
history
2 packs a day for 20 yrs = 40yr pack
history
1/2 a pack a day for 20 yrs = 10yr pack
history
Relates to risk of cancer
3. Pathology NSCLC Adenocarcinoma
Most common in nonsmokers
Tumors commonly identified as
peripheralnodules
Squamous cell
Slower growing - better prognosis
Clear relationship with smoking
Tumors located centrally &
peripherally
Large cell carcinoma
2. Pathology SCLC Characterized by rapid growth and
early metastases
Clear relationship to smoking
31. Pathology types of
NSCLC
Adenocarcinoma (40%)
Most common in non-smokers
Tumors commonly identified as
peripheral nodules
Hematogeneous dissemination
recurring outside of the
thorax
Squamous cell (30%)
Slower growing - better prognosis
Clear relationship with smoking
Tumors located centrally &
peripherally
Recurs locally after treatment
Large cell carcinoma (15%)
23. PCI (prophylactic
cranial irradiation)
SCLC
Recommended after achieving a CR
(complete remission) to prevent brain
metastases
10 doses over 2 weeks
44. Platinum agents MOA Attaches to the DNA strand on guanine
and adenine residues and gets stuck in
the DNA in G and A forming an adduct
Monoadducts further react to form
crosslinks two
separate ways
Intrastrand: crosslinks between
guanines located on the
same strand
Interstrand: crosslinks between
guanines located on
opposite strands
This blocks 3D form of DNA
Damaged cells undergo apoptosis
43. Platnum drugs
structure
Larger better for a DNA road block
58. Recurrence/2nd line
regimens NSCLC
Docetaxel, erlotinib, pemetrexed,
investigational agents
61. Recurrence/Refractory
SCLC
Topotecan is the drug of choice for
26. Recurrent SCLC Progressive disease requires immediate
palliation (patient is often symptomatic)
29. Recurrent Tx options Single agents with activity in 2nd line
therapy
Topotecan (only one approved for 2nd
line recurrent)
Irinotecan
Gemcitabine
Paclitaxel
Docetaxel
Vinorelbine
28. Refractory disease
SCLC
Progresses < 90 days after 1st line
therapy
Chemotherapy resistant (< 10% RR)
27. Relapse disease SCLC Progresses > 90 days after 1st line
therapy
Chemotherapy sensitive (20 - 30% RR)
has a better prognosis when treated with
chemo
33. Resectable non-
metastatic NSCLC
Early Stage (I, II)
Gold standard of care = Surgery +
Adjuvant Chemotherapy
All patients considered surgical
candidates
Adjuvant chemotherapy
Platinum-based doublet chemo for
stages Ib, II
Dont use radiation
34. Resectable non-
metastatic NSCLC
Early Stage III
Neoadjuvant chemotherapy +/-
Radiation followed by Surgery
Neoadjuvant chemotherapy =
Cisplatin-based doublet regimen
6. Risk factors Radon / Ionizing radiation is 2nd
biggest risk factor
Asbestos
Work related exposure
Underlying lung disease
Pulmonary fibrosis Emphysema
Coal worker
Increasing age
Being male
16. SCLC characteristics Aggressive form of lung cancer
(very fast)
Highly sensitive to chemotherapy
and RT
Most patients have extensive
disease at presentation
Surgery indicated only for very
early disease
Overall survival is very, very, very
POOR
smaller percent have this
Only two stages Limited and
Extensive
18. SCLC Extensive stage
disease
If cant radiate in a single field
(60-70%)
distant metastases or any disease at
a site beyond
the definition of limited disease
59. SCLC LD-SCLC
treatment
Early stage is the time surgical
intervention is appropriate
Combined modality treatment:
Concurrent radiation with
PE (cisplatin + etoposide) and PCI
17. SCLC Limited stage
disease
If can radiate in a single field
(30-40%)
tumor confined to one hemithorax
and regional lymph nodes
(mediastinum or supraventricular)
lesion(s) must be able to be
encompassed within a tolerable
radiation therapy port
19. SCLC Mortality w/o tx Limited stage disease < 12 weeks
Extensive stage disease = 5-7
weeks
20. SCLC Mortality with
Tx (Tx at best
response 20%
survival)
Limited disease = 16-20 months
Extensive disease = 9-11 months
Cancer can have a good response
but cancer returns and grows back
very quickly
Limited survival with good Tx
response
12. SCLC
presentation
Cough 100% of the time
Blood in sputum
chest pain
hoarseness
B symptoms
S. Vena Cava syndrome
Bone Pain due to metastasis
Mental status changes (10%)
Hypertrophic pulmonary
osteoarthropathy
SIADH
Cushing's
Neurologic paraneoplasia which is very
odd to deal with (Eaton-Lambert
syndrome)
ACTH syndrome
Hypercalcemia
30. SCLC Tx factors Maintaining dose intensity does not
improve patient outcome
Colony Stimulating Factors are not
cost effective
and do not improve patient outcome,
thus should be avoided in lung cancer
Elderly or debilitated have a very poor
prognosis
- Consider less toxic regimens and
palliation is the goal
21. SCLC Tx options Surgery not standard of care but done
if limited to single loci
Chemotherapy
Radiation
SCLC is very sensitive to chemotherapy
and radiation but upon presentation it
tends to be all over the body
22. SCLC Tx options
Limited stage
Surgery Only for patients with a
solitary lung nodule Usually combined
with chemotherapy
Concurrent chemotherapy and XRT
Always CISPLATIN containing
regimen 4 cycles
Chemotherapy: PE = Cisplatin +
Etoposide (4 cycles total)
PLUS
Thoracic radiation
Begin on day one of the 1st cycle of
chemotherapy (3 weeks)
8. Screening
recommendations
by the NCI and
ACS
Insufficient evidence to determine if
screening reduces mortality
Harm of false positive over-diagnosis
leading to unnecessary surgeries and
anxiety
Do not recommend even in high-risk
15. Sites of metastasis Liver
Lymph nodes
Bone
High rate of spinal cord compression
Bone marrow
Brain is a target for the SCLCs
Adrenal glands (NSCLC)
55. Stage I & II treatment NSCLC Surgical resection = best option for cure
With cisplatin-based doublet for stage Ib, II
56. Stage III treatment for NSCLC Neoadjuvant chemoradiation with surgery
4. Tobacco 80% of Lung cancer occurs in smokers
85% lung cancer deaths attributed to smoking
32. Treatment for NSCLC Surgery (lobectomy, pneumonectomy)
Radiation
Chemotherapy Standard of care- Platinum-based doublet chemotherapy
Treatment is determined by stage & Performance Status
57. Unresectable and Stage IV treatment
NSCLC
Resect limited metastatic sites (brain, adrenal), platinum-based chemotherapy regimen,
palliative radiation
Consider maintenance therapy in patients without progression on platinum-based initial
therapy