Lung cancer

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41.

Approved agents for treatment of NSCLC following relapse after 1st line treatment Beta Carotene

FDA approved Docetaxel Erlotinib Pemetrexed (best RR and OS) Increases the risk of Lung cancer + or - retinol and or Vit A No proven chemoprevention except stop smoking Similar activity of cisplatin Carboplatin not interchangeable with cisplatin in certain diseases

14.

diagnosing and staging

7.

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

49.

Carboplatin activity

60.

ED-SCLC treatment Erlotinib

50.

Carboplatin Toxicity

Myelosuppression (Thrombocytopenia DLT) Dosed on AUC and uses the equation Ototoxicity Solid tumors (lung, testicular, ovarian, cervical, head and neck, endometrial, bladder, gastric, melanoma Renally Hold/adjust dose if SCr > 1.5 or Clcr < 60 ml/min Renal failure (DLT) Nausea (highly emetogenic in doses > 50 mg/m2 - DLT) Generally not severely myelosuppressive

Palliative Treatment: CE (carboplatin + etoposide) 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

42.

45.

Cisplatin activity

13.

Evaluation and staging

47.

Cisplatin Elimination

46.

Cisplatin Toxicity

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 Palliation (want to control the dx) 1st line chemotherapy regimen Platinum-based chemotherapy doublet2 drug regimen Carboplatin can be substituted for cisplatin for ED-SCLC Given every 3-4 weeks, Repeated x 4-6 cycles Recommended only if patient achieves a good response to chemotherapy

24.

Extensive SCLC progression

48.

Cisplatin Toxicity management

Aggressive hydration with NS + electrolyte (Mg, K) Baseline audiogram for their hearing High antiemetic regimen (aprepitant, 5HT-3 RA, steroid) PLATINUM BASED DOUBLET Several equally effective regimens from which to choose based on patient

25.

54.

CORNERSTONE OF TREATMENT for NSCLC

Extensive SCLC progression prophylactic cranial irradiation Flex Trial

39.

Overall survival with addition of cetuximab to cisplatin + vinorelbine (11.3 v. 10.1 mos) increased life by one month

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

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

1.

Mortality rates Most modifiable risk factor

Number 1 cause of cancer-related death in both men and women Smoking Accounts for ~ 90% of SCLC cases KY has the highest smoking rate in the U.S. 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
37.

5.

NSCLC maintenance therapy

9.

NCI NLST (national lung screening trial)

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

36.

Non-resectable Advanced metastatic NSCLC drugs used

Platinum-based doublet regimens used inNSCLC

11.

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.

NSCLC presentation

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
40.

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 Second-line chemotherapy for locallyadvanced and metastatic NSCLC No evidence confirming/refuting improvement in survival

NSCLC recurrent Tx

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

44.

Platinum agents MOA

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 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
43.

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

3.

Pathology NSCLC

Platnum drugs structure

Larger better for a DNA road block

58.

Recurrence/2nd line regimens NSCLC Recurrence/Refractory SCLC Recurrent SCLC Recurrent Tx options

Docetaxel, erlotinib, pemetrexed, investigational agents Topotecan is the drug of choice for Progressive disease requires immediate palliation (patient is often symptomatic) Single agents with activity in 2nd line therapy Topotecan (only one approved for 2nd line recurrent) Irinotecan Gemcitabine Paclitaxel Docetaxel Vinorelbine Progresses < 90 days after 1st line therapy Chemotherapy resistant (< 10% RR) Progresses > 90 days after 1st line therapy Chemotherapy sensitive (20 - 30% RR) has a better prognosis when treated with chemo 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

61.

2.

Pathology SCLC

Characterized by rapid growth and early metastases Clear relationship to smoking 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%) Recommended after achieving a CR (complete remission) to prevent brain metastases 10 doses over 2 weeks

26.

31.

Pathology types of NSCLC

29.

28.

Refractory disease SCLC Relapse disease SCLC

27.

23.

PCI (prophylactic cranial irradiation) SCLC

33.

Resectable nonmetastatic NSCLC Early Stage (I, II)

34.

Resectable nonmetastatic NSCLC Early Stage III Risk factors

Neoadjuvant chemotherapy +/Radiation followed by Surgery Neoadjuvant chemotherapy = Cisplatin-based doublet regimen Radon / Ionizing radiation is 2nd biggest risk factor Asbestos Work related exposure Underlying lung disease Pulmonary fibrosis Emphysema Coal worker Increasing age Being male 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 If cant radiate in a single field (60-70%) distant metastases or any disease at a site beyond the definition of limited disease Early stage is the time surgical intervention is appropriate Combined modality treatment: Concurrent radiation with PE (cisplatin + etoposide) and PCI

12.

SCLC presentation

6.

16.

SCLC characteristics

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 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

30.

SCLC Tx factors

18.

SCLC Extensive stage disease

21.

SCLC Tx options

59.

SCLC LD-SCLC treatment

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 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)

22. 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 Limited stage disease < 12 weeks Extensive stage disease = 5-7 weeks 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
8.

SCLC Tx options Limited stage

19.

SCLC Mortality w/o tx

20.

SCLC Mortality with Tx (Tx at best response 20% survival)

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) Surgical resection = best option for cure With cisplatin-based doublet for stage Ib, II Neoadjuvant chemoradiation with surgery 80% of Lung cancer occurs in smokers 85% lung cancer deaths attributed to smoking Surgery (lobectomy, pneumonectomy) Radiation Chemotherapy Standard of care- Platinum-based doublet chemotherapy Treatment is determined by stage & Performance Status

55.

Stage I & II treatment NSCLC Stage III treatment for NSCLC Tobacco Treatment for NSCLC

56. 4.

32.

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