Fine needle biopsy - thin needle passed between ribs into mass in the lung with the aid of fluoroscope

Bronchoscopy - Lighted, flexi tube passed through mouth into bronchi, checks lung lining

Mediastinoscopy - General anesthesia used while lighted tube passed through cut in base of neck under breastbone --> checks lymph nodes

Thoracentesis - Needle placed between ribs to drain fluid around lungs to see if cancer in pleural membrane or due to another cause

Thoracoscopy - Thin, lighted tube with camera to view space between lungs and chest wall --> looks for  tumors on surface of lungs

NSCLC (non-small cell lung cancer --> most common, typically better prognosis, TNM stages 0-IV

SCLC --> Less common, worse prognosis, limited stage and extensive stage

Mesothelioma --> Least common, cancer in pleura of lungs, not IN lungs.  Surgery is needed; Pemetrexed plus cisplatin in non-resectable, result of asbestos exposure

- YES!

- This is NOT lung cancer

- Treat according to primary cancer

- Some cancers that metastasize to the lungs: breast, pancreas, kidney, skin

- First and foremost, smoking!

- Second-hand smoke

- Arsenic

- Benzene

- Radon

- Asbestos (mesothelioma)

- Radiation exposure

- Air pollution

- TB

- Family history

- Age > 65

- persistent cough

- hemoptosis

- chest pain

- recurring pneumonia or bronchitis

- weight loss and loss of appetite

- SOB

- Fever of unknown origin

- Headaches, change in vision or speech

I - Cancer confined to lung and not more than 3cm in diameter

II - Cancer is either: >3cm, OR invades nearby lymph nodes, OR invades other parts of pulmonary system but without lymph nodes

III - Cancer spread to more distant lymph nodes or to other organs

IV - Multiple spots in same lung OR cancer in both lungs OR distant metastases

Limited stage - Cancer in 1 lung and lymph nodes on same side of chest.

Extensive stage - Cancer spread to second lung or to lymph nodes on other side of chest or to pleural space.

- Earlier than in other diseases

- Neoadjuvant: w/ XRT for large but operable Stage III

- Adjuvant: Alone or w/ XRT depending on the setting

- Metastatic disease --> alone for palliation

- Survival predicted by baseline stage, weight loss, performance status, gender

In good PS patients, platinum-based chemo improves:

- PFS by 4-6 months

- Median survival by 8-10 months

- 1-year survival by 30-40%

- 2-year survival by 10-15%

In regards to chemo:

- Does not help ECOG PS 3 or 4, regardless of age

- Platinum-based therapies preferred

- 2 drugs better than 3 except --> when third drug is Cetuximab/Bevacizumab and patient is treatment naive (ECOG PS 0 or 1)

- 4 cycles of cisplatin-based chemo is best --> Vinorelbine or Vinblastine or Etoposide

- If patient can't take cisplatin --> 4 cycles of carboplatin-paclitaxel

- Cisplatin + gemcitabine/docetaxel also acceptable

- Chemo-XRT:  Same drugs but with different doses/schedules to be used with XRT --> Cisplatin, Etoposide, Vinblastine, Carbo-taxol

First:  Platinum-based (cis or carbo) +/- bevacizumab

Second: Pemetrexed, docetaxel, erlotinib preferred.  Other platinum combos --> Vincas, gemcitabine, etoposide, irinotecan, docetaxel OK

Third:  Erlotinib preferred, anything not used second line

- Not for squamous cell histology --> clinically significant hemoptosis

- PS 0 or 1, treatment naive

- Not for brain mets

- Not if h/o hemoptosis

- Not if on anti-coagulation or if clotting disorder

       First line:  

Carboplatin: 

- Less N/V, but requires 5HT3 drug

- Less renal dysfunction

- More myelosuppression

- Dose based on AUC (in lung it's 5-7)

- Use CG to calculate CrCl

- Dose = (CrCl + 25)(target AUC)

Cisplatin:

- Reference drug for N/V

- Doses > 70mg/m2 need aprepitant

- More renal, less Myelo

- In adjunvant therapy, MORE effective than Carbo in NSCLC

- Both equally effective in metastatic disease

Paclitaxel:

- Different doses used

- Not water soluble

- Cremophor solvent causes infusion rxns

- Peripheral neuropathy

- Myelosuppression

Docetaxel:

- Not really associated with infusion rxns

- Edema, need Dexa 8mg BID before, day of, and after chemo

- Neutropenia

Adverse events shared by both:

- Mucositis

- Alopecia

- Adjust for bili, no renal adjustments

- Both 3A4 substrate

- NEVER PUT VINES IN THE SPINE!!!

- IV push or short infusion

- Alopecia, n/v, peripheral neuropathy, constipation, diarrhea (mild) are all adverse events

- P450 3A4 substrate

Vincristine:

- Dose-limiting neurotoxicity

- Constipation that can turn into paralytic ileus

- Orthostatic HTN

- Not myelosuppressive

- SIADH

- Adjust for bili

- No renal adjustments

Vinblastine: 

- Dose-limiting myelosuppression

- Rare muscle aches

- Constipation or diarrhea

- Adjust for bili

- No renal adjustments

-  Topoisomerase I inhibitor

- Various dosing schedules

- Acute or delayed diarrhea --> Use atropine for first 24 hours, loperamide > 24 hours

- Alopecia, N/V, myelosuppression, hepatic dysfunction, no renal adjustments, hold for bili > 2

- Mitotic inhibitor

- 50% bioavailable (PO needs 2x the dose of IV)

- Dose-limiting myelosuppression

- Alopecia, N/V, anorexia with PO, high dose-limiting mucositis, asthenia/malaise, secondary leukemias, SJS, epidermal necrolysis

- Orthostatic HTN

- Adjusted for renal and hepatic dysfunction

- Single agent, 2nd line for NSCLC

- With cisplatin, 1st line for non-resectable mesothelioma

Supportive Care:

- Need 1000mg folic acid qd 1-2 weeks prior

- Vitamin B12 1000mcg IM 1-2 weeks prior q 3 cycles

- Dexamethasone 4mg po BID day before, of, and after chemo to prevent rash

-  Rash, myelosuppression, fever/infection, stomatitis/pharyngitis

- Hold for CrCl <45 of Bili > 2

- Targed therapy

- Small molecular weight EGFR-TKI inhibitor

- Class effects include rash/diarrhea

- Other meds in this class include Erlotinib (Tarceva) and Bevacizumab (Avastin; targets VEGF)

Study summary:

Oral EGFR-TKI approved in May 2003 as 3rd line for NSCLC based on 10% RR…..

IMPACT 1 and IMPACT 2 demonstrated no survival advantage over standard chemotherapy

June 2005: FDA changes indication:

“…monotherapy for the continued treatment of patients with [NSCLC]…who are benefiting or have benefited from IRESSA”

But being investigated in other diseases

- Tyrosine kinase inhibitor of EGFR

- NSCLC: 150mg po daily, 100mg if pancreatic cancer

- Dose-limiting diarrhea and acneiform rash

- Rash may correlate with response

- 3A4 sub, could affect INR

- Smoking increases clearance by 24%

- No renal/hepatic adjustments