Cancer Association of South Africa (CANSA)

Transcription

1 Cancer Assciatin f Suth Africa (CANSA) Fact Sheet n Lung Cancer Intrductin The chest cntains tw lungs, ne lung n the right side f the chest, the ther n the left side f the chest. Each lung is made up f sectins called lbes the right lung cnsists f three lbes and the left lung cnsists f tw lbes. The lung is sft and prtected by the ribcage. The purpses f the lungs are t absrb xygen (O2), int the bldstream fr distributin thrughut the bdy and t remve carbn dixide (CO2), a waste prduct, frm the bdy. [Picture Credit Anatmy f the Lungs] Lung Cancer Lung cancer is a disease characterised by uncntrlled cell grwth in tissues f the lung. If left untreated, this grwth can spread beynd the lung in a prcess called metastasis int nearby tissue and, eventually, int ther parts f the bdy. Mst cancers that start in lung, knwn as primary lung cancers, are carcinmas that derive frm epithelial cells. Incidence f Lung Cancer in Suth Africa Accrding t the Natinal Cancer Registry (2012) the fllwing number f lung cancer cases was histlgically diagnsed in Suth Africa during 2012: Researched and Authred by Prf Michael C Herbst [D Litt et Phil (Health Studies); D N Ed; M Art et Scien; B A Cur; Dip Occupatinal Health] Apprved by Ms Elize Jubert, Chief Executive Officer [BA Scial Wrk (cum laude); MA Scial Wrk] May 2017 Page 1

2 Grup - Males 2012 Actual N f Cases Estimated Lifetime Risk Percentage f All Cancers All males :79 4,72% Asian males 85 1:57 10,14% Black males 691 1:131 5,92% Clured males 355 1:34 8,19% White males :53 3,05% Grup - Females 2012 Actual N f Cases Estimated Lifetime Risk Percentage f All Cancers All females 814 1:232 2,16% Asian females 23 1:257 2,16% Black females 234 1:558 1,42% Clured females 169 1:96 4,06% White females 387 1:98 2,44% The frequency f histlgically diagnsed cases f lung cancer in Suth Africa fr 2012 was as fllws (Natinal Cancer Registry, 2012): Grup - Males All males Asian males Black males Clured males White males Grup - Females All females Asian females Black females Clured females White females N.B. In the event that the ttals in any f the abve tables d nt tally, this may be the result f uncertainties as t the age, race r sex f the individual. The ttals fr all males and all females, hwever, always reflect the crrect ttals. Types f Lung Cancer There are tw main types f lung cancer, nn-small cell lung cancer and small cell lung cancer. These names refer t hw the cancers lk under a micrscpe t a pathlgist. Mst lung cancers are nn-small cell. There are subtypes f nn-small cell lung cancer. Because different types f lung cancer are treated differently, an nclgist will determine exactly what treatment is best. Nn-Small Cell Lung Cancer (NSCLC) NSCLC accunts fr abut 80% f lung cancers. There are different types f NSCLC, including: Researched and Authred by Prf Michael C Herbst [D Litt et Phil (Health Studies); D N Ed; M Art et Scien; B A Cur; Dip Occupatinal Health] Apprved by Ms Elize Jubert, Chief Executive Officer [BA Scial Wrk (cum laude); MA Scial Wrk] May 2017 Page 2

3 Squamus cell carcinma (als called epidermid carcinma) - this is the mst cmmn type f NSCLC. It frms in the lining f the brnchial tubes and is the mst cmmn type f lung cancer in men. Adencarcinma - this cancer is fund in the glands f the lungs that prduce mucus. This is the mst cmmn type f lung cancer in wmen and als amng peple wh have nt smked. Brnchi-alvelar carcinma - this is a rare subset f adencarcinma. It frms near the lungs' air sacs. Recent clinical research has shwn that this type f cancer respnds mre effectively t the newer targeted therapies. Large-cell undifferentiated carcinma - this cancer frms near the surface, r uter edges, f the lungs. It can grw rapidly. Small Cell Lung Cancer (SCLC) SCLC accunts fr abut 20% f all lung cancers. Althugh the cells are small, they multiply quickly and frm large tumurs that can spread thrughut the bdy. Smking is almst always the cause f SCLC. There are tw types f SCLC. The cancer cells f each type grw and spread in different ways. The types f small cell lung cancer are named fr the kinds f cells fund in the cancer and hw the cells lk when viewed under a micrscpe: Small cell carcinma (at cell cancer) Cmbined small cell carcinma (LungCancer.Org; May Clinic; Natinal Cancer Institute). Causes f Lung Cancer Lung cancer has always been and still is mre cmmn in men. As mre wmen have started smking, the number f wmen develping lung cancer has been n the increase. Peple wh d nt smke can als develp lung cancer. Apprximately 10 15% f peple wh get lung cancer have never smked. Other risk factrs include the effects f past cancer treatment and expsure t asbests, radn gas and in very rare cases substances such as uranium, chrmium and nickel. Lung cancer is nt infectius and can t be passed n t ther peple. Smking - The mre ne smkes, the greater the risk f develping lung cancer. It is als mre likely t develp in peple wh start smking at a yung age. If smene stps smking, their risk f develping lung cancer falls quite quickly. After abut 15 years, the chance f develping the disease is similar t that f a nn-smker. This sectin n smking includes the use f: Hkah e-hkah In the event f smene quitting t smke, psitive health benefits can immediately be experienced. The fllwing indicates the health benefits that can be expected upn quitting the habit f smking: Researched and Authred by Prf Michael C Herbst [D Litt et Phil (Health Studies); D N Ed; M Art et Scien; B A Cur; Dip Occupatinal Health] Apprved by Ms Elize Jubert, Chief Executive Officer [BA Scial Wrk (cum laude); MA Scial Wrk] May 2017 Page 3

4 Within: 20 minutes - the bld pressure, pulse rate and the temperature f ne s hands and feet have returned t nrmal 8 hurs the remaining nictine in ne s bldstream will have fallen t 6.25% f nrmal peak daily levels, a 93.75% reductin 12 hurs - bld xygen level will have increased t nrmal and carbn mnxide levels will have drpped t nrmal 72 hurs One s entire bdy will test 100% nictine-free and ver 90% f all nictine metablites (the chemicals it breaks dwn int) will nw have passed frm the bdy via ne s urine. Symptms f chemical withdrawal have peaked in intensity, including restlessness. The number f cue induced crave episdes experienced during any quitting day will peak fr the average ex-user. Lung brnchial tubes leading t air sacs (alveli) are beginning t relax in recvering smkers. Breathing is becming easier and the lung's functinal abilities are starting t increase 5-8 days - the average ex-smker will encunter an average f three cue induced crave episdes per day. Althugh we may nt be average and althugh serius cessatin time distrtin can make minutes feel like hurs, it is unlikely that any single episde will last lnger than 3 minutes. Keep a clck handy and time them. 2 t 4 weeks - cessatin related anger, anxiety, difficulty cncentrating, impatience, insmnia, restlessness and depressin have ended. If still experiencing any f these symptms get seen and evaluated by yur physician 8 weeks - insulin resistance has nrmalised despite average weight gain f 2.7 kg (1997 study). 1 year - the excess risk f crnary heart disease, heart attack and strke have drpped t less than half that f a smker 5 years - the risk f a subarachnid haemrrhage has declined t 59% f previus risk while still smking (2012 study). In a female ex-smker, the risk f develping diabetes is nw that f a nn-smker (2001 study) 5 t 15 years - the risk f strke has declined t that f a nn-smker 10 years - the risk f being diagnsed with lung cancer is between 30% and 50% f that fr a cntinuing smker (2005 study). Risk f death frm lung cancer has declined by almst half fr an average smker (ne pack per day). Risk f cancer f the muth, thrat, esphagus and pancreas have als declined. Risk f develping diabetes fr bth men and wmen is nw similar t that f smene wh never smked (2001 study) 15 years - the risk f crnary heart disease is nw that f a persn wh has never smked. The risk f pancreatic cancer has declined t that f smene wh never smked (2011 study (WhyQuit). In a recent study by Alexandrv, et al., (2016) their analysis shws a direct link between the number f cigarettes smked in a lifetime and the number f mutatins in tumur DNA. The researchers fund that, n average, smking a packet f cigarettes a day led t: 150 mutatins in each lung cell every year 97 in the larynx r vice bx 23 in the muth 18 in the bladder six in the liver Researched and Authred by Prf Michael C Herbst [D Litt et Phil (Health Studies); D N Ed; M Art et Scien; B A Cur; Dip Occupatinal Health] Apprved by Ms Elize Jubert, Chief Executive Officer [BA Scial Wrk (cum laude); MA Scial Wrk] May 2017 Page 4

5 Accrding t the researchers, the mre mutatins there are, the higher the chance that these will ccur in the key genes that are called cancer genes, which cnvert a nrmal cell int a cancer cell. Passive smking- breathing in ther peple s cigarette smke (passive smking) increases the risk f lung disease and cancer Pipes and cigars - althugh pipe and cigar smkers have a lwer risk f lung cancer than cigarette smkers, they are still at a much greater risk fr lung cancer than nn-smkers with an increased risk f cancer f the lip Cannabis - Cannabis smke cntains a similar prfile f carcingenic (cancer causing) chemicals as tbacc smke and is inhaled mre deeply. Althugh cannabis smke is knwn t cntain similar harmful and carcingenic substances t tbacc smke, relatively little is still currently understd regarding the respiratry health effects frm cannabis smking (Gates, et al.). Radiatin therapy t the Chest - cancer survivrs wh had radiatin therapy t the chest are at higher risk f lung cancer. Patients at highest risk include thse treated fr Hdgkin disease and wmen with breast cancer treated with radiatin after a mastectmy (but nt a lumpectmy) Radn gas radn is a clurless, durless radiactive gas that frms frm the decay f radiactive elements such as uranium. The radn gas given ff by sil and rck can enter hmes and buildings thrugh cracks in flrs and walls, pipe, wires and pumps. Radn cncentratins are usually highest in basements r in undergrund mining envirnments. It can als be released frm undergrund water supplies in small amunts. Expsure can als ccur frm building materials made frm radn cntaining substances. Expsure t high cncentratins f radn can increase the risk fr develping lung cancer. It is believed that apprximately 9% f lung cancers may be caused by expsure t radn. Smking, radn, and secndhand smke are the leading causes f lung cancer. Radn is the number ne cause f lung cancer amng nn-smkers, accrding t Envirnmental Prtectin Agency (EPA) estimates. Overall, radn is the secnd leading cause f lung cancer Age - like mst types f cancer, lung cancer is mre cmmn in lder peple. Abut 80% f lung cancers are diagnsed in peple ver 60. Lung cancer rarely affects peple under 40 Genetic risk - sme peple with a clse relative wh has had lung cancer may be at an increased risk f it themselves, althugh the increase in risk is very small. The risk is slightly greater if a relative is a nn-smker and develped lung cancer at an early age, r if mre than ne relative n the same side f the family develped lung cancer If cncerned abut a family histry f lung cancer, it helpful t read ur mre detailed infrmatin abut genetic risk r talk t a medical practitiner r health prfessinal Asbests - peple wh have been in prlnged r clse cntact with asbests have a higher risk f develping lung cancer, especially smkers. Asbests and tbacc smke act tgether t increase the risk. Many peple have been in cntact with asbests during their wrking lives. Lw-level expsure increases the risk f lung cancer nly slightly (cmpared t the risk frm smking), while heavy expsure may result in a much higher risk. Researched and Authred by Prf Michael C Herbst [D Litt et Phil (Health Studies); D N Ed; M Art et Scien; B A Cur; Dip Occupatinal Health] Apprved by Ms Elize Jubert, Chief Executive Officer [BA Scial Wrk (cum laude); MA Scial Wrk] May 2017 Page 5

6 If a persn has wrked with asbests and develp lung cancer, he/she may be able t claim cmpensatin r be paid Industrial Injuries Disablement Benefit. Mre advice can be btained frm a treating dctr, a cancer supprt rganisatins r by calling ur cancer supprt specialists. Asbests expsure als increases the risk f mesthelima, a cancer f the membranes which cver the lungs. Industrial expsure - several industrial carcingens, fr example, arsenic and plycyclic hydrcarbns as well as sme ccupatins including nn-ferrus metal prductin and painting, have been linked t lung cancer Expsure t Diesel Exhaust Fumes - diesel exhaust was classified as a cause f lung cancer by the Internatinal Agency fr Research n Cancer (IARC) in June 2012, fllwing a review f evidence mainly frm highly-expsed wrkers. IARC cited a study f diesel exhaust expsure in miners, which shwed risk f lung cancer was increased apprximately three times in thse mst heavily expsed Expsure t herbicides and insecticides - the large American Prspective Agricultural Health Study Expsure suggests that expsure t herbicides and insecticides increases lung cancer risk Occupatinal expsure t silica - silica expsure can result in silicsis with an increased risk fr lung cancer, but withut silicsis there is n increased risk. The bdy f evidence supprts an increased risk f lung cancer with expsure t asbests in nn-smkers and that risks are especially high in thse wh smke, wh als have past expsure t asbests Family Histry - a family histry f lung cancer in a first-degree relative is assciated with a tw-fld (duble) increased risk, independent f smking. If bth cancers are diagnsed befre the age f 60, the risk rati is almst five-fld. The assciatin between family histry and risk may be strnger in black individuals than white Past cancer treatment - peple wh have been treated fr sme types f cancer may have a slightly increased risk f develping lung cancer many years later. Wmen wh were treated with raditherapy fr breast cancer and wh smke may have an increased risk f lung cancer. Peple wh have been treated fr sme types f lymphma using raditherapy t the chest area as well as men wh have been treated fr testicular cancer using raditherapy t the chest area, have a slightly increased risk f lung cancer, especially if they smke. Hwever, the risk f develping lung cancer is far utweighed by the benefits f the initial treatment Diet - scientists are studying many different fds and dietary supplements t see whether they increase the risk f getting lung cancer. It is knwn that smkers wh take betacartene supplements have increased risk f lung cancer. Beta-cartene is an antixidant. It prtects the bdy frm damaging mlecules called free radicals. Free radicals damage cells thrugh a prcess knwn as xidatin. Over time, this damage can lead t a number f chrnic illnesses. There is gd evidence that eating mre antixidants fds helps bst yur immune system, prtect against free radicals, and may lwer yur risk f heart disease and cancer. But the issue is a little mre cmplicated when it cmes t taking antixidant supplements. Researched and Authred by Prf Michael C Herbst [D Litt et Phil (Health Studies); D N Ed; M Art et Scien; B A Cur; Dip Occupatinal Health] Apprved by Ms Elize Jubert, Chief Executive Officer [BA Scial Wrk (cum laude); MA Scial Wrk] May 2017 Page 6

7 Studies that lk at big grups f peple suggest that thse wh eat 4 r mre daily servings f fruits and vegetables rich in beta-cartene may reduce their risk f develping heart disease r cancer. Fds rich in beta-cartene include thse that are range r yellw, such as peppers, squashes, and carrts. A few studies have fund that peple wh take beta-cartene supplements may have a higher risk fr cnditins such as cancer and heart disease. Researchers think that may be because the ttal f all the nutrients yu eat in a healthy, balanced diet gives mre prtectin than just beta-cartene supplements alne. There is als sme evidence that when smkers and peple wh are expsed t asbests take beta-cartene supplements, their risk f lung cancer ges up. Fr nw, smkers shuld nt take beta-cartene supplements (University f Maryland Medical Center). HIV and Aids - significant increases in risk f lung cancer have been reprted in research studies cnducted amng peple with HIV and Aids even after accunting fr smking, althugh ne study shwed an assciatin in men nly Chlamydia Pneumniae - peple with antibdies t Chlamydia pneumniae have shw an increase in risk fr lung cancer. Chlamydia pneumniae is an infectius bacteria assciated with a number f diseases including pneumnia Systemic Lupus Erythematsus - an increased risk f lung cancer has been shwn in peple with systemic Lupus Erythematsus Klinefelter syndrme Klinefelter syndrme has been shwn t be a risk factr althugh the risk is less than tw-fld Tuberculsis - a systematic review f published studies shwed that the risk fr lung cancer is almst dubled fr peple with a previus diagnsis f tuberculsis (TB), after taking int accunt smking histry. The risk increase persisted fr mre than 20 years after TB diagnsis (MacMillan Cancer Supprt; WebMD; Centers fr Disease Cntrl and Preventin; Cancer Research UK; United States Envirnmental Prtectin Agency). Signs and Symptms f Lung Cancer Lung cancer typically desn't cause signs and symptms in its earliest stages. Signs and symptms f lung cancer typically ccur nly when the disease is advanced. Signs and symptms f lung cancer may include: a new cugh that desn't g away changes in a chrnic cugh r smker's cugh a cugh that gets wrse r des nt g away cughing up bld, even a small amunt shrtness f breath r wheezing cnstant chest pain especially when cughing frequent chest infectins, such as pneumnia, r an infectin that des nt g away wheezing harseness swelling f the neck and face fatigue (feeling very tired all the time) Researched and Authred by Prf Michael C Herbst [D Litt et Phil (Health Studies); D N Ed; M Art et Scien; B A Cur; Dip Occupatinal Health] Apprved by Ms Elize Jubert, Chief Executive Officer [BA Scial Wrk (cum laude); MA Scial Wrk] May 2017 Page 7

8 lss f appetite lsing weight withut trying bne pain headache (May Clinic; Canadian Cancer Sciety; NIH Senir Health). Diagnsis f Lung Cancer The fllwing are used t diagnsed cancer f the lung: Medical histry - t find ut if lung cancer may be present, the dctr evaluates a persn's medical histry, smking histry, his/her expsure t envirnmental and ccupatinal substances, and family histry f cancer. Physical examinatin - the dctr als perfrms a physical exam and may rder a test t take an image f the chest r ther tests. Seeing a spt n an image is usually hw a dctr first suspects that lung cancer may be present. Sputum cytlgy - if lung cancer is suspected, the dctr may rder a test called a sputum cytlgy. This is a simple test where a dctr examines a sample f mucus cells cughed up frm the lungs under a micrscpe t see if cancer is present. Bipsy - but t cnfirm the presence f lung cancer, the dctr must examine fluid r tissue frm the lung. This is dne thrugh a bipsy - the remval f a small sample f fluid r tissue fr examinatin under a micrscpe by a pathlgist t cnfirm the presence f lung cancer. Brnchscpy a prcedure t cllect cells r small samples f tissues frm the airways and lungs. The dctr inserts a brnchscpe, a thin, lighted tube, int the muth r nse and dwn thrugh the windpipe t lk int the airways t cllect any samples f tissue cells if needed. Needle aspiratin - the dctr numbs the chest area and inserts a thin needle thrugh the chest wall int the tumur t remve a sample f tissue. Thracentesis - using a needle, the dctr remves a sample f the fluid that surrunds the lungs t check fr cancer cells. Thractmy - surgery t pen the chest is smetimes needed t diagnse lung cancer. This prcedure is a majr peratin perfrmed in a hspital. Imaging tests - dctrs use imaging methds such as a spiral Cmputerised Tmgraphy (CT) scan als cmmnly knwn as helical C) r a Psitrn Emissin Tmgraphy (PET) scan t lk fr signs f cancer. A CT scan is a series f detailed pictures f areas inside the bdy. A PET scan is a cmputerised image f the metablic activity f bdy tissues. Other tests - this includes remval f lymph ndes fr examinatin under a micrscpe t check fr cancer cells. Lymph ndes are small, bean-shaped structures fund thrughut the bdy that filter substances in a fluid called lymph and help fight infectin and disease. (NIH Senir Health; WebMD). Researched and Authred by Prf Michael C Herbst [D Litt et Phil (Health Studies); D N Ed; M Art et Scien; B A Cur; Dip Occupatinal Health] Apprved by Ms Elize Jubert, Chief Executive Officer [BA Scial Wrk (cum laude); MA Scial Wrk] May 2017 Page 8

9 Staging f Lung Cancer Staging is the prcess f finding ut hw far a cancer has spread. This is imprtant because treatment ptins and utlk fr recvery and survival depend n the cancer's stage. Staging f lung cancer uses a system created by the American Jint Cmmittee n Cancer (AJCC). The TNM system The TNM system fr staging cntains 3 key pieces f infrmatin: T describes the size f the primary tumur, measured in centimetres (cm), and whether the cancer has spread t rgans next t the tumur N describes the extent f spread t nearby (reginal) lymph ndes M indicates whether the cancer has metastasised (spread) t ther rgans f the bdy Numbers r letters appear after T, N, and M t prvide mre details abut each f these factrs: the numbers 0 thrugh 4 indicate increasing severity the letter X means cannt be assessed because the infrmatin is nt available the letters is mean carcinma in situ, which means the tumur is cntained within the tp layer f anal tissue and has nt yet reached deeper layers f tissue TX T0 Tis T1 T2 T3 T4 primary tumur cannt be assessed, r tumur prven by the presence f malignant cells in sputum r brnchial washings but nt visualised by imaging r brnchscpy n evidence f primary tumur carcinma in situ tumur 3cm r less in greatest dimesin, surrunded by lung r visceral pleura, withut brnchscpic evidence f invasin mre prximal than the lbar brnchus tumur with any f the fllwing features f size r extent: mre than 3cm in greatest dimensin invlving main brnchus, 2cm r mre distal t the carina invading the visceral pleura assciated with atelectasis r bstructive pneumnitis that extends t the hilar regin (area between the tw lungs) but des nt invlve the entire lung tumur f any size that: directly invades the chest wall (including superir sulcus tumurs), diaphragm, mediastinal r parietal pericardium is lcated in the main brnchus less than 2cm distal t the carina but withut invlvement f the carina is assciated with atelectasis r bstructive penumnitis f the entire lung tumur f any size that: invades the mediastinum, heart, great vessels, trachea,esphagus, vertebral bdy r carina is assciated with a malignant pleural effusin Reginal Lymph Ndes (N) NX reginal lymph ndes cannt be assessed Researched and Authred by Prf Michael C Herbst [D Litt et Phil (Health Studies); D N Ed; M Art et Scien; B A Cur; Dip Occupatinal Health] Apprved by Ms Elize Jubert, Chief Executive Officer [BA Scial Wrk (cum laude); MA Scial Wrk] May 2017 Page 9

10 N0 N1 N2 N3 n reginal lymph ndes metastasis metastasis in ipsilateral peribrnchial and/r ipsilateral hilar lymph ndes, including direct extensin metastasis in ipsilateral mediastinal and/r subcarinal lymph nde(s) metastasis in cntralateral mediastinal, cntralateral hilar, ipsilateral r cntralateral scalene r supraclavicular lymph nde(s) Distant Metastases (M) MX presence f distant metastasis cannt be assessed M0 n distant metastasis M1 distant metastasis Stage Gruping Occult TX N0 M0 Stage 0 Tis N0 M0 Stage I T1 N0 M0 T2 N0 M0 Stage II T1 N1 M0 T2 N1 M0 Stage IIIA T1 N2 M0 T2 N2 M0 T3 N0 M0 T3 N1 M0 T3 N2 M0 Stage IIIB Any T N3 M0 T4 Any N M0 Stage IV (CTSN) Any T Any N M1 Where Lung Cancer May Spread t in the Bdy In the event f lung cancer spreading t ther parts f the bdy, it may spread as indicated in the bld sectin belw: Cancer Type: Bladder Breast Cln Clrectal Kidney Lung Melanma Ovary Main Sites f Metastasis (Spread) Bne, liver, lung Bne, brain, liver, lung Liver, lung Liver, lung, peritneum (lining f abdmen) Adrenal gland, bne, brain, liver, lung Adrenal gland, bne, brain, liver, ther lung Bne, brain, liver, lung, skin, muscle Liver, lung, peritneum (lining f abdmen) Researched and Authred by Prf Michael C Herbst [D Litt et Phil (Health Studies); D N Ed; M Art et Scien; B A Cur; Dip Occupatinal Health] Apprved by Ms Elize Jubert, Chief Executive Officer [BA Scial Wrk (cum laude); MA Scial Wrk] May 2017 Page 10

11 Pancreas Prstate Stmach Thyrid Uterus Nn-melanma skin cancer (Natinal Cancer Institute) Liver lung, peritneum (lining f abdmen) Adrenal gland, bne, liver, lung Liver, lung, peritneum (lining f abdmen), varies Bne, liver, lung Bner, liver, lung, peritneum (lining f abdmen), vagina Very rare: lymph ndes, lung, bne (if in head/neck regin) Treatment f Lung Cancer The type f treatment a patient will receive fr lung cancer depends n several factrs, including: the type f lung cancer (nn-small cell r small cell) the size and psitin f the cancer hw far advanced the cancer is (the stage) patient s verall health Deciding what treatment is best can be difficult. The cancer team will make recmmendatins, but the final decisin will be that f the patient. Treatment ptins include: surgery raditherapy chemtherapy Small Cell Lung Cancer (SCLC) Fr mst patients with small cell lung cancer, current treatments d nt cure the cancer. Regardless f stage, the current prgnsis fr patients with SCLC is pr despite imprvements in diagnsis and therapy made during the past 25 years. Withut treatment, SCLC has the mst aggressive clinical curse f any type f pulmnary tumur, with median survival frm diagnsis f nly 2 t 4 mnths. Abut 10% f the ttal ppulatin f SCLC patients remains free f disease during the 2 years frm the start f therapy, which is the time perid during which mst relapses ccur. Even these patients, hwever, are at risk f dying frm lung cancer (bth small and nn-small cell types).] The verall survival at 5 years is 5% t 10%. (NHS Chices; Natinal Cancer Institute) Nn-Small Cell Lung Cancer Nine types f standard treatment are used: Surgery Five types f surgery are used t treat lung cancer: Wedge resectin remval f a tumur and sme f the nrmal tissue arund it. When a slightly larger amunt f tissue is taken, it is called a segmental resectin. Researched and Authred by Prf Michael C Herbst [D Litt et Phil (Health Studies); D N Ed; M Art et Scien; B A Cur; Dip Occupatinal Health] Apprved by Ms Elize Jubert, Chief Executive Officer [BA Scial Wrk (cum laude); MA Scial Wrk] May 2017 Page 11

12 Segmental resectin f the lung - part f the lung lbe cntaining the cancer and a slightly larger amunt f healthy tissue arund it is remved than in the case f a wedge resectin Lbectmy remval f a whle lbe (sectin) f the lung Pneumnectmy remval f the whle lung Sleeve resectin remve f part f the brnchus Even if the dctr remves all the cancer that can be seen at the time f the surgery, sme patients may be given chemtherapy r radiatin therapy after surgery t kill any remaining cancer cells. Treatment given after the surgery t lwer the risk f recurrence, is called adjuvant therapy. Radiatin therapy - radiatin therapy is a cancer treatment that uses high-energy x-rays r ther types f radiatin t kill cancer cells r keep them frm grwing. There are tw types f radiatin therapy. External radiatin therapy uses a machine utside the bdy t send radiatin tward the cancer. Internal radiatin therapy uses a radiactive substance sealed in needles, seeds, wires, r catheters that are placed directly int r near the cancer. Radisurgery - is a methd f delivering radiatin directly t the tumur with little damage t healthy tissue. It des nt invlve surgery and may be used t treat certain tumurs in patients wh cannt have surgery. The way the radiatin therapy is given depends n the type and stage f the cancer being treated. It als depends n where the cancer is fund. Fr tumurs in the airways, radiatin is given directly t the tumur thrugh an endscpe. Chemtherapy - chemtherapy is a cancer treatment that uses drugs t stp the grwth f cancer cells, either by killing the cells r by stpping them frm dividing. When chemtherapy is taken by muth r injected int a vein r muscle, the drugs enter the bldstream and can reach cancer cells thrughut the bdy (systemic chemtherapy). When chemtherapy is placed directly int the cerebrspinal fluid, an rgan, r a bdy cavity such as the abdmen, the drugs mainly affect cancer cells in thse areas (reginal chemtherapy). The way the chemtherapy is given depends n the type and stage f the cancer being treated. Targeted therapy - targeted therapy is a type f treatment that uses drugs r ther substances t identify and attack specific cancer cells withut harming nrmal cells. Mnclnal antibdies and tyrsine kinase inhibitrs are tw types f targeted therapy being used in the treatment f nn-small cell lung cancer. Mnclnal antibdy therapy - is a cancer treatment that uses antibdies made in the labratry frm a single type f immune system cell. These antibdies can identify substances n cancer cells r nrmal substances that may help cancer cells grw. The antibdies attach t the substances and kill the cancer cells, blcking its grwth, r keeping it frm spreading. Mnclnal antibdies are given by infusin. It may be used alne r t carry drugs, txins, r radiactive material directly t cancer cells. Mnclnal antibdies used t treat nn-small cell lung cancer include bevacizumab and cetuximab. Bevacizumab binds t vascular endthelial grwth factr (VEGF) and may Researched and Authred by Prf Michael C Herbst [D Litt et Phil (Health Studies); D N Ed; M Art et Scien; B A Cur; Dip Occupatinal Health] Apprved by Ms Elize Jubert, Chief Executive Officer [BA Scial Wrk (cum laude); MA Scial Wrk] May 2017 Page 12

13 prevent the grwth f new bld vessels that tumurs need t grw. Cetuximab binds t epidermal grwth factr receptr (EGFR) and wrks t stp cancer cells frm grwing and dividing. Tyrsine kinase inhibitrs - are targeted therapy drugs that blck signals needed fr tumurs t grw. Tyrsine kinase inhibitrs may be used with ther anticancer drugs as adjuvant therapy. Tyrsine kinase inhibitrs are used t treat nn-small cell lung cancer and include erltinib and gefitinib. They are types f epidermal grwth factr receptr (EGFR) tyrsine kinase inhibitrs. Criztinib is a type f tyrsine kinase inhibitr that is used t treat nn-small cell lung cancer with certain gene changes. Immuntherapy - The US Fd and Drug Administratin has apprval the anti PD-1 immuntherapy pembrlizumab (Keytruda), in cmbinatin with pemetrexed and carbplatin, fr patients with untreated metastatic nn-squamus nn small-cell lung cancer (NSCLC). The apprval was based n results f a chrt frm KEYNOTE-021, an pen-label, multichrt trial. The study cmpared 4 cycles f pemetrexed and carbplatin in 63 patients vs pemetrexed/carbplatin plus 200 mg pembrlizumab intravenusly every 3 weeks in 60 patients until prgressin r unacceptable txicity. Eligible participants had lcally advanced r metastatic nn-squamus NSCLC and had nt previusly received any systemic therapy. Patients in either arm culd als receive pemetrexed as maintenance therapy at the investigatr s discretin. Patients were randmized by PD-L1 tumur expressin (tumur prprtin scre [TPS] < 1% vs TPS 1%). Patients wh received pembrlizumab had imprved verall respnse rates and prgressin-free survival. The verall respnse rate was 55% in patients wh received pembrlizumab plus chemtherapy vs 29% in thse wh received chemtherapy alne (P =.0032). The median prgressin-free survival was 13 mnths with pembrlizumab vs 8.9 mnths fr chemtherapy alne fr a hazard rati f 0.53 (95% CI, ; P =.0205). The verall respnse rate amng patients with TPS < 1% was 57% in the pembrlizumabtreated grup vs 13% in the chemtherapy-alne grup. In patients with TPS 1%, the verall respnse rate was 54% in the pembrlizumab-treated grup vs 38% in the chemtherapy-alne arm Serius adverse events in the pembrlizumab arm ccurred in 41% f patients vs 28% in thse wh nly received chemtherapy. The mst cmmn adverse events f any grade amng patients wh received pembrlizumab were cnstipatin (51%), fatigue (71%), and nausea (68%). Grade 3/4 adverse events included dyspnea and fatigue (3.4% each), and diarrhea, nausea, rash, and vmiting (1.7% each). Ten percent f patients discntinued pembrlizumab due t adverse events, with acute kidney injury (3.4%) as the mst cmmn cause. Pembrlizumab can als cause immune-mediated txicities including clitis, endcrinpathies, hepatitis, nephritis, and pneumnitis. Based n the severity, pembrlizumab shuld be either discntinued r withheld, and patients shuld be given crticsterids if needed. Researched and Authred by Prf Michael C Herbst [D Litt et Phil (Health Studies); D N Ed; M Art et Scien; B A Cur; Dip Occupatinal Health] Apprved by Ms Elize Jubert, Chief Executive Officer [BA Scial Wrk (cum laude); MA Scial Wrk] May 2017 Page 13

14 The recmmended dse f pembrlizumab fr NSCLC is 200 mg IV every 3 weeks until prgressin, unacceptable txicity, r fr 2 years in patients withut disease prgressin. Laser therapy - laser therapy is a cancer treatment that uses a laser beam (a narrw beam f intense light) t kill cancer cells. Phtdynamic therapy (PDT) - is a treatment that uses a drug, called a phtsensitiser r phtsensitising agent, and a particular type f light. When phtsensitisers are expsed t a specific wavelength f light, they prduce a frm f xygen that kills nearby cells. Each phtsensitiser is activated by light f a specific wavelength. This wavelength determines hw far the light can travel int the bdy. Thus, dctrs use specific phtsensitisers and wavelengths f light t treat different areas f the bdy with PDT. Phtdynamic therapy causes little damage t healthy tissue. It is used mainly t treat tumurs n r just under the skin r in the lining f internal rgans. When the tumur is in the airways, PDT is given directly t the tumur thrugh an endscpe. Crysurgery - crysurgery is a treatment that uses an instrument t freeze and destry abnrmal tissue, such as carcinma in situ. This type f treatment is als called crytherapy. Fr tumurs in the airways, crysurgery is dne thrugh an endscpe. Electrcautery - electrcautery is a treatment that uses a prbe r needle heated by an electric current t destry abnrmal tissue. Fr tumurs in the airways, electrcautery is dne thrugh an endscpe. Watchful waiting - watchful waiting is clsely mnitring a patient s cnditin withut giving any treatment until symptms appear r change. This may be dne in certain rare cases f nn-small cell lung cancer. (Natinal Cancer Institute; Medline Plus; CancerNetwrk). CANCER TREATMENT REGIMENS (Revised 4/2015) 2015 Haymarket Media, Inc. Clinical Trials: The NCCN recmmends cancer patient participatin in clinical trials as the gld standard fr treatment. Cancer therapy selectin, dsing, administratin, and the management f related adverse events can be a cmplex prcess that shuld be handled by an experienced healthcare team. Clinicians must chse and verify treatment ptins based n the individual patient; drug dse mdificatins and supprtive care interventins shuld be administered accrdingly. The cancer treatment regimens belw may include bth U.S. Fd and Drug Administratin-apprved and unapprved indicatins/regimens. These regimens are nly prvided t supplement the latest treatment strategies. These Guidelines are a wrk in prgress that may be refined as ften as new significant data becmes available. The NCCN Guidelines are a cnsensus statement f its authrs regarding their views f currently accepted appraches t treatment. Any clinician seeking t apply r cnsult any NCCN Guidelines is expected t use independent medical judgment in the cntext f individual clinical circumstances t determine any patient's care r treatment. The Natinal Cmprehensive Cancer Netwrk makes n warranties f any kind whatsever regarding their cntent, use, r applicatin and disclaims any respnsibility fr their applicatin r use in any way. Nn-Small Cell Lung Cancer (NSCLC) Nte: All recmmendatins are Categry 2A unless therwise indicated. Chemtherapy Regimens Fr Neadjuvant and Adjuvant Therapy 1 REGIMEN DOSING Days 1 and 8: Cisplatin 50mg/m 2 IV plus Researched and Authred by Prf Michael C Herbst [D Litt et Phil (Health Studies); D N Ed; M Art et Scien; B A Cur; Dip Occupatinal Health] Apprved by Ms Elize Jubert, Chief Executive Officer [BA Scial Wrk (cum laude); MA Scial Wrk] May 2017 Page 14

15 vinrelbine 2 4 etpside 3 vinblastine 3 gemcitabine 5 dcetaxel 6 pemetrexed 7,8 CANCER TREATMENT REGIMENS Days 1, 8, 15 and 22: Vinrelbine 25mg/m 2 IV. Repeat cycle every 4 weeks fr 4 cycles. OR Day 1: Cisplatin 100mg/m 2 IV plus Days 1, 8, 15 and 22: Vinrelbine 30mg/m 2 IV. Repeat cycle every 4 weeks fr 4 cycles. OR Day 1: Cisplatin 75 80mg/m 2 plus Days 1 + 8: Vinrelbine 25 30mg/m 2. Repeat every 3 weeks fr 4 cycles. Day 1: Cisplatin 100mg/m 2 IV plus Days 1 3: Etpside 100mg/m 2 IV. Repeat cycle every 4 weeks fr 4 cycles. Days 1, 22, 43, 64: Cisplatin 80mg/m 2 IV. Days 1, 8, 15, 22, 29, and then every 2 weeks after day 43:Vinblastine 4 mg/m 2. Repeat every 3 weeks fr 4 cycles. Day 1: Cisplatin 75mg/m 2 IV plus Days 1 and 8: Gemcitabine 1,250mg/m 2 IV. Repeat cycle every 3 weeks. Day 1: Dcetaxel 75mg/m 2 IV + cisplatin 75mg/m 2 IV. Repeat every 3 weeks fr 4 cycles. Day 1: Cisplatin 75mg/m 2 IV + pemetrexed 500mg/m 2 IV. * Repeat every 3 weeks fr 4 cycles. Fr patients with cmrbidities r patients nt able t tlerate cisplatin 1 Paclitaxel + carbplatin 9 Day 1: Paclitaxel 200mg/m 2 IV + carbplatin AUC=6 IV. Repeat cycle every 3 weeks fr 4 cycles. Cncurrent Chemtherapy/Raditherapy (RT) 1 etpside 10, (preferred regimen) vinblastine (preferred regimen) 11 Carbplatin + pemetrexed (nnsquamus) 12 pemetrexed (nnsquamus) 7,8 Days 1, 8, 29 and 36: Cisplatin 50mg/m 2 IV plus Days 1 5 and 29 33: Etpside 50mg/m 2 IV plus Cncurrent thracic raditherapy 1.8Gy/day fr 5 days/week (ttal dse, 61Gy). Days 1 and 29: Cisplatin 100mg/m 2 IV plus Days 1, 8, 15, 22 and 29: Vinblastine 5mg/m 2 IV with cncurrent thracic raditherapy (ttal dse, 60Gy). Day 1: Carbplatin AUC 5 IV plus Day 1: Pemetrexed 500 mg/m 2 IV with cncurrent thracic raditherapy. Repeat every 3 weeks fr 4 cycles. Day 1: Cisplatin 75 mg/m 2 IV. Day 1: Pemetrexed 500 mg/m 2 IV with cncurrent thracic raditherapy. Repeat every 3 weeks fr 3 cycles. Sequential Chemtherapy/Raditherapy (RT) 1 vinblastine 11 Days 1 and 29: Cisplatin 100mg/m 2 IV. Days 1, 8, 15, 22 and 29: Vinblastine 5mg/m 2 IV; fllwed bythracic raditherapy with 60Gy in 30 fractins beginning n Day 50. Researched and Authred by Prf Michael C Herbst [D Litt et Phil (Health Studies); D N Ed; M Art et Scien; B A Cur; Dip Occupatinal Health] Apprved by Ms Elize Jubert, Chief Executive Officer [BA Scial Wrk (cum laude); MA Scial Wrk] May 2017 Page 15

16 Paclitaxel + carbplatin 13 CANCER TREATMENT REGIMENS Day 1: Paclitaxel 200mg/m 2 IV ver 3 hurs + carbplatin AUC=6 IV ver 1 hur. Repeat every 3 weeks fr 2 cycles; fllwed by thracic raditherapy 63Gy beginning n Day 42. Cncurrent Chemtherapy/Raditherapy (RT) Fllwed by Chemtherapy 1 Paclitaxel + carbplatin 13 etpside 10 Day 1 (weekly): Paclitaxel 45 50mg/m 2 IV and carbplatin AUC=2 IV. Cncurrent thracic raditherapy; fllwed by tw additinal cycles f paclitaxel 200mg/m 2 IV and carbplatin AUC=6 IV. Days 1, 8, 29, and 36: Cisplatin 50mg/m 2 IV. Days 1 5, 29 33: Etpside 50mg/m 2 IV with cncurrent thracic raditherapy; fllwed by tw additinal cycles f cisplatin 50mg/m 2 IV and etpside 50mg/m 2 IV. Systemic Therapy fr Advanced Disease 1 The drug regimen with the highest likelihd f benefit, with txicity deemed acceptable t bth the physician and the patient, shuld be given as initial therapy fr advanced lung cancer. Stage, weight lss, perfrmance status (PS), and gender predict survival. Platinum-based chemtherapy prlngs survival, imprves symptm cntrl, and yields superir quality f life cmpared t best supprtive care. Histlgy f NSCLC is imprtant in the selectin f systemic therapy. New agent/platinum cmbinatins have generated a plateau in verall respnse rate ( 25% 35%), time t prgressin (4 6 mnths), median survival (8 10 mnths), 1-year survival rate (30% 40%), and 2-year survival rate (10% 15%) in fit patients. Unfit patients f any age (PS 3 4) d nt benefit frm cyttxic treatment, except erltinib fr thse wh are epidermal grwth factr receptr (EGFR) mutatin-psitive. Principals f Maintenance Therapy 1 Cntinuatin maintenance refers t the use f at least ne f the agents given in first line, beynd 4 t 6 cycles, in the absence f disease prgressin. Switch maintenance refers t the initiatin f a different agent, nt included as part f the first-line regimen, in the absence f disease prgressin, after 4 t 6 cycles f initial therapy. Cntinuatin Maintenance: Bevacizumab and cetuximab given in cmbinatin with chemtherapy shuld be cntinued until evidence f disease prgressin r unacceptable txicity, as per the design f the clinical trials supprting their use. Cntinuatin f bevacizumab after 4 6 cycles f platinum-dublet chemtherapy and bevacizumab (categry 1). Cntinuatin f cetuximab after 4 6 cycles f cisplatin, vinrelbine, and cetuximab (categry 1). Cntinuatin f pemetrexed after 4 6 cycles f cisplatin and pemetrexed chemtherapy, fr patients with histlgies ther than squamus cell carcinma (categry 1). Cntinuatin f bevacizumab + pemetrexed after 4 6 cycles f bevacizumab, pemetrexed, cisplatin/carbplatin, fr patients with histlgies ther than squamus cell carcinma. Cntinuatin f gemcitabine after 4 6 cycles f platinum-dublet chemtherapy (categry 2B). Switch Maintenance: Tw studies have shwn a benefit in prgressin-free and verall survival with the initiatin f pemetrexed r erltinib after first-line chemtherapy, in patients withut disease prgressin after 4 6 cycles f therapy. Initiatin f pemetrexed after 4 6 cycles f first-line platinum-dublet chemtherapy fr patients with histlgies ther than squamus cell carcinma (categry 2B). Initiatin f erltinib after 4 6 cycles f first-line platinum-dublet chemtherapy (categry 2B). Initiatin f dcetaxel after 4 6 cycles f first-line platinum-dublet chemtherapy in patients with squamus cell carcinma (categry 2B). Clse surveillance f patients withut therapy is a reasnable alternative t maintenance. Principles f Third-Line Therapy 1 Researched and Authred by Prf Michael C Herbst [D Litt et Phil (Health Studies); D N Ed; M Art et Scien; B A Cur; Dip Occupatinal Health] Apprved by Ms Elize Jubert, Chief Executive Officer [BA Scial Wrk (cum laude); MA Scial Wrk] May 2017 Page 16

17 CANCER TREATMENT REGIMENS If nt already given, ptins fr patients with PS 0 2 include dcetaxel, pemetrexed (nnsquamus), erltinib, r gemcitabine (categry 2B fr all ptins). Cntinuatin After Disease Prgressin 1 With the exceptin f targeted agents (erltinib, gefitinib, afatinib, criztinib, ceritinib) in patients with EGFR-sensitizing mutatins r ALK rearrangements wh have experienced bjective regressins with targeted therapy, n agent shuld be cntinued after disease prgressin has been dcumented except in selected situatins. (refer t discussin sectin f NCCN Guidelines fr Nn-Small Cell Lung Cancer v ) Systemic Treatment Optins fr Patients with NSCLC 1, Cisplatin Carbplatin 17,18 23 Paclitaxel 14,17,18,20 23 Dcetaxel 5,6,19,23,24 Vinrelbine 6,20,21 Gemcitabine 5,16,18 20,24 Etpside 17 lrintecan 20 Vinblastine Mitmycin Ifsfamide 23 Pemetrexed 7,8 Erltinib 25 Bevacizumab 26 Cetuximab 27 Albumin-bund paclitaxel Criztinib 31 Afatinib 32 Ceritinib 33 Ramucirumab 34 Nivlumab 35 First-Line Systemic Therapy fr Advanced Disease 1 Bevacizumab carbplatin + paclitaxel 26,36 Cetuximab + cisplatin + vinrelbine 27 Erltinib 37,38 paclitaxel 19 gemcitabine 19 dcetaxel 6 vinrelbine 6 Carbplatin + paclitaxel 19 Pemetrexed + cisplatin 24,39 Day 1: Paclitaxel 200mg/m 2 IV Day 1: Carbplatin AUC=6 IV. Repeat every 3 weeks fr 6 cycles. Day 1: Bevacizumab 15mg/kg IV every 3 weeks until disease prgressin. Day 1: Cetuximab 400mg/m 2 IV + cisplatin 80mg/m 2 IV, plus Days 1 and 8: Vinrelbine 25mg/m 2 IV, plus Day 8: Cetuximab 250mg/m 2 IV nce weekly. Repeat every 3 weeks fr 6 cycles. Day 1: Erltinib 150mg PO nce daily; fllwing 4 cycles f platinumbased chemtherapy. Day 1: Paclitaxel 135mg/m 2 IV ver 24 hurs Day 2: Cisplatin 75mg/m 2 IV. Repeat cycle every 3 weeks. Day 1: Cisplatin 100mg/m 2 IV Days 1, 8 and 15: Gemcitabine 1,000mg/m 2 IV. Repeat cycle every 4 weeks. Day 1: Cisplatin 75mg/m 2 IV + dcetaxel 75mg/m 2 IV. Repeat cycle every 3 weeks. Day 1: Cisplatin 100mg/m 2 IV Days 1, 8, 15 and 22: Vinrelbine 25mg/m 2 IV ver 10 minutes. Repeat cycle every 4 weeks. Day 1: Carbplatin AUC=5 6 IV Day 1: Paclitaxel 225mg/m 2 IV ver 3 hurs. Repeat cycle every 3 weeks. Day 1: Pemetrexed 500mg/m 2 IV + cisplatin 75mg/m 2 IV. Repeat cycle every 3 weeks. Criztinib 40# Criztinib 250mg PO twice daily. ** Afatinib 32 Afatinib 40mg PO nce daily. Researched and Authred by Prf Michael C Herbst [D Litt et Phil (Health Studies); D N Ed; M Art et Scien; B A Cur; Dip Occupatinal Health] Apprved by Ms Elize Jubert, Chief Executive Officer [BA Scial Wrk (cum laude); MA Scial Wrk] May 2017 Page 17

18 CANCER TREATMENT REGIMENS Principals f First-Line Therapy 1 Bevacizumab + chemtherapy r chemtherapy alne is indicated in patients with PS 0 1 with advanced r recurrent NSCLC. Bevacizumab shuld be given until disease prgressin. Cetuximab + vinrelbine/cisplatin is an ptin fr patients with PS 0 1 (categry 2B). Erltinib is recmmended as a first-line therapy in patients with sensitizing EGFR mutatins and shuld nt be given as first-line therapy t patients negative fr these EGFR mutatins r with unknwn EGFR status. Afatinib is indicated fr select patients with sensitizing EGFR mutatins. Criztinib is indicated fr select patients with ALK rearrangements. There is superir efficacy and reduced txicity fr cisplatin/pemetrexed in patients with nnsquamus histlgy cmpared with cisplatin/gemcitabine. There is superir efficacy fr cisplatin/gemcitabine in patients with squamus histlgy, in cmparisn t cisplatin/pemetrexed. Tw drug regimens are preferred; a third cyttxic drug increases respnse rate but nt survival. Single-agent therapy r platinum-based cmbinatins are a reasnable alternative in PS 2 patients r the elderly. Cisplatin r carbplatin have been prven effective in cmbinatin with any f the fllwing agents: paclitaxel, dcetaxel, gemcitabine, etpside, vinblastine, vinrelbine, pemetrexed, r albumin-bund paclitaxel. New agent/nn-platinum cmbinatins are reasnable alternatives if available data shw activity and tlerable txicity (e.g., gemcitabine/dcetaxel, gemcitabine/vinrelbine). Respnse assessment after 1 2 cycles, then every 2 4 cycles. Subsequent Secnd-Line Systemic Therapy fr Advanced Disease 1 Dcetaxel 23 Pemetrexed 7 Erltinib 25 Ceritinib 33# Ramucirumab + dcetaxel 34 Afatinib 32 Nivlumab 35 Day 1: Dcetaxel 75mg/m 2 IV. Repeat cycle every 3 weeks. Day 1: Pemetrexed 500mg/m 2 IV. Repeat cycle every 3 weeks. Erltinib 150mg PO nce daily. Ceritinib 750mg PO nce daily. Day 1: Ramucirumab 10mg/kg IV + dcetaxel 75mg/m 2 IV. Repeat cycle every 3 weeks. Afatinib 40mg PO nce daily. Nivlumab 3mg/kg IV ver 60 minutes every 2 weeks. Principles f Subsequent Therapy 1 In patients wh have experienced disease prgressin either during r after first-line therapy, single-agent dcetaxel, pemetrexed, r erltinib are established secnd-line agents. Dcetaxel is superir t vinrelbine r ifsfamide. Pemetrexed is cnsidered equivalent t dcetaxel with less txicity in patients with adencarcinma and large cell carcinma. Ramucirumab + dcetaxel imprves survival when cmpared t dcetaxel alne. Erltinib is superir t best supprtive care. Afatinib is indicated fr select patients with sensitizing EGFR mutatins. Ceritinib is indicated fr patients with ALK rearrangements wh have disease prgressin n r are intlerant t criztinib. If nt already given, ptins fr patients with PS 0 2 include dcetaxel, pemetrexed (nnsquamus), erltinib, r gemcitabine (categry 2B fr all ptins). Cntinuatin After Disease Prgressin 1 With the exceptin f targeted agents (erltinib, gefitinib, afatinib, criztinib) in patients with Researched and Authred by Prf Michael C Herbst [D Litt et Phil (Health Studies); D N Ed; M Art et Scien; B A Cur; Dip Occupatinal Health] Apprved by Ms Elize Jubert, Chief Executive Officer [BA Scial Wrk (cum laude); MA Scial Wrk] May 2017 Page 18

19 CANCER TREATMENT REGIMENS EGFR-sensitizing mutatins r ALK rearrangements wh have experienced bjective regressins with targeted therapy, n agent shuld be cntinued after disease prgressin has been dcumented except in selected situatins (refer t discussin sectin f NCCN Guidelines fr Nn-Small Cell Lung Cancer v ). Small Cell Lung Cancer (SCLC) Chemtherapy as Primary r Adjuvant Therapy Limited Stage (maximum f 4 6 cycles) 1 etpside Carbplatin + etpside 44 Day 1: Cisplatin 60mg/m 2 IV plus Days 1 3: Etpside 120mg/m 2 IV. Repeat cycle every 3 weeks fr at least 4 cycles. OR Day 1: Cisplatin 80mg/m 2 IV plus Days 1 3: Etpside 100mg/m 2 IV. Repeat every 4 weeks fr 4 6 cycles. Day 1: Carbplatin AUC=5 6 IV plus Days 1 3: Etpside 100mg/m 2 IV. Repeat every 3 weeks fr 4 6 cycles. Extensive Stage (maximum f 4 6 cycles) 1 etpside irintecan 41,48,49 Carbplatin + irintecan 50 Carbplatin + etpside 51 Subsequent Chemtherapy Relapse <2 3 mnths, PS Paclitaxel 18,52 Dcetaxel 53 Day 1: Cisplatin 75 80mg/m 2 IV Days 1 3: Etpside mg/m 2 IV. Repeat every 3 weeks fr 4 6 cycles. OR Days 1 3: Cisplatin 25mg/m 2 IV + etpside 100mg/m 2 IV. Repeat cycle every 3 weeks fr 4-6 cycles. Day 1: Cisplatin 60mg/m 2 IV Days 1, 8 and 15: Irintecan 60mg/m 2 IV. Repeat cycle every 4 weeks fr 4 cycles. OR Day 1 and 8: Cisplatin 30mg/m 2 IV Day 1 and 8: Irintecan 65mg/m 2 IV. Repeat every 3 weeks fr 4 6 cycles. Day 1: Carbplatin AUC=5 IV plus Days 1, 8 and 15: Irintecan 50mg/m 2 IV. Repeat cycle every 4 weeks fr 4 6 cycles. Day 1: Carbplatin AUC=5 6 IV. Days 1 3: Etpside 100mg/m 2 IV. Repeat every 4 weeks fr 4 6 cycles. Day 1: Paclitaxel 175mg/m 2 IV ver 3 hurs plus Day 1: Cisplatin 80mg/m 2 IV. Repeat every 3 weeks fr at least 2 cycles. OR Day 1: Paclitaxel 80mg/m 2 IV ver 1 hur. Repeat every week fr 6 weeks, fllwed by a 2-week break. Day 1: Dcetaxel 100mg/m 2 IV ver 1 hur. Repeat every 21 days. Researched and Authred by Prf Michael C Herbst [D Litt et Phil (Health Studies); D N Ed; M Art et Scien; B A Cur; Dip Occupatinal Health] Apprved by Ms Elize Jubert, Chief Executive Officer [BA Scial Wrk (cum laude); MA Scial Wrk] May 2017 Page 19