1. SMALL CELL LUNG CANCER 2007 BP HIGGINS MD FRCPC CFPRCC

2. SMALL CELL LUNG CANCER  DECLINING INCIDENCE 15%  RAPIDLY PROLIFERATING TUMOR  CHEMOTHERAPY SENSITIVE  CENTRAL ENDOBRONCHIAL LESION (SUBMUCOSAL)

4. SMALL CELL  NEUROENDOCRINE DIFFERENTIATION  SPECTRUM CARCINOID-ATYPICAL CARCINOID-SMALL CELL  IHC KERATIN+ CD56+ TTF1+ SYNAPTOPHYSIN+

8. STAGING  LIMITED :TUMOR THAT CAN BE ENCOMPASSED WITHIN A SINGLE REASONABLE RADIATION PORT 1/3  EXTENSIVE :ALL THE REST 2/3

9. STAGING  CBC BIOCHEMICAL PROFILE(LDH)  CT THORAX(LIVER/ADRENALS)  BONE SCAN  CT/MRI BRAIN

10. TREATMENT  LIMITED DISEASE  ETOPOSIDE/CISPLATIN (GIVE CISPLATIN FIRST) E 100mg/m2 x3d Cisplatin 25mg/m2 x 3d q 21d x 6 cycles

11. TREATMENT  EVANS JCO 1985 CAV vs CAV/EP MEDIAN SURVIVAL 8.0 vs 9.6 m  ROTH JCO 1992 CAV vs CAV/PE vs EP MEDIAN SURVIVAL 8.3 vs 8.1 vs 8.6 m

12. Sundstrom et al. JCO 2002 REGIMENEP 5CYCLES CEV 5 CYCLES MEDIAN SURVIVAL (mos) 14.59.7

13. TREATMENT  2 META-ANALYSES DEMONSTRATE SUPERIORITY OF CISPLATIN CONTAINING REGIMENS  MULTI-DAY CHEMOTHERAPY  5HT3 ANTAGONISTS  HYPOTENSION WITH ETOPOSIDE  ?CARBOPLATIN? Extensive Disease Skarlos Ann Onc 1994 EC vs EP MEDIAN SURVIVAL 11.8 vs 12.5 m

14. TREATMENT LIMITED SCLC  THORACIC RADIATION  ?CONCURRENT vs SEQUENTIAL  PATIENT SELECTION : GOOD PS, AGE, SEX

15. RADIATION JCO 1992 Warde & Payne LOCAL RELAPSE 2 YEARS(%) RADS 40 NO RADS 65 OVERALL SURVIVAL 2 YEARS(%) 2216 Rx MORTALITY (%) 21

16. TIMING OF RADIATION NCIC BR-5 JCO 1993 Murray,N EP/CAV wk3 4000/15 EP/CAV wk15 4000/15 Median Survival(mos) 21 16 2 yr Survival(%) 40 33 5 yr Survival(%) 20 11 Esophagitis (%) 15 7.5

17. RADIATION  JCO 2004 META-ANALYSIS~SMALL BUT SIGNIFICANT BENEFIT IN 2 y SURVIVAL IN FAVOUR OF EARLY RADS(<9 WEEKS) ORR 1.17 p=0.03  ?HYPERFRACTIONATION? (ESOPHAGITIS/INCONVENIENCE)

18. PROPHYLACTIC CRANIAL IRRADIATION (PCI)  5.4% IMPROVEMENT IN 3 YEAR SURVIVAL. NEJM 1999  NEUROPSYCHOLOGIC TOXICITY(MEMORY LOSS)  ATAXIA  FOR COMPLETE RESPONDERS/ EXCELLENT PR  INCIDENCE ~20% AT DIAGNOSIS >50% AT 2 YEARS  ?EXTENSIVE DISEASE

19. ASCO 2007

22. EXTENSIVE SCLC NCIC BR8 JCO 1999 MURRAY,N et al. GOLDIE/COLDMAN DOSE INTENSITY CODE x 6CAV/EP x 6 CR (%) 23 20 OVERALL SURVIVAL (y) 0.98 0.91 Rx Mortality (%) 8.2 0.9

23. EXTENSIVE SCLC  IP vs EP NEJM 2002 n=154  Median Survival 12.8 m vs 9.4 m 2y Survival 19.5% vs 5.2%  JCO 2006 Hanna et al. n=331  IP vs EP RR 48 vs 43.6% MS 9.3 vs 10.2 mos Diarrhea vs Neutropenia

24. Hanna, N. et al. J Clin Oncol; 24:2038-2043 2006 Fig 2. Overall survival

25. Eckardt, J. R. et al. J Clin Oncol; 24:2044-2051 2006 Fig 1. Kaplan-Meier estimates for survival in the intent-to-treat population

26. SECOND LINE Rx  IMPORTANCE OF PROGRESSION FREE INTERVAL  6-12mos  Patient selection  MEDIAN SURVIVAL 2-3mos

27. SECOND LINE Rx  JCO 1999 CAV vs Topotecan  Median survival 25 weeks  1 year survival 14%  (selection!!!!!!!!)  If long DFI consider original regimen  Patient convenience,$

28. SCLC PARANEOPLASTIC SYNDROMES  ACTH 3-7%  ADH 3-15%  LAMBERT-EATON  CEREBELLAR DEGENERATION  NOT HPOA!!!!  SVC OBSTRUCTION  Rx UNDERLYING DISEASE

29. SCLC SUMMARY  LIMITED DISEASE  EP/RADS  RR 65-90%  CR 40-75%  Median survival 18-24mos  5 y survival 20-25%  EXTENSIVE DISEASE  EP/ECARBO/E  RR 60-85%  CR 15-30%  Median survival 6-11mos  5 y survival <2% EJ CANCER 2004

30. SCLC  No Role for DI/DD  2 Drugs = 3 or more  Cisplatin based  4 cycles in ED  ? Targeted Rx ?