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SMALL CELL LUNG CANCER 2007

SMALL CELL LUNG CANCER 2007. BP HIGGINS MD FRCPC CFPRCC. SMALL CELL LUNG CANCER. DECLINING INCIDENCE 15% RAPIDLY PROLIFERATING TUMOR CHEMOTHERAPY SENSITIVE CENTRAL ENDOBRONCHIAL LESION (SUBMUCOSAL). SMALL CELL. NEUROENDOCRINE DIFFERENTIATION

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SMALL CELL LUNG CANCER 2007

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  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)

  3. SMALL CELL • NEUROENDOCRINE DIFFERENTIATION • SPECTRUM CARCINOID-ATYPICAL CARCINOID-SMALL CELL • IHC KERATIN+ CD56+ TTF1+ SYNAPTOPHYSIN+

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

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

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

  7. 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

  8. Sundstrom et al. JCO 2002

  9. 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

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

  11. RADIATIONJCO 1992 Warde & Payne

  12. TIMING OF RADIATIONNCIC BR-5 JCO 1993 Murray,N

  13. 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)

  14. 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

  15. ASCO 2007

  16. ASCO 2007

  17. ASCO 2007

  18. EXTENSIVE SCLCNCIC BR8 JCO 1999 MURRAY,N et al.

  19. 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

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

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

  22. SECOND LINE Rx • IMPORTANCE OF PROGRESSION FREE INTERVAL • <3mos,>6-12mos • Patient selection • MEDIAN SURVIVAL 2-3mos

  23. 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,$

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

  25. 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 SCLC SUMMARY

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

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