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  SPECTRUM CARCINOID-ATYPICAL CARCINOID-SMALL CELL  IHC KERATIN+ CD56+ TTF1+ SYNAPTOPHYSIN+

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

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

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

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

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

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

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

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

TIMING OF RADIATION NCIC BR-5 JCO 1993 Murray,N EP/CAV wk3 4000/15 EP/CAV wk /15 Median Survival(mos) yr Survival(%) yr Survival(%) Esophagitis (%)

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)

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

ASCO 2007

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

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

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

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

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

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,$

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

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

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