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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 - PowerPoint PPT Presentation
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SMALL CELL LUNG CANCER 2007
BP HIGGINS MD FRCPCCFPRCC
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
REGIMEN EP5CYCLES
CEV5 CYCLES
MEDIANSURVIVAL(mos)
14.5 9.7
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
RADIATIONJCO 1992 Warde & Payne
LOCAL RELAPSE2 YEARS(%)
RADS40
NO RADS65
OVERALL SURVIVAL2 YEARS(%)
22 16
Rx MORTALITY(%)
2 1
TIMING OF RADIATIONNCIC BR-5 JCO 1993 Murray,N
EP/CAV wk34000/15
EP/CAV wk154000/15
Median Survival(mos)
21 16
2 yrSurvival(%)
40 33
5 yrSurvival(%)
20 11
Esophagitis(%)
15 7.5
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
ASCO 2007
ASCO 2007
EXTENSIVE SCLCNCIC BR8 JCO 1999 MURRAY,N et al.
GOLDIE/COLDMANDOSE INTENSITY
CODE x 6 CAV/EP x 6
CR (%) 23 20
OVERALLSURVIVAL (y)
0.98 0.91
Rx Mortality (%)
8.2 0.9
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
Copyright © American Society of Clinical Oncology
Hanna, N. et al. J Clin Oncol; 24:2038-2043 2006
Fig 2. Overall survival
Copyright © American Society of Clinical Oncology
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
SECOND LINE Rx
IMPORTANCE OF PROGRESSION FREE INTERVAL
<3mos,>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 ?
