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 ?