Early Stage NSCLC: The Role of Chemotherapy .


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Early Stage NSCLC: The Role of Chemotherapy. Eric Vallieres, MD . USA 2003. Clinical IB, IIA, IIB diseases. Resection by lobectomy or more if cardiopulmonary reserves 5-y Survival = 20-40 % Adjuvant Therapy ? Induction Therapy ?. cT2N0 RUL NSCLC. Adjuvant Radiotherapy.
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Early Stage NSCLC: The Role of Chemotherapy Eric Vallieres, MD

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USA 2003

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Clinical IB, IIA, IIB illnesses Resection by lobectomy or increasingly if cardiopulmonary stores 5-y Survival = 20-40 % Adjuvant Therapy ? Acceptance Therapy ? cT2N0 RUL NSCLC

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Adjuvant Radiotherapy

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Adjuvant Radiotherapy N2 seemed to pick up 1 month in survival...

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MRC LCWP Stephens et al, Br J Cancer 1996

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Adjuvant Radiotherapy No change in survival Improved loco-provincial control with squamous histology (LCSG 773) however systemic disappointments prompt passing...

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Adjuvant Chemotherapy

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Adjuvant Chemotherapy ALPI (Adjuvant Lung Project Italy) Tonato, PASCO 2002 unique 1157

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Events/Total CT 278/548 Control 288/540 HR=0.96 (0.81 - 1.13) p=0.585 Overall Survival PROBABILITY Median f/up of 63 months YEARS

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Adjuvant Chemotherapy Over the most recent 30 years, on trial, the conveyance of the expected chemotherapy has been reliably poor: LCSG 801 (CAP * 4) = 53% JCOG 8601 (C Vd *3) = 68% ALPI (MVdP * 3) = 70%

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Clinical IB, IIA, IIB sicknesses Resection by lobectomy or increasingly if cardiopulmonary stores 5-y Survival = 20-40 % Adjuvant Therapy = NO Induction Therapy ? Check not accessible cT2N0 RUL NSCLC

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3 cycles carboplatin/paclitaxel re-imaged 4 weeks after the fact Pre Post Scans not accessible

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Induction Chemotherapy The BLOT Phase II Study Pisters K et al., J Thor CV Surg 2000; 119:429-439

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The BLOT Study 94 patients 98% finished enlistment chemo as arranged Clinical major RR: 53/90 ( 58.9%) Pisters K et al., J Thor CV Surg 2000; 119;429

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The BLOT Study Progression amid acceptance: 3/98 ( 3%) Pisters K et al., J Thor CV Surg 2000; 119;429

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The BLOT Study 86/94 were investigated 77/94 had a R0 resection ( 82%) One postoperative demise Operative horribleness similar to verifiable arrangement of Surgery alone Pisters K et al., J Thor CV Surg 2000; 119;429

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The BLOT Study Induction carboplatin/paclitaxel chemotherapy is protected and possible preceding resection of clinical early NSCLC Pisters K et al., J Thor CV Surg 2000; 119:429-439

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Induction Chemotherapy The Depierre Phase III Study Adjuvant RT for pT3 and pN2 Depierre et al., Proc ASCO 1999, unique 1792

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The Depierre Study OP MIP>OP Median survival (months) 26 p=0.11 36 Survival @ 1 y (%) 73 NS 77 @ 2y (%) 52 NS 59 @ 3y (%) 41 NS 49 Operative mortality 4.5% NS 7.8% Depierre et al., J Clin Oncol 2001; 20: 247-53

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Overall Survival 100 _ 80 _ PCT PRS _ Reference date : Nov 1, 2000 60 _ 40 _ 20 p = 0.15 _ Patients at hazard | 0 1 2 3 4 5 6 Years PCT arm 179 138 105 87 64 33 20 PRS arm 176 129 92 67 51 32 21

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Induction chemotherapy Perioperative entanglements ? Vanderbilt Historical correlation Induction PC Surgery alone N 34 67 Stages 2.52 <0.001 1.55 age, PFT, comorbid. = Life Threat. Comp. (%) 27% 0.0036 6% Reintubation 17.6% 0.0093 3% Tracheostomy 12% 0.0042 - Mortality 5.6% 0.045 - Roberts et al., Ann Thorac Surg 2001; 72: 885-8

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The Depierre Study 30 day agent mortality MIP> S n=179 7.8% S n=176 4.5% NS Breton JP et al., Proc ASCO 2001, unique 1239

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The Depierre Study 30 day agent dismalness MIP> S 39 in 33 pts S 27 in 25 pts NS Breton JP et al., Proc ASCO 2001, conceptual 1239

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The Depierre Study BPF/empyemas MIP> S 10* ( 8 early + 2 late) S 5 NS * 8/10 in N2 pts, 9/10 after pneumonectomy Breton JP et al., Proc ASCO 2001, theoretical 1239

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The Depierre Study Pulmonary contaminations MIP> S 10 S 11 NS Breton JP et al., Proc ASCO 2001, dynamic 1239

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Does acceptance chemotherapy ( without radiation ) truly increment the horribleness and mortality of lung resection ?

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Randomized Data Stage III Experience

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RESECTABLE N2 DISEASE Pre chemotherapy Post chemotherapy Scans not accessible

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Induction Chemotherapy The Roth Phase III Study (MDACC) Roth J NCI May 1994

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Induction Chemotherapy The Rosell Phase III Study Adjuvant mediastinal RTx 50 Gy Rosell NEJM Jan 1994

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Operative dangers after acceptance chemotherapy Phase III information OPERATIVE MORTALITY Pass 1992 CS(EP)>S> RT (n=13) 0% S>RT (n=14) 0% Rosell 1994 CS(MIP)>S > RT (n=30) 2/30 6.67% S > RT (n=30) 2/30 6.67% [ each of the 4 passings (2+2) were respiratory ] Roth 1994 CS(CyEP)>S (n=28) 0* S alone (n=32) 6 * had 3 treatment related passings Pass, Ann Thor Surg 1992; Rosell, NEJM 1994; Roth, J NCI 1994

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Retrospective Data

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Operative dangers after enlistment chemotherapy MDACC Aug 1996 to Apr 1999 335 back to back "lobectomies or more" for NSCLC 76 after enlistment chemotherapy 259 surgery alone Prospective information gathering of peri-agent occasions Siegenthaler et al., Ann Thor Surg 71:1105, 2001

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Operative dangers after enlistment chemotherapy MDACC (- ed) Induction chemotherapy: carboplatin/paclitaxel in 93% of pts Siegenthaler et al., Ann Thor Surg 71:1105, 2001

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Operative dangers after acceptance chemotherapy Siegenthaler et al., Ann Thor Surg 71:1105, 2001

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Operative dangers after acceptance chemotherapy MDACC (- ed) Stage particular examination : no distinction in dismalness of CS versus S alone Multivariate investigation: just CAD and pneumonectomy were free hazard variables for a noteworthy postoperative occasion. Siegenthaler et al., Ann Thor Surg 71:1105, 2001

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Operative dangers after enlistment chemotherapy MSKCC Jan 1993 to Dec 1999 412 aspiratory resections after acceptance treatment ( ages ran 25-82) Preop chemotherapy: carboplatin/paclitaxel 32% MVP 38% Preop radiotherapy too : 18% Martin J et al., Ann Thorac Surg 2001; 72: 1149-54

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Operative dangers after enlistment chemotherapy MSKCC (- ed) 297 lobectomies ( 9 sleeves, 26 bilobectomies ) 97 pneumonectomies ( 20%) 18 lesser resections, 58 O&C 22% were amplified resections Martin J et al., Ann Thorac Surg 2001; 72: 1149-54

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Operative dangers after acceptance chemotherapy MSKCC (- ed) Operative mortality Overall 3.8% Lobectomy 2.4% Left Pneumonectomy 0% Right Pneumonectomy 23.9% Multivariate investigation: right pneumonectomy was the main indicator of mortality Martin J et al., Ann Thorac Surg 2001; 72: 1149-54

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Operative dangers after acceptance chemotherapy MSKCC (conclusion) Major bleakness 26.6% , fundamentally respiratory Multivariate examination : Increased agent blood misfortune, low FEV1 and right pneumonectomy were the main autonomous indicators of post-agent horribleness The sort of enlistment regimen was not a hazard calculate. Martin J et al., Ann Thorac Surg 2001; 72: 1149-54

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Operative dangers after acceptance chemotherapy Does enlistment chemotherapy without radiationtherapy truly increment the dreariness and mortality of lung resection ? Likely not… but rather the vast majority of the information distributed so far is either review or potentially contrasting with authentic controls ...

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Induction Therapy ( pre-agent ) Ongoing Studies

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Early Stage Disease Phase III Trial INT S 9900 cT2N0, T1N1, T2N1, T3N0, T3N1 Resection Induction carboplatin/paclitaxel 3 cycles Resection Activated 11.99 Accrual objective = 600 1/24/03 = 279

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Phase III Trial INT S 9900 "Child of BLOT" " BLOT or KNOT" Through SWOG, NCCTG, ECOG, RTOG, ACOSOG, NCIC and the CTSU.

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Early Stage Disease NATCH* ( Neoadjuvant/Adjuvant Taxol Carboplatin Hope) Activated 4.00 Accrual objective = 624 * Switzerland, Spain, Germany, Portugal, Sweden

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Early Stage Disease ChEST (Chemotherapy for Early Stage Tumor) cT2N0, T1N1, T2N1, T3N0, T3N1 Resection Induction gemcitabine/cddp 3 cycles Resection Italy Accrual objective = 606-712

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Early Stage Disease MRC Lu-22 cT1N0, T2N0, T1N1, T2N1, T3N0, T3N1 Resection Induction chemotherapy* 3 cycles, Q 3weeks UK + EORTC ( 6/02) Activated Jan 1998 Accrual objective = 450 April 2002 = 239 Resection *MVP, MIP, Cis-Vinorelbine, Cis-Gem

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Will acceptance chemotherapy turn into the standard of watch over our patients with early stage illness ? Just by finishing the continuous clinical trials in an auspicious manner, will we have the capacity to answer this essential question.

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