- The document discusses the role of chemotherapy in early stage non-small cell lung cancer (NSCLC), including adjuvant and induction chemotherapy.
- Several studies on induction chemotherapy found it to be safe and feasible prior to surgery, with high rates of tumor response and similar postoperative complications compared to surgery alone. However, larger phase III studies are still ongoing.
- The optimal use of chemotherapy, whether adjuvant or induction, in early stage NSCLC remains unclear and requires completion of current clinical trials.
7. Adjuvant Radiotherapy No improvement in survival Improved loco-regional control with squamous histology (LCSG 773) but systemic failures lead to death...
15. The BLOT Study 94 patients 98% completed induction chemo as planned Clinical major RR: 53/90 ( 58.9%) Pisters K et al., J Thor CV Surg 2000; 119;429
16. The BLOT Study Progression during induction: 3/98 ( 3%) Pisters K et al., J Thor CV Surg 2000; 119;429
17. The BLOT Study 86/94 were explored 77/ 94 had a R0 resection ( 82%) One postoperative death Operative morbidity comparable to historical series of Surgery alone Pisters K et al., J Thor CV Surg 2000; 119;429
18. The BLOT Study Induction carboplatin/ paclitaxel chemotherapy is safe and feasible prior to resection of clinical early NSCLC Pisters K et al., J Thor CV Surg 2000; 119:429-439
19. Induction Chemotherapy The Depierre Phase III Study Depierre et al., Proc ASCO 1999, abstract 1792 Adjuvant RT for pT3 and pN2
20. 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% The Depierre Study Depierre et al., J Clin Oncol 2001; 20: 247-53
21. Overall Survival 1 2 5 3 Years 4 100 80 60 40 20 p = 0.15 PCT PRS | | | | | _ _ _ _ _ _ _ _ _ _ 6 | Reference date : Nov 1, 2000 PCT arm 179 138 105 87 64 33 20 PRS arm 176 129 92 67 51 32 21 0 Patients at risk
22. Vanderbilt Historical comparison 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 -- Induction chemotherapy Perioperative complications ? Roberts et al., Ann Thorac Surg 2001; 72: 885-8
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27. Does induction chemotherapy ( without radiation ) really increase the morbidity and mortality of lung resection ?
35. Operative risks after induction chemotherapy MDACC (-ed) Induction chemotherapy: carboplatin/ paclitaxel in 93% of pts Siegenthaler et al., Ann Thor Surg 71:1105, 2001
36. Operative risks after induction chemotherapy Siegenthaler et al., Ann Thor Surg 71:1105, 2001
37. Operative risks after induction chemotherapy MDACC (-ed) Stage specific analysis : no difference in morbidity of CS vs. S alone Multivariate analysis: only CAD and pneumonectomy were independent risk factors for a major postoperative event. Siegenthaler et al., Ann Thor Surg 71:1105, 2001
38. Operative risks after induction chemotherapy MSKCC Jan 1993 to Dec 1999 412 pulmonary resections after induction therapy ( ages ranged 25-82) Preop chemotherapy: carboplatin/ paclitaxel 32% MVP 38% Preop radiotherapy as well : 18% Martin J et al., Ann Thorac Surg 2001; 72: 1149-54
39. Operative risks after induction chemotherapy MSKCC (-ed) 297 lobectomies ( 9 sleeves, 26 bilobectomies ) 97 pneumonectomies ( 20%) 18 lesser resections, 58 O&C 22% were extended resections Martin J et al., Ann Thorac Surg 2001; 72: 1149-54
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41. Operative risks after induction chemotherapy MSKCC (conclusion) Major morbidity 26.6% , mainly respiratory Multivariate analysis : Increased operative blood loss, low FEV1 and right pneumonectomy were the only independent predictors of post-operative morbidity The type of induction regimen was not a risk factor. Martin J et al., Ann Thorac Surg 2001; 72: 1149-54
47. Early Stage Disease ChEST (Chemotherapy for Early Stage Tumor) cT2N0, T1N1, T2N1, T3N0, T3N1 Resection Induction gemcitabine/ cddp 3 cycles Resection Italy Accrual goal = 606-712
48. Early Stage Disease MRC Lu-22 cT1N0, T2N0, T1N1, T2N1, T3N0, T3N1 Resection Induction chemotherapy* 3 cycles, Q 3weeks Resection UK + EORTC ( 6/02) Activated Jan 1998 Accrual goal = 450 April 2002 = 239 *MVP, MIP, Cis-Vinorelbine, Cis-Gem
49. Will induction chemotherapy become the standard of care for our patients with early stage disease ? Only by completing the ongoing clinical trials in a timely fashion, will we be able to answer this very important question.