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Highlites in NSCLC: Combined modality treatment in stage III disease

Highlites in NSCLC: Combined modality treatment in stage III disease. Lucio Trodella Cattedra di Radioterapia Oncologica Università Campus Bio-Medico Roma. Chemoradiotherapy: Questions. Sequential Chemotherapy  Radiotherapy X X X.

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Highlites in NSCLC: Combined modality treatment in stage III disease

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  1. Highlites in NSCLC:Combined modality treatment in stage III disease Lucio Trodella Cattedra di Radioterapia Oncologica Università Campus Bio-Medico Roma

  2. Chemoradiotherapy: Questions Sequential Chemotherapy  Radiotherapy X XX Concurrent Chemoradiotherapy(x) (x) (x) Induction Chemotherapy  Concurrent Chemoradiotherapy X XX (x) (x) (x) Concurrent Chemoradiotherapy  Consolidation Chemotherapy (x) (x) (x) X XX Concurrent Chemoradiotherapy  Surgery

  3. 2004

  4. Overall survival Favours Concurrent CT+RTvs CTRT 60-66Gy once daily RTOG 9410 NPC 9501 0,86 [0,78-0,95] 711 pts Favours Sequential Rowell 2004 Cochrane Review

  5. Treatment-related toxicity Favours Sequential RTOG 9410 NPC 9501 Favours Concurrent Rowell 2004 Cochrane Review

  6. Concurrent CT-RT vs CTRTRowell, The Cochrane Meta-analysis, 2004 2004 • A 14%reduction in risk of death at 2 years with concurrent treatment (RR 0.86; 95% CI 0.78 to 0.95; p = 0.003), but at the expense of toxicity (acute esophageal toxicity)

  7. 2007

  8. 2007 Total dose 144 mg/m2 189 deatheventswereexpectedforeacharm. The studywasinterrupted at 158 accruedpatients, due todifficulties in accrual. (62 deaths–armSequential & 58 deathsarmConcurrent)

  9. Metanalisi di Rowell 2004 -ConclusioniConc. CT-RT (C)vsSequential CTRT (S) S 2y Trial N. Conc Seq RT Curran 2003* 402 37% 31% 60/30fr Zatloukal 2004* 102 34% 14% 60/30fr Fournel 2005* 205 35% 23% 66/33fr 2007 • EORTC 08972-22973 158 39% 34% 66/24fr 2004 *Citati nella metanalisi di Rowell 2004 Cochrane

  10. Combined Modality in Stage III NSCLC Meta-analyses evaluating optimal chemoRT strategy Rolland E et al. J Thor Oncol 2 (8): S309, 2007, abstract Auperin A et al. J Thor Oncol 2 (8): S310, 2007, abstract

  11. Take Home Message “Concurrent treatment is better and feasible”

  12. Studio randomizzato di fase III con Docetaxel, e cisplatino versus mitomicina, vindesina e cisplatino associati a Radioterapia nel NSCLC: OLCSG 0007 Kiura K (200 pz)

  13. Chemoradiotherapy: Questions Sequential Chemotherapy  Radiotherapy X XX Concurrent Chemoradiotherapy(x) (x) (x) Induction Chemotherapy  Concurrent Chemoradiotherapy X XX (x) (x) (x Concurrent Chemoradiotherapy  Consolidation Chemotherapy (x) (x) (x) X XX Concurrent Chemoradiotherapy  Surgery

  14. Vokes ASCO 04 2007

  15. CALGB 39801- Vokes ASCO ‘04 2007

  16. CALGB 39801- Vokes ASCO ‘04 p=NS Conclusion “Our results do not support the use of induction chemotherapy followed by CT/RT as evidence based standard of care for patients with unresectable stage III NSCLC”

  17. Induction chemotherapy followed by concurrent radiochemotherapy (CCRT) versus CCRT alone for locally advanced unresectable stage III NSCLC: Randomized phase III trial Min Kyoung Kim, Woo-Sung Kim Daegu, Korea Seul 2007

  18. Study Design Locally advanced unresectable stage III NSCLC Randomization Arm A Standard CCRT Arm B IC CCRT Gemcitabine 1000 mg/mq IV/1 hr d1,d8 Cisplatin 70 mg/mq IV/1hr d1 q21 for a total of 2 cycles Paclitaxel 50 mg/mq IV/1hr/week Cispaltin 20 mg/mq IV/1hr/week For a total of 6 cycles With RT total 66 Gy/30 fraction Paclitaxel 50 mg/mq IV/1hr/week and Cispaltin 20 mg/mq IV/1hr/week for a total of 6 cycles with RT total 66 Gy/30 fraction

  19. Survival

  20. Take Home Message Induction chemotherapy does not improves OS and PFS

  21. In Bulky desease?

  22. RTCT in locally advanced NSCLC Taxanes and concurrent Radiotherapy

  23. RTCT in locally advanced NSCLC Gemcitabine or Vinorelbine and concurrent RT

  24. Chemioterapia di induzione con docetaxel e cisplatino seguita da radiochemioterapia con docetaxel settimanale in NSCLC stadio III: Galician Lung Cancer group G Huidobro, M Amenedo 71 pazienti inoperabili (66 valutabili) 70% IIIB Docetaxel 75 mg/mq e Cisplatino 40 mg/mq giorni 1,2 q 21 seguito da RT 60-66 Gy con fx 1.8 Gy/die con docetaxel 30 mg/mq ogni 2 settimane Risposta RECIST alla Chemio 1 CR e 39 PR ( RR 61%), 28% SD, 8,9 % PD ASCO 2008, Abstract 7561

  25. Induzione con gemcitabina, docetaxel e cisplatino più chemioterapia concomitante a radioterapia toracica nel NSCLC stadio III S. De Santis, F. De Marinis RR 60% CHIR 44% pN0 58% Boost RT-CT 33%

  26. Take Home Message “Induction chemotherapy does not improves OS and PFS but… …in selected Bulky Disease patientsINDUCTIONCHEMOTHERAPY can be usefull reducing Radiotherapy Target Volume”

  27. Chemoradiotherapy: Questions Sequential Chemotherapy  Radiotherapy X XX Concurrent Chemoradiotherapy(x) (x) (x) Induction Chemotherapy  Concurrent Chemoradiotherapy X XX (x) (x) (x Concurrent Chemoradiotherapy  Consolidation Chemotherapy (x) (x) (x) X XX Concurrent Chemoradiotherapy  Surgery

  28. SWOG 9504, phase II trial Consolidation docetaxel after concurrent chemoradiotherapy in stage IIIB non-small cell lung cancer: phase II trial Southwest Oncology Group Study 9504 Gandara, J Clin Oncol 21:2004-10, 2003

  29. SWOG 9504 Phase II Trialof Consolidation Docetaxel Median follow-up: 71 mo 83 Patients Percentage of patients Stage IIIB Cisplatin/VP16XRT Docetaxel75 mg/m2 cycle 1 then100 mg/m2 cycles 2-3 54 MST: 26 months 37 29 29 2-y 3-y 4-y 5-y Gandara et al. Clin Lung Cancer. 2006;8:116-21.

  30. Chemo-radiotherapy of NSCLC Conclusion The core regimen of PE\TRT followed by docetaxel exhibits favorable survival and can be considered a standard treatment option for patients with unresectable Stage III NSCLC Kelly K, ASCO ‘05

  31. Secondary endpoints: PFS, toxicity HOG LUN 01-24 Phase III Study Design ChemoRT Cisplatin 50 mg/m2 IV d 1,8,29,36Etoposide 50 mg/m2 IV d 1-5 & 29-33Concurrent RT 59.4 Gy (1.8 Gy/fr) 203 patients • Stratificationat randomization • PS 0-1 vs 2 • IIIA vs IIIB • CR vs non-CR • Inclusion at baseline • Unresectable stage IIIA or IIIB NSCLC • ECOG PS 0-1 at study entry (+PS2 at random) • FEV-1 > 1 liter at study entry 147 patients 73 patients 74 patients Observation Taxotere75 mg/m2 q 3 wk  3 Primary endpoint: OS Hanna et al. WCLC 2007

  32. HOG LUN 01-24: OS (ITT)Randomized Patients (n=147) 100% 75% P-value: 0.940 50% Percent of patients surviving 25% 0% 0 10 20 30 40 50 60 Months Since Registration Hanna et al. WCLC 2007

  33. Grade 3/4 Non-Hematological Toxicities Hanna et al. WCLC 2007

  34. Take Home Message Consolidation chemotherapy does not improves OS

  35. Chemoradiotherapy: Questions Sequential Chemotherapy  Radiotherapy X XX Concurrent Chemoradiotherapy(x) (x) (x) Induction Chemotherapy  Concurrent Chemoradiotherapy X XX (x) (x) (x Concurrent Chemoradiotherapy  Consolidation Chemotherapy (x) (x) (x) X XX Concurrent Chemoradiotherapy  Surgery

  36. T Station 4R Station 7 NEOADIUVANT RT RADICAL RT IIIAIIIB

  37. Has the surgery any role? Marginally resectable disease Surgery The 5-year SVV tends to be less than 5% Martini N,. Preoperativechemotherapy for stage IIIa (N2) lung cancer: the Sloan–Kettering experience with 136 patients. Ann Thorac Surg1993;55:1365–74.

  38. La Chemioterapia neoadiuvante 493 CT+ S 988 pts 495 S

  39. La Chemioterapia neoadiuvante

  40. La Chemioterapia neoadiuvante Dautzenberg 1990, Roth 1998, Rosell 1999, Depierre 2002, JCOG 9209 Nagai 2003, Sorensen ASCO 2006, SWOG 9900 Pisters ASCO 2007

  41. Take Home Message Induction chemotherapy is better than surgery alone

  42. Stages: IIIA: Evidences 100 80 60 40 Logrank p > 0.05 Hazard ratio = 1,06 (0.84, 1.35) 20 Surgery Radiotherapy 0 months 12 24 36 48 60 72 84 96 108 • EORTC 08941 • CtindORRandom  Surgery vs RT 2007

  43. “In NSCLC patients with N2 disease identified Preoperatively, platinum-based combination chemoradiotherapy is recommended as primary treatment”

  44. “In NSCLC patients with cN2 disease neoadiuvantchemotherapy is standard treatment”

  45. Ulteriore Opzione Terapeutica: La Radiochemioterapia

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