1 / 28

The Role of Neoadjuvant Chemotherapy in Nonsmall Cell Lung Cancer

The Role of Neoadjuvant Chemotherapy in Nonsmall Cell Lung Cancer. Nil Molinas Mandel Istanbul University Cerrahpaşa Medical Faculty Medical Oncology Department. The use of systemic therapy before definitive local regional therapy is generally referred to as induction or neoadjuvant therapy.

carol
Télécharger la présentation

The Role of Neoadjuvant Chemotherapy in Nonsmall Cell Lung Cancer

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. The Role of Neoadjuvant Chemotherapy in Nonsmall Cell Lung Cancer Nil Molinas Mandel Istanbul University Cerrahpaşa Medical Faculty Medical Oncology Department

  2. The use of systemic therapy before definitive local regional therapy is generally referred to as induction or neoadjuvant therapy

  3. Rationale • 55% of patients with lung cancer have distant metastasis at diagnosis. • 25% have regional node involvement. • 15% have localized disease.

  4. Rationale • At the time of the diagnosis, fewer than 25% of all pts are candidate for surgery • Cure after resection is higly dependent of stage and nodal status of disease • After resection 5yr survival Without nodal metastasis 70% Hilar metastasis 50% Mediastinal metastasis 5%

  5. 5 Year Survival Rate Stage Grouping 5 Year Survival IA T1N0 75% IB T2N0 55% IIA T1N1 50% IIB T2N1 40% T3N0 IIIA T1-3N2 15% T3N1 35% IIIB T1-3N3 5-10% T4anyN 5-10%

  6. Surgery alone is not enough to cure the majority of patients even with resectable disease Need of multimodality approach to the treatment...

  7. ADVANTAGES NEOADJUVANT THERAPY • Early eradication of micrometastasis • Cytoreduction of local disease • Improvement in resection rates • In vivo test of chemosensitivity

  8. DISADVANTAGES NEOADJUVANT THERAPY • Increased morbidity and mortality • Ineffective induction regimen • Progression of resectable disease

  9. Evidence 5 meta-analyses, 20 phase III trials, 100 phase II trials • Stage I and II • Stage IIIA • Stage IIIB

  10. Stage I and Stage II • Bimodality Lung Oncology Team (BLOT) Trial (updated in ASCO 2003 meeting) MSK and MD Anderson Phase II, 134 pts IB-IIIA (N0/N1) were included, 2-3 preop paclitaxel+carbo (-/+ postop)were given. Perop mortality was %1 with acceptable toxicity. Preop RR: %53 3yr survival was 61%, 5yr survival is 42%

  11. Stage I and Stage II • SWOG 9900 phase III trial, 3cycles of CT (T2N0, T1-2N1, %30 T3N0-1) • Preop RR: %40, mSV preop CT arm 47 mo, surgery alone 40 mo (HR: 0.84, p=0.32) • The trial closed earlier because investigators considered that having surgery alone arm could no longer be considered ethical.

  12. Stage I and Stage II • NATCH Trial, since 2000, NCSLC Stage I, II (T3N0-1) 3-arm randomized trial is comparing: Surgery alone 3 cycles of neoadjuvant CT with paclitaxel/carbo 3 cycles of adjuvant CT with paclitaxel/carbo

  13. 5-Year Results of French randomized study comparing preop CT followed by surgery and primary surgery in resectable Stage I, II, IIIA NSCLC • Deppierre A et al, World conference on Lung Cancer 2003 • Only phase III trial in IB, II, IIIA pts • 355 pts were randomized to surgery and primary CT+S Arm 1yr % 3yr % 5yr % Preop CT 76,5 52 41,3 Surgery 73,3 41,5 31,6 Difference 3,2 10,5 9,7 P 0,48 0,04 0,06

  14. Stage IIIA • Stage IIIA (N2) around 25 phase II trial • 1000 pts were included • Average response rate 62% (38-86) • 55% pts underwent thoracotomy • 49,1% were successfuly resected • Pathological complete response rates were 10-20% • Median survival time was 16,5 mo • 5yr survival was 30% in responsive pts, 50% in CR

  15. Phase III Trials in Resectable NSCLC Study Stage CT RT pts 2-3yr p NCI IIIA(N2)Bx EP(+/+) post op control 28 46/21% 0,12 Japan IIIA, IIIB c VdP(+/-) concurrent 83 40/37% NS MDA IIIA(N2) c CEP(+/+) post op 60 56/15% 0,05 Spain IIIA (N2) c PIM(+/-) post op 60 0/30% 0,05 FTCG IB, II, IIIA c MIP(+/+) post op T3/N2 355 41/52% 0,09 (French Thoracic Cooperative Group)

  16. Criticism • Pts were staged clinically, not pathologically • T3N0 pts were included • Small number of patients • Prognostic factors like k-ras were not balanced

  17. Radiotherapy as a part of induction therapy

  18. CONCURRENT INDUCTION CHEMORADIOTHERAPY TRIALS Study IIIA(N2)T4/N3 CT RT post op SWOG 8805 60% 40% EP 45Gy no resp 2XCT+RT LCSG 852 87% 13% PF 30Gy none R-Presbyterian 73% 6% PF/PEF 40Gy none CALGB 80% 20% PVF 30Gy 1xCT+RT Tufts 47% 53% EP 59Gy PE or Carbo + T

  19. CONCURRENT INDUCTION CHEMORADIOTHERAPY TRIALS Study Pts RR% Res R% Op mortality Surv SWOG 8805 126 59 71 8 15 mo LCSG 852 85 56 52 7 13 R-Prebs. 85 92 71 4 22 CALGB 41 64 61 15 16 Tufts 55 69 76 5 20

  20. NEW AGENTS • Docetaxel + platinum In stage III, 3 phase II trials, In stage III one phase III trials (single agent) RR 68-82 % Complete resection is possible in 69-79% of pts • Gemcitabine + platinum In stage III, 4 phase II trials RR 52-62%, CR 4,7-15% Downstaging 41-77%

  21. What is the role of surgery after induction therapy ?

  22. Intergroup trial 0139 ( RTOG 93-09), ASCO 2003 • Phase III comparison of concurrent CT+RT and CT+RT followed by surgical resection for stage IIIA (pN2) • Tested the role of surgery after induction with chemoradiotherapy for PFS and OS • T1-3N2M0 pts were included ( resection is technically feasible) • PE X2 + RT 45Gy  Surgery vs PE X4 + RT 61Gy • Compliance was good for induction therapy • CT+RT+ surgery arm had better PFS (14 vs10,7m p0,02) • 3 yr overall survival was 38% vs 33%

  23. Nodal stage after induction therapy in Stage IIIA • Retrospective analysis of 103 pts with cisplatin based neoadjuvant CT and surgery • Pts with N2+ disease whose nodal disease was eradicated after neoadjuvant therapy and surgery had significantly improved cancer free survival • Pts, whose nodal disease was not downstaged after neoadjuvant therapy did not benefit from surgical resection Bueno R et al , Ann Thorac Surg, 2000

  24. Stage IIIB • Limited number of phase II trials, no phase III • Pts with T4N0-1 (satellite nodule within the primary tumor lobe) have 20% 5yr survival with surgery alone • Pts with T4N0-1( main carinal involvement) have 15% 5yr survival with surgery • In 51 pts with stage IIIB (excluding pts with SVCS) SWOG study showed 80% resectability rate, and 24% 3 year survival with concurrent chemo-radiotherapy

  25. Treatment Related Morbidity and Mortality in Combined Modality Induction Trials • All combined modality induction programs were tested in “fittest” pts, who were fully ambulatory and had good general medical condition • It may be harmful to offer this type of therapy to pts who have a poor performance status and major co-morbidities

  26. Toxicity • During Induction: myelosuppression, emesis, mucositis, esophagitis ( RT) • During the 30-Day Postoperative Time: Pneumonitis, ARDS, Bronchopleural fistules • After Postoperative Time: Toxicities of additional therapies Post-treatment constitutional syndrome

  27. Future Challenges • Is there a role of prophylactic brain metastasisi in stage III patients? • Trials analyzing customized neoadjuvant chemotherapy is warranted. Pts with lowest BRCA1, RRM1 mRNA levels after chemotherapy have better outcome. • Neoadj CT with new drugs (Premetrexed/CDDDP)? • The role of biological agents? Erlotinib, gefitinib, bevacizumab (CT+ biological agents )

  28. Conclussion • In spite of these promising results with neaoadjuvant therapy, surgery remains the mainstay of treatment of lung cancer • In stage IIIA trials suggest that induction chemotherapy (with or without RT) improves survival, particulary in pts with significant downstaging of the disease • In stage I, II, and IIIB use of the neoadjuvant therapy is still not a standard approach

More Related