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Should chemotherapy be performed in elderly patients?

Should chemotherapy be performed in elderly patients?. No. Tuncay Göksel Ege University Dept. of Pulmonary Medicine. Subject of the debate. The role of chemotherapy in SCLC is clear, so it is not subject today The subject is NSCLC

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Should chemotherapy be performed in elderly patients?

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  1. Should chemotherapy be performed in elderly patients? No Tuncay Göksel Ege University Dept.of Pulmonary Medicine

  2. Subject of the debate • The role of chemotherapy in SCLC is clear, so it is not subject today • The subject is NSCLC • The debate will be done about the role of chemotherapy in elderly patients with advanced stage NSCLC

  3. American College of Chest PhysiciansChest 2007;132;277-289 • In patients who have stage IV NSCLC and are elderly (> 70 to 79 years old), single-agent chemotherapy is recommended for most. Grade of recommendation, 1A • However, in patients who have stage IV NSCLC, are elderly (> 70 to 79 years old), havegood PS, and lack significant comorbidities, two-drug combination chemotherapy is recommendedas an option. Grade of recommendation, 1B • In patients who have stage IV NSCLC and are > 80 years old, the benefit of chemotherapy is unclear and should be decided on the basis of individual circumstances. Grade of recommendation, 2C

  4. American Society of Clinical OncologyJ Clin Oncol 2009; 27:6251-6266 • Recommendation A4: The evidence does not support the selection of a specific first-line chemotherapy drug or combination based on age alone. • 2003 recommendation. For elderly patients or patients with anECOG/Zubrod PS of 2,available data support the use of singleagentchemotherapy. • In summary, clinical trial data since the 2003 update reinforce therecommendation that age alone should not be used to select chemotherapyfor patients with stage IV NSCLC. Older patients may experiencemore toxicity from cytotoxic chemotherapy than youngerpatients but may garner an equal amount of benefit.

  5. In elderly patients the recommended first-line chemotherapy is a single agent, themost extensively studied being vinorelbine and gemcitabine. European Respiratory Monograph2009; 44, 271–83

  6. National Comprehensive Cancer Network(NCCN 2009) • Single agent therapy or platinum-based combinations are reasonable alternative in PS 2 patients or the elderly

  7. “Erderly” age?65? or 70? • In epidemiological studies  >65 years J Clin Oncol 2001; 19: 1064-70 • In most clinical trials >70 years Lung Cancer 2004; 46: 61–76

  8. What is the problem in age? • Aging is inextricably associated with physiologic changes in functional status, organ function, and drug pharmacokinetics. • Aging is associated with decreases in marrow reserve, drug clearance, and lean body mass. • Furthermore, concomitant comorbidities that affect functional status, general health, and tumor symptoms are frequently present in this patient population. Gridelli, J Clin Oncol 2007; 25:1898-907  So we expect more toxicities in elderly patients during treatment

  9. Platin-based chemotherapy in elderly patients • More myelotoxicity • Greater risk of chemotherapy-related death Kubota et al:CancerChemother Pharmacol 1997; 40:469-74 Langer et al:J Natl Cancer Inst 2002; 94:173-81

  10. Elderly patients in clinical trials • Elderly patientsare under-represented in almost all clinical cancer research (also lung cancer) • In current practice, the elderly are oftenexcluded from participation in clinical trials andreceive untested or inadequate treatment based on the long-held Hutchins et al:N Engl J Med 1999; 341:2061-7 Lewis et al:J Clin Oncol 2003; 21:1383-9 Yee et al: J Clin Oncol 2003; 21:1618-23 Gridelli et al: Clin Oncol 2007; 25:1898-907

  11. The ratio of elderly and chemotherapy • Approximately two thirds of patients with NSCLC are 65 years old, and approximately 40% are 70years old SEER Data, Semin Surg Oncol 1994; 10:21–30 • The rate of patients who are 70 years old is closer to 50% SEER Data, J Clin Oncol 2004; 22:4971–8 • Elderly patients are generally underrepresented on clinical trials; participation of elderly patients with advanced disease in national clinical trials has ranged 15% -29%. The highly selected population is not representative of the general population • A much lower rate of chemotherapy use than expected for the overall population in elderly patients • More comorbidities • A higher rate of functional compromise

  12. January 1, 1994, and December 31, 1999, SEER Data • 14,875 patients; 49.8% stage III and 50.2% stage IV

  13. SEER Study, Ramsey et al. J Clin Oncol; 22:4971-4978 2004 Co-m 44% CT 33%

  14. SEER Study, Ramsey et al. J Clin Oncol; 22:4971-4978 2004

  15. SEER Study, Ramsey et al. J Clin Oncol; 22:4971-4978 2004 Median survival No chemotherapy 5 months (Poor performans patients) Chemotherapy 8 months (P .01)

  16. SEER Study, Ramsey et al. J Clin Oncol; 22:4971-4978 2004

  17. Phase III trials of advanced NSCLC in elderly patients

  18. The Elderly Lung CancerVinorelbine Italian Study Group(ELVIS) çalışmasıJ Natl Cancer Inst 1999;91:66–72 • 70 years of age or older, • Stage IV or IIIB NSCLC • Performance status of 0–2  Vinorelbin vs BSC

  19. ELVIS, J Natl Cancer Inst 1999;91:66–72

  20. ELVIS J Natl Cancer Inst 1999;91:66–72

  21. ELVIS, J Natl Cancer Inst 1999;91:66–72 • Median survival • Vinorelbinearm: 28 week • Control arm: 21 week (p=0.03). ONLY: 7 weeks • The objective response rate: 19.7%

  22. ELVIS, J Natl Cancer Inst 1999;91:66–72 Toxicity • 93% of patients were assessed fortoxicity. (Grade1-4) • Treatment was stopped in five patients because of severe toxic events

  23. De Marinis et al, lonidamine vs vindesine vs lonidamine+vindesine vs BSC in elderly NSCLCTumori. 1999 May-Jun;85(3):177-82. • Stage IV: 40% • Stage III: 60% • Early discontination • 8.7%progressed early • 9.5% died early • 9.4% refused treatment continuation because of poor compliance

  24. De Marinis et al, lonidamine vs vindesine vs lonidamine+vindesine vs BSC in elderly NSCLCTumori. 1999 May-Jun;85(3):177-82. • Overall response • lonidamine: 1/30 • lonidamine + vindesine arm: 2/33 • Toxicity (all treated patients) • Leukopenia (grade 1-3): 30% • Myalgia: 70% • Fatigue 55-83% • Testicular pain: 40% • The overall median survival was 170 days, with no significant impact on survival of either lonidamine or vindesine.

  25. MILES study,J Natl Cancer Inst 2003;95:362–72] • A randomized phaseIII trial in elderly patients with advanced NSCLC (older 70 years) • Vinorelbine • Gemcitabine • Vinorelbineplus gemcitabine

  26. MILES study,J Natl Cancer Inst 2003;95:362–72]

  27. MILES study,J Natl Cancer Inst 2003;95:362–72] No chemotherapy (poor performans patients): 5 months SEER Study, Ramsey et al. J Clin Oncol; 22:4971-4978 2004

  28. MILES study,J Natl Cancer Inst 2003;95:362–72]

  29. MILES study,J Natl Cancer Inst 2003;95:362–72]

  30. Frasci et al, Gemcitabine Plus Vinorelbine Versus Vinorelbine Alone in Elderly PatientsJ Clin Oncol 2000 18:2529-2536

  31. Frasci et al, Gemcitabine Plus Vinorelbine Versus Vinorelbine Alone in Elderly PatientsJ Clin Oncol 2000 18:2529-2536

  32. Frasci et al, Gemcitabine Plus Vinorelbine Versus Vinorelbine Alone in Elderly PatientsJ Clin Oncol 2000 18:2529-2536 No chemotherapy (poor performans patients): 5 months SEER Study, Ramsey et al. J Clin Oncol; 22:4971-4978 2004

  33. Frasci et al, Gemcitabine Plus Vinorelbine Versus Vinorelbine Alone in Elderly PatientsJ Clin Oncol 2000 18:2529-2536

  34. Frasci et al, Gemcitabine Plus Vinorelbine Versus Vinorelbine Alone in Elderly PatientsJ Clin Oncol 2000 18:2529-2536

  35. Frasci et al, Gemcitabine Plus Vinorelbine Versus Vinorelbine Alone in Elderly PatientsJ Clin Oncol 2000 18:2529-2536

  36. Takeda et al, Phase III study of docetaxel versus vinorelbine for elderly patients with NSCLCJ Clin Oncol 2005; 23 (16S): 623s (Abstr 7009). • Single-agent docetaxel vs vinorelbine in 180 elderly patients with good PS • Objective response rate • Docetaxel: 22.7% • Vinorelbine: 9.9% (p = 0.019) • Survival • Docetaxel: 13.9 months • Vinorelbine: 9.9 months (p = 0.038) • Major toxicity: grade 3–4 neutropenia • Docetaxel: 83.0% • Vinorelbine: 69.2% (p = 0.031)

  37. Retrospective Subset Analyses of Elderly Patients in Randomized Trials of Platinum-based ChemotherapyCHEST 2007; 132:277S–289S

  38. Phase II single-agent chemotherapy studies for elderly patients with NSCLC CHEST 2005; 128:947–957

  39. Phase II Trials of Non–Platinum-Based Combination ChemotherapyCHEST 2005; 128:947–957

  40. Phase II Trials of platin and 3. generation chemotherapy agent CHEST 2005; 128:947–957

  41. Summary • There is no enough randomized phase III trial, so the available data is not enough • To make a decision according to phase II or retrospective analysis can be wrong • The rate of toxicity is high • The rate of continuing of treatment is low • It is not performed routinely • It can be made a decision based on patient

  42. Summary • If it will be performed • Patients with good performance (0-1) • Patients without severe underlying disease • Third generation single-agent chemotherapy should be preferred

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