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E-81.Small cell lung cancer- treatment strategies in the elderly and poor performance status patients
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E-8 1. Small Cell Lung Cancer - Treatment Strategies in the Elderly and Poor Performance Status Patients N. Thatcher CRC Department
of Medical
Oncology,
Christie
Hospital
Lung cancer increases in frequency with age, 40% of patients being over 75 years. Furthermore, 90% of older patients have comorbidity [Brown et al., Thorax 1996; Extermann et al., J Clin 0~01 19981. Treatment aims should reflect the difference in patient prognosis so as not to under-treat the better prognosis patients nor over-treat those with poor prognosis. Furthermore the elderly patient is just as likely to accept treatment but tend to be more conservative in trading off toxicity with likely benefit [Yellen et al., JNCI 19941. Patient groups: Several independent factors carry an adverse prognosis in addition to extensive stage (ES) ie. poor performance status, elevated LDH, alkaline phosphatase and low sodium are the most consistent [Sagman et al., J Clin Oncol 1991; Thatcher et al., Semin Radiat Oncol 19951. Age is not an independent poor prognostic factor. Patients at high risk of dying within the first few weeks of starting chemotherapy tend to have a low PS, be more elderly and with abnormal biochemistry eg. high LDH [Lassen et al., Br J Cancer 1999; Radford et al., Eur J Cancer 19921. Chemotherapy: Given promising phase II data, single agent oral etoposide was thought to be an near ideal therapy for the poorer prognostic elderly groups. However, two large randomised trials demonstrated significantly inferior survival compared with combination iv chemotherapy with no detriment in quality of life or symptomatic relief [Thatcher et al., Lancet 1996; Souhami et al., JNCI 19971. Another randomised trial of two drugs versus four drugs in poor performance status patients also reported lower toxicity with similar survival with the etoposide vincristine doublet combination [Bleehen et al., 19961. Phase II studies have suggested that elderly or infirm LS patients can benefit from just two courses of CAV then PE chemotherapy with concurrent thoracic irradiation [Murray et al., J Clin Onco1 19981. A randomised study compared CAV with single agent carboplatin in a poor prognostic group. There was no significant survival or symptom relief difference but with a lower risk of life threatening sepsis with single agent carboplatin [White et al., Cancer 20011. Nevertheless the search for more effective agents
NHS Trust,
Wilmslow
Road,
Manchester
M20 4BX
UK
continue and oral topotecan has been specifically investigated in an elderly group [Eckardt et al., Lung Cancer 20001. Radiotherapy: For LS patients thoracic radiotherapy can be appropriate. The meta analysis revealed no difference between good and poorer PS patients. However, the survival gain was greatest for patients ~55 years of age and there was a small survival detriment in patients older than 70 years [Pignon et al., NEJM 19921. Prophylactic cranial irradiation with survival gain was not age dependent and there appeared to be no increase in neuropsychological changes in two trials [Auperin NEJM 19991. Conclusion: Elderly, impaired PS patients are underrepresented in trials and there is little data to guide clinical decisions. Further work in defining high risk groups with validation is required to help target treatment more appropriately. For the fit elderly patient standard treatment should be considered. However, for the unfit patients or elderly patients with considerable comorbidity single agent chemotherapy may be appropriate or a fewer number of courses of standard chemotherapy. The comorbidity issues and appropriate supportive care perhaps with agents such as erythropoietin should also be considered.
References 111 Auperin A, Arriagada R, Pignon J-P et al., N Engl J Med 341:476-484,1999.
PJ Eckardt
JR, Palmer MC, Fanucchi MP et al., Lung Cancer (abstr 25), ~10, 2000. M, Overcash j, Lyman GH et al., J Clin Oncol 16:1582131 Extermann 1587,1998. [41 Lassen UN, Osterlind K, Hirsch FR et al., Br J Cancer 79:515-519, 1999. [51 Medical Research Council Lung Cancer Working Party, Br J Cancer 73:406413, 1996. 161Medical Research Council Lung Cancer Working Party, Lancet 348:563566.1996. L71 Murray N, Grafton C, Shah et al., J Clin Oncol 16:3323-3328.1998. 181 Pignon J-P, Aniagada R, Ihde DC et al., N Engl J med 327:1618-1624. [91 Sagman U, Maki E, Evans WK et al., J Clin Oncol9:1639-1649.1991. 1101 Souhami RL, Spiro SG, Rudd RM et al., J Nat1 Cancer Inst 89:No8 1997. 1111 Steele JPC., Semin Oncol28:15-l&2001. 1121 Thatcher N, Anderson H, Burt P et al., Semin Radiat Oncol5:19-26,1995. [I31 White SC, Lorigan P, Middleton M et al., Cancer 92:601-608 2001.
E-8 1. Small Cell Lung Cancer - Treatment Strategies in the Elderly and Poor Performance Status Patients N. Thatcher CRC Department
of Medical
Oncology,
Christie
Hospital
Lung cancer increases in frequency with age, 40% of patients being over 75 years. Furthermore, 90% of older patients have comorbidity [Brown et al., Thorax 1996; Extermann et al., J Clin 0~01 19981. Treatment aims should reflect the difference in patient prognosis so as not to under-treat the better prognosis patients nor over-treat those with poor prognosis. Furthermore the elderly patient is just as likely to accept treatment but tend to be more conservative in trading off toxicity with likely benefit [Yellen et al., JNCI 19941. Patient groups: Several independent factors carry an adverse prognosis in addition to extensive stage (ES) ie. poor performance status, elevated LDH, alkaline phosphatase and low sodium are the most consistent [Sagman et al., J Clin Oncol 1991; Thatcher et al., Semin Radiat Oncol 19951. Age is not an independent poor prognostic factor. Patients at high risk of dying within the first few weeks of starting chemotherapy tend to have a low PS, be more elderly and with abnormal biochemistry eg. high LDH [Lassen et al., Br J Cancer 1999; Radford et al., Eur J Cancer 19921. Chemotherapy: Given promising phase II data, single agent oral etoposide was thought to be an near ideal therapy for the poorer prognostic elderly groups. However, two large randomised trials demonstrated significantly inferior survival compared with combination iv chemotherapy with no detriment in quality of life or symptomatic relief [Thatcher et al., Lancet 1996; Souhami et al., JNCI 19971. Another randomised trial of two drugs versus four drugs in poor performance status patients also reported lower toxicity with similar survival with the etoposide vincristine doublet combination [Bleehen et al., 19961. Phase II studies have suggested that elderly or infirm LS patients can benefit from just two courses of CAV then PE chemotherapy with concurrent thoracic irradiation [Murray et al., J Clin Onco1 19981. A randomised study compared CAV with single agent carboplatin in a poor prognostic group. There was no significant survival or symptom relief difference but with a lower risk of life threatening sepsis with single agent carboplatin [White et al., Cancer 20011. Nevertheless the search for more effective agents
NHS Trust,
Wilmslow
Road,
Manchester
M20 4BX
UK
continue and oral topotecan has been specifically investigated in an elderly group [Eckardt et al., Lung Cancer 20001. Radiotherapy: For LS patients thoracic radiotherapy can be appropriate. The meta analysis revealed no difference between good and poorer PS patients. However, the survival gain was greatest for patients ~55 years of age and there was a small survival detriment in patients older than 70 years [Pignon et al., NEJM 19921. Prophylactic cranial irradiation with survival gain was not age dependent and there appeared to be no increase in neuropsychological changes in two trials [Auperin NEJM 19991. Conclusion: Elderly, impaired PS patients are underrepresented in trials and there is little data to guide clinical decisions. Further work in defining high risk groups with validation is required to help target treatment more appropriately. For the fit elderly patient standard treatment should be considered. However, for the unfit patients or elderly patients with considerable comorbidity single agent chemotherapy may be appropriate or a fewer number of courses of standard chemotherapy. The comorbidity issues and appropriate supportive care perhaps with agents such as erythropoietin should also be considered.
References 111 Auperin A, Arriagada R, Pignon J-P et al., N Engl J Med 341:476-484,1999.
PJ Eckardt
JR, Palmer MC, Fanucchi MP et al., Lung Cancer (abstr 25), ~10, 2000. M, Overcash j, Lyman GH et al., J Clin Oncol 16:1582131 Extermann 1587,1998. [41 Lassen UN, Osterlind K, Hirsch FR et al., Br J Cancer 79:515-519, 1999. [51 Medical Research Council Lung Cancer Working Party, Br J Cancer 73:406413, 1996. 161Medical Research Council Lung Cancer Working Party, Lancet 348:563566.1996. L71 Murray N, Grafton C, Shah et al., J Clin Oncol 16:3323-3328.1998. 181 Pignon J-P, Aniagada R, Ihde DC et al., N Engl J med 327:1618-1624. [91 Sagman U, Maki E, Evans WK et al., J Clin Oncol9:1639-1649.1991. 1101 Souhami RL, Spiro SG, Rudd RM et al., J Nat1 Cancer Inst 89:No8 1997. 1111 Steele JPC., Semin Oncol28:15-l&2001. 1121 Thatcher N, Anderson H, Burt P et al., Semin Radiat Oncol5:19-26,1995. [I31 White SC, Lorigan P, Middleton M et al., Cancer 92:601-608 2001.