- Email: [email protected]
Management of decreased bone mineral density (BMD) in men starting androgen deprivation therapy (ADT) for prostate cancer
S46
Critical Reviews in Oncology/Hematology 68 (2008)
Session X A P.52 Use of sorafenib in elderly patients (EP) affected by metastatic renal cell carcinoma (RCC) according to the Comprehensive Geriatric Assessment (CGA) L. Fratino1 *, C. Simonelli1 , A. Giacalone1 , P. Nigri, I. Sartor1 , L. Tartuferi3 , R. Tedeschi4 , A. Steffan5 , R. Talamini2 , S. Spazzapan1 , M. Berretta1 , E. Vaccher1 , U. Tirelli1 . 1 Division of Medical Oncology, N.C.I., Aviano (PN), Italy, 2 Epidemiology Unit, N. C. I., Aviano (PN), Italy, 3 Cardiology Dep., N. C. I., Aviano (PN), Italy, 4 Division of Microbiology, N. C. I., Aviano (PN), Italy, 5 Unit of Oncology Pathology, N. C. I., Aviano (PN), Italy Purpose of the study: EP represent the prevailing portion of cancer patients, but still few have equal access to efficacious cancer treatments. CGA has been demonstrated as an essential tool to program cancer treatment in EP and a milestone in screening process and decision-making. Presently EP affected by advanced or metastatic RCC have rarely been offered a specific, efficacious treatment. The introduction into clinical practice of multi kinase inhibitors (MTKIs) can represent a new therapeutic option for EP. The present study reports on the use of Sorafenib in EP according to CGA. Summarized description of the project: Since January 2007, we routinely evaluated EP affected by metastatic RCC by means of CGA as a screening tool for decision-making. According to CGA, EP were classified in three risk groups: Fit, Unfit, and Frail. Fit EP who do not fall in unfit or frail definitions. Unfit: EP with mild co-morbidity or functionally mild disabled (e.g. ADL 5 and/or IADL 5); Frail: age >80 years (chronologically frail) or age <80 years with severe co-morbidity and/or higly disabled (functionally frail). Fit and unfit and chronologically frail EP underwent therapy with Sorafenib, whereas functionally frail EP underwent best supportive care. Sorafenib was given 400 mg bid; dose interruption was allowed if grade 3 toxicity occurred. Biochemical and immunological, serum VEGF and bFGF assessment were performed at baseline and during therapy. Results and Conclusions: From January 2007 to May 2008, 23 EP were evaluated. Their median age was 74 years (range 68–82); 75% of EP was affected by one or more co-morbidities that required daily treatment. 20% was fit, 67% unfit and 13% frail according to CGA definition. 18/23 started Sorafenib treatment (800 mg/die; median duration 10 weeks), 2 EP were frail and underwent best supportive care, 2 refused therapy. 12 EP needed therapy discontinuation and 10 EP dose reduction; the most common toxicities were: Fatigue (G3), mucosities (G2), hypertension (G1−2). 4 EP showed PR; 5 showed SD, 4 showed PD (1 switched to sunitinib 1 died for PD) and 5 were not evaluable. The biological findings will be discussed in the meeting. Our experience showed that even in “unfit” EP Sorafenib treatment might be consider a safe and efficacious treatment option. This preliminary observation suggest that EP must not be denied biological therapies because of their age. P.53 Analysis of tolerability and efficacy of sunitinib in elderly patients (70 years) wit metastatic renal cell carcinoma (mRCC) U. Basso1 *, A. Brunello1 , C. Sacco2 , C. Barile3 , M. Cozzi2 , A. Camerini4 , R. De Vivo5 , A. Roma1 , C. Falci1 , A. Jirillo1 , S. Monfardini1 . 1 Istituto Oncologico Veneto-IOV, Padova; 2 University Hospital of Udine, Italy, 3 Medical Oncology, Hospital of Rovigo; 4 Oncology Division, Versilia Hospital, Lucca; 5 San Bortolo Hospital, Vicenza; Italy Background: Sunitinib has shown clinical activity in mRCC. The manageable safety profile and the oral route represent major advantages in treating elderly patients (pts) but actual tolerability is still poorly documented in this age class. Methods: Charts of elderly pts treated with Sunitinib for mRCC were reviewed in five Italian Centers to assess adverse events (primary objective),
Abstracts efficacy and correlation of G3−4 toxicity with multidimensional geriatric assessment (MGA) (secondary objectives). Results: Thirty-six pts were eligible, median age 73.7 years (range 70−82). Associated diseases were present in 32 pts (88.8%), with a mean number of 1.9 comorbidities (range 0−5). Grade 3 or 4 comorbidities according to CIRS-G scale were present in 6 pts. A full MGA was performed in 27 pts, of which 11 (40.7%) were “fit”, 11 pts (40.7%) “vulnerable” and 5 pts (18.6%) “frail”. Median number of cycles was 4.7 (range 1–15), with therapy still ongoing in 22 pts. Dose reduction to 37.5 mg was made upfront because of frailty (11.1%) or after the first cycle for toxicity (41.6%). Toxicities are reported in Table 1. In 9 pts therapy was early interrupted due to rapidly progressive disease (16.6%) or G3−4 toxicity (8.3%: 1 cardiac failure, 1 fatigue, 1 febrile neutropenia). Out of 21 assessable pts, fourteen responses (66.6%) and 5 stabilizations of disease (23.8%) were registered according to treating phyisicians. Progression occurred in 15 patients so far, with a median time to progression of 11.9 months. Correlation was not found between frailty at MGA with G3−4 toxicity nor with response. Conclusions: Our experience shows that treatment with Sunitinib is feasible and effective in elderly pts, even if frail at MGA; yet, adverse events and early interruptions were not uncommon and potential interactions with comorbidities and polypharmacy are still largely unknown, therefore MGA should become routine practice of care in elderly pts receiving targeted therapies. Table 1: Hematological and non-hematological toxicity
Hematological Neutropenia Anemia Thrombocytopenia Non-hematological Nausea/Vomiting Fatigue Hypertension Mucositis Diarrhea Hypothyroidism Hand&foot syndrome Cardiac event
G1−G2 (%)
G3 (%)
G4 (%)
10 (27.7) 14 (38.8) 13 (36.1)
3 (8.3) 2 (5.5) 2(5.5)
1 (2.7) − −
25(69.4) 23(63.8) 19(52.7) 19(52.7) 13(36.1) 12(33.3) 8(22.2) 3(8.3)
− 6(16.7) 1(2.7) − − 2 (5.5) 1 (2.7) 1(2.7)
− − − − − − − −
P.54 Management of decreased bone mineral density (BMD) in men starting androgen deprivation therapy (ADT) for prostate cancer A.H. Panju1,2 *, H. Breunis1 , A. Cheung1,2 , S. Duff-Canning1,2 , N. Fleshner1,2 , M. Krahn1,2 , G. Naglie1,2 , G. Tomlinson1,2 , P. Warde1,2 , S.M.H. Alibhai1,2 . 1 Princess Margaret Hospital, University Health Network, Toronto, Canada, 2 University of Toronto, Toronto, Canada Background: Decreased BMD is a common side effect of androgen deprivation therapy (ADT), leading to increased fracture risk. Little work has been done to determine whether clinicians discuss bone-health side effects with patients on ADT or prescribe lifestyle and pharmacological interventions for low BMD. Methods: Sixty-six men (mean age 70.6 y) with non-metastatic prostate cancer and starting continuous ADT were enrolled in a prospective longitudinal study. BMD was determined by dual x-ray absorptiometry (DXA) at baseline. Patients were interviewed to obtain their medical histories, and clinic notes were reviewed to determine whether clinicians documented potential bone side effects and made lifestyle and/or medication recommendations. Both were done at the start of ADT, three, and six months later. Patients were classified based on DXA T-score as normal BMD, osteopenic, or osteoporotic. Results: At baseline, 53.0% of patients had osteopenia and 4.6% had osteoporosis. Within 6 months of starting ADT, 25.8% of patients were informed of general side effects of ADT, and 15.2% about bone-specific
9th SIOG Meeting, October 16–18, 2008, Montreal, Canada: Posters side effects. BMD test results were noted for 31.8% of patients. Clinicians recommended lifestyle interventions to 10.6% of patients. Pharmacologic interventions (calcium, vitamin D, or bisphosphonates) were recommended to 18.2% of the entire cohort within six months of starting ADT, and to 25.7% and 66.7% of osteopenic and osteoporotic patients, respectively. Conclusion: A minority of patients is being informed of bone-specific side effects of ADT. Lifestyle and drug interventions to prevent BMD declines were uncommonly recommended. Practices around bone health for men starting ADT are suboptimal.
Session X B P.55 Prognostic value of Mini Nutritional Assessment (MNA) score in elderly lung-cancer patients I. Gioulbasanis *, Z. Giannousi, E. Saloustros, L. Vamvakas, A. Karambeazis, N. Androulakis, K. Kalbakis, A. Kotsakis, A. Kalykaki, N. Vardakis. University General Hospital of Heraklion, Department of Medical Oncology, Greece Introduction and Aim: Cachexia has high prevalence in lung cancer patients and influences adversely prognosis, though early symptoms and specific laboratory tests are lacking. MNA score (www.mna-elderly.com) was initially validated for the evaluation of the nutritional status in elderly patients with non-malignant diseases and its value in elderly cancer patients appears interesting. The aim of this study is to evaluate the relation between MNA score with malnutrition and disease’s outcomes, in elderly lung cancer patients. Material and Methods: Elderly patients (>65 years) with lung cancer referred to our clinic within the last 2 years were enrolled. MNA score was applied before the onset of chemotherapy. Patients were divided according to the results into 3 groups: A: MNA score >23.5, adequate nutrition; B: MNA score 17−23.5, risk of malnutrition; C: MNA score <17, malnutrition. Demographic and clinical data, laboratory values indicating cachexia and outcomes were recorded. Results: Totally, 95 patients (89 men) median age (±SD) 72±5.2 years were enrolled. The distribution of patients in the aforementioned groups is illustrated in Table 1. Table 1 Group N (%)
A 24(25.2%)
B 49(47.3%)
C 22(23.1%)
The recorded values per group and correlation between group A versus BC and AB versus C are depicted in Table 2. Table 2 Mean (±SD)
PS Metastatic sites Hb (gr/dl) Albumin (mg/dl) CRP (mg/dl) Transferin (mg/dl) Ferritine (mg/dl) TNF-a (ng/dl) IL-8 (ng/dl) IL-6 (ng/dl)
A
B
C
0.7±0.6 2.3±0.9 13.7±1.8 4.1±0.5 2.7±4.2 248.1±74.8 159.1±127.7 849.6±1529.2 11.3±5.0 6.4±3.9
1.4±0.9 2.7±1.2 12.3±1.8 3.6±0.5 8.0±11.2 195.6±44.0 305.9±319.3 726.7±1850 94.7±190.6 76.6±217.3
2.5±1.2 3.2±1.1 12.4±1.8 3.2±0.4 8.4±6.4 170.4±41.3 317.5±229.6 1022.3±2374.3 389.2±851.9 23.5±18.1
A vs BC
AB vs C
0.001* ns 0.060 <0.001* 0.011* 0.007* 0.096 ns <0.001* 0.027*
<0.001* 0.057 ns <0.001* 0.097 0.022* ns ns 0.093 ns
ns − non significant, *p < 0.05.
Patients with low MNA-score had a higher possibility of receiving monochemotherapy. With a median follow up of 9.5 months (range 0.03– 22.9), There was no relation between MNA score and toxicity (grade 3) on response to treatment [A vs BC (p = 0.51)]; conversely, there was a significant relation with survival [AB vs C (p = 0.026)]. Conclusions: MNA-score is a reliable method for the estimation of the nutritional status in elderly lung cancer patients and is related with prognosis.
S47 P.56 Randomized phase II trial of first-line gefitinib, gemcitabine or docetaxel in performance status (PS) 2 or 3 non-small cell lung cancer (NSCLC) patients (IFCT-0301): elderly patients analysis G. Des Guetz1 *, V. Westeel2 , F. Morin3 , L. Baudrin3 , V. Gounant4 , B. Lebeau5 , F. Vaylet6 , T. Urban7 , F. Barlesi8 , D. Moro-Sibilot9 , P.J. Souquet10 , D. Debieuvre11 , D. Braun12 , G. Fraboulet13 , K. Chouahnia1 , J.F. Morere1 , for the Intergroupe Francophone de Canc´erologie Thoracique (IFCT), Paris, France. 1 Bobigny-Avicenne, 2 Besan¸con-CHU, 3 IFCT, 4 Paris-Tenon, 5 Paris Saint-Antoine, 6 Clamart-Percy, 7 Angers-CHU, 8 Marseille-Hˆ opital Sainte-Marguerite, 9 Grenoble-CHU, 10 Lyon-Sud, 11 Vesoul-CHI, 12 Briey-CHG, 13 Pontoise-CH, France Purpose of the study: PS 2 or 3 patients are usually excluded from clinical trials. Optimal treatment in this setting remains a challenge. The aim of this study was to evaluate 3 monotherapy modalities and better understand causes for compromised PS. Single-agent chemotherapy is considered as a standard for elderly patients (>70). Summarized description of the project: PS 2 or 3 patients with confirmed advanced stage IIIB IV, NSCLC were included into a multicenter randomized phase II trial: arm A, gefitinib (250 mg/day), arm B gemcitabine (1250 mg/m2 , day 1 & 8, every 3 weeks) and arm C docetaxel (75 mg/m2 , day 1, every 3 weeks). Treatments were maintained until progression or unacceptable toxicity. The second-line treatment consisted of: arm A: docetaxel (75 mg/m2 , day 1, every 3 weeks) and arm B/C: gefitinib (250 mg/day). The primary endpoint was Progression Free Survival (PFS). Results: Between December 2004 and June 2007, 128 patients were enrolled. Given the median age in eligible population (n = 127) is 71, an analysis was performed between 2 populations <70 (Y n = 56) and 70 (E n = 71). The characteristics of the 127 eligible patients are the following (Y/E): adenocarcinoma (46%/51 %), PS 2 (62%/75%), PFS (1.4 month, CI95% : [1.1;1.9]/2.3 months, CI95% : [2.1;2.9]), Overall Survival (OS) (2.0 months, CI95% : [1.5;2.4]/ 3.7 months, CI95% : [2.4;4.8]). The results of multivariate analysis are shown in the table.
Arm B C A Histology Squamous Other Adenocarcinoma PS 3 2 Age 70 yrs <70 yrs
Multivariate Cox model PFS
Multivariate Cox model OS
Hazard CI95% Ratio
Hazard CI95% Ratio
p
p
0.76 0.72 1
0.49 to 1.17 0.2130 0.69 0.46 to 1.23 0.1525 0.74 − 1
0.43 to 1.10 0.1201 0.47 to 1.17 0.1975 −
0.87 0.89 1
0.57 to 1.33 0.5130 1.23 0.55 to 1.41 0.6123 0.89 − 1
0.79 to 1.91 0.3561 0.54 to 1.47 0.6516 −
1.27 1
0.86 to 1.87 0.2358 2.00 − 1
1.33 to 3.01 0.0009 −
0.57 1
0.39 to 0.85 0.0053 0.64 − 1
0.42 to 0.96 0.0300 −
Tolerance is similar and acceptable considering young and elderly patients with respectively 37 and 31% gr 3/4. Conclusions: In a multivariate analysis PS 3 patients didn’t benefit of this monotherapy, contrary to elderly patients for PFS and OS. For young patients, monotherapy could be a suboptimal treatment (PFS 1.4 months). Monotherapy for the PS 2 and elderly patients remains a standard.
Critical Reviews in Oncology/Hematology 68 (2008)
Session X A P.52 Use of sorafenib in elderly patients (EP) affected by metastatic renal cell carcinoma (RCC) according to the Comprehensive Geriatric Assessment (CGA) L. Fratino1 *, C. Simonelli1 , A. Giacalone1 , P. Nigri, I. Sartor1 , L. Tartuferi3 , R. Tedeschi4 , A. Steffan5 , R. Talamini2 , S. Spazzapan1 , M. Berretta1 , E. Vaccher1 , U. Tirelli1 . 1 Division of Medical Oncology, N.C.I., Aviano (PN), Italy, 2 Epidemiology Unit, N. C. I., Aviano (PN), Italy, 3 Cardiology Dep., N. C. I., Aviano (PN), Italy, 4 Division of Microbiology, N. C. I., Aviano (PN), Italy, 5 Unit of Oncology Pathology, N. C. I., Aviano (PN), Italy Purpose of the study: EP represent the prevailing portion of cancer patients, but still few have equal access to efficacious cancer treatments. CGA has been demonstrated as an essential tool to program cancer treatment in EP and a milestone in screening process and decision-making. Presently EP affected by advanced or metastatic RCC have rarely been offered a specific, efficacious treatment. The introduction into clinical practice of multi kinase inhibitors (MTKIs) can represent a new therapeutic option for EP. The present study reports on the use of Sorafenib in EP according to CGA. Summarized description of the project: Since January 2007, we routinely evaluated EP affected by metastatic RCC by means of CGA as a screening tool for decision-making. According to CGA, EP were classified in three risk groups: Fit, Unfit, and Frail. Fit EP who do not fall in unfit or frail definitions. Unfit: EP with mild co-morbidity or functionally mild disabled (e.g. ADL 5 and/or IADL 5); Frail: age >80 years (chronologically frail) or age <80 years with severe co-morbidity and/or higly disabled (functionally frail). Fit and unfit and chronologically frail EP underwent therapy with Sorafenib, whereas functionally frail EP underwent best supportive care. Sorafenib was given 400 mg bid; dose interruption was allowed if grade 3 toxicity occurred. Biochemical and immunological, serum VEGF and bFGF assessment were performed at baseline and during therapy. Results and Conclusions: From January 2007 to May 2008, 23 EP were evaluated. Their median age was 74 years (range 68–82); 75% of EP was affected by one or more co-morbidities that required daily treatment. 20% was fit, 67% unfit and 13% frail according to CGA definition. 18/23 started Sorafenib treatment (800 mg/die; median duration 10 weeks), 2 EP were frail and underwent best supportive care, 2 refused therapy. 12 EP needed therapy discontinuation and 10 EP dose reduction; the most common toxicities were: Fatigue (G3), mucosities (G2), hypertension (G1−2). 4 EP showed PR; 5 showed SD, 4 showed PD (1 switched to sunitinib 1 died for PD) and 5 were not evaluable. The biological findings will be discussed in the meeting. Our experience showed that even in “unfit” EP Sorafenib treatment might be consider a safe and efficacious treatment option. This preliminary observation suggest that EP must not be denied biological therapies because of their age. P.53 Analysis of tolerability and efficacy of sunitinib in elderly patients (70 years) wit metastatic renal cell carcinoma (mRCC) U. Basso1 *, A. Brunello1 , C. Sacco2 , C. Barile3 , M. Cozzi2 , A. Camerini4 , R. De Vivo5 , A. Roma1 , C. Falci1 , A. Jirillo1 , S. Monfardini1 . 1 Istituto Oncologico Veneto-IOV, Padova; 2 University Hospital of Udine, Italy, 3 Medical Oncology, Hospital of Rovigo; 4 Oncology Division, Versilia Hospital, Lucca; 5 San Bortolo Hospital, Vicenza; Italy Background: Sunitinib has shown clinical activity in mRCC. The manageable safety profile and the oral route represent major advantages in treating elderly patients (pts) but actual tolerability is still poorly documented in this age class. Methods: Charts of elderly pts treated with Sunitinib for mRCC were reviewed in five Italian Centers to assess adverse events (primary objective),
Abstracts efficacy and correlation of G3−4 toxicity with multidimensional geriatric assessment (MGA) (secondary objectives). Results: Thirty-six pts were eligible, median age 73.7 years (range 70−82). Associated diseases were present in 32 pts (88.8%), with a mean number of 1.9 comorbidities (range 0−5). Grade 3 or 4 comorbidities according to CIRS-G scale were present in 6 pts. A full MGA was performed in 27 pts, of which 11 (40.7%) were “fit”, 11 pts (40.7%) “vulnerable” and 5 pts (18.6%) “frail”. Median number of cycles was 4.7 (range 1–15), with therapy still ongoing in 22 pts. Dose reduction to 37.5 mg was made upfront because of frailty (11.1%) or after the first cycle for toxicity (41.6%). Toxicities are reported in Table 1. In 9 pts therapy was early interrupted due to rapidly progressive disease (16.6%) or G3−4 toxicity (8.3%: 1 cardiac failure, 1 fatigue, 1 febrile neutropenia). Out of 21 assessable pts, fourteen responses (66.6%) and 5 stabilizations of disease (23.8%) were registered according to treating phyisicians. Progression occurred in 15 patients so far, with a median time to progression of 11.9 months. Correlation was not found between frailty at MGA with G3−4 toxicity nor with response. Conclusions: Our experience shows that treatment with Sunitinib is feasible and effective in elderly pts, even if frail at MGA; yet, adverse events and early interruptions were not uncommon and potential interactions with comorbidities and polypharmacy are still largely unknown, therefore MGA should become routine practice of care in elderly pts receiving targeted therapies. Table 1: Hematological and non-hematological toxicity
Hematological Neutropenia Anemia Thrombocytopenia Non-hematological Nausea/Vomiting Fatigue Hypertension Mucositis Diarrhea Hypothyroidism Hand&foot syndrome Cardiac event
G1−G2 (%)
G3 (%)
G4 (%)
10 (27.7) 14 (38.8) 13 (36.1)
3 (8.3) 2 (5.5) 2(5.5)
1 (2.7) − −
25(69.4) 23(63.8) 19(52.7) 19(52.7) 13(36.1) 12(33.3) 8(22.2) 3(8.3)
− 6(16.7) 1(2.7) − − 2 (5.5) 1 (2.7) 1(2.7)
− − − − − − − −
P.54 Management of decreased bone mineral density (BMD) in men starting androgen deprivation therapy (ADT) for prostate cancer A.H. Panju1,2 *, H. Breunis1 , A. Cheung1,2 , S. Duff-Canning1,2 , N. Fleshner1,2 , M. Krahn1,2 , G. Naglie1,2 , G. Tomlinson1,2 , P. Warde1,2 , S.M.H. Alibhai1,2 . 1 Princess Margaret Hospital, University Health Network, Toronto, Canada, 2 University of Toronto, Toronto, Canada Background: Decreased BMD is a common side effect of androgen deprivation therapy (ADT), leading to increased fracture risk. Little work has been done to determine whether clinicians discuss bone-health side effects with patients on ADT or prescribe lifestyle and pharmacological interventions for low BMD. Methods: Sixty-six men (mean age 70.6 y) with non-metastatic prostate cancer and starting continuous ADT were enrolled in a prospective longitudinal study. BMD was determined by dual x-ray absorptiometry (DXA) at baseline. Patients were interviewed to obtain their medical histories, and clinic notes were reviewed to determine whether clinicians documented potential bone side effects and made lifestyle and/or medication recommendations. Both were done at the start of ADT, three, and six months later. Patients were classified based on DXA T-score as normal BMD, osteopenic, or osteoporotic. Results: At baseline, 53.0% of patients had osteopenia and 4.6% had osteoporosis. Within 6 months of starting ADT, 25.8% of patients were informed of general side effects of ADT, and 15.2% about bone-specific
9th SIOG Meeting, October 16–18, 2008, Montreal, Canada: Posters side effects. BMD test results were noted for 31.8% of patients. Clinicians recommended lifestyle interventions to 10.6% of patients. Pharmacologic interventions (calcium, vitamin D, or bisphosphonates) were recommended to 18.2% of the entire cohort within six months of starting ADT, and to 25.7% and 66.7% of osteopenic and osteoporotic patients, respectively. Conclusion: A minority of patients is being informed of bone-specific side effects of ADT. Lifestyle and drug interventions to prevent BMD declines were uncommonly recommended. Practices around bone health for men starting ADT are suboptimal.
Session X B P.55 Prognostic value of Mini Nutritional Assessment (MNA) score in elderly lung-cancer patients I. Gioulbasanis *, Z. Giannousi, E. Saloustros, L. Vamvakas, A. Karambeazis, N. Androulakis, K. Kalbakis, A. Kotsakis, A. Kalykaki, N. Vardakis. University General Hospital of Heraklion, Department of Medical Oncology, Greece Introduction and Aim: Cachexia has high prevalence in lung cancer patients and influences adversely prognosis, though early symptoms and specific laboratory tests are lacking. MNA score (www.mna-elderly.com) was initially validated for the evaluation of the nutritional status in elderly patients with non-malignant diseases and its value in elderly cancer patients appears interesting. The aim of this study is to evaluate the relation between MNA score with malnutrition and disease’s outcomes, in elderly lung cancer patients. Material and Methods: Elderly patients (>65 years) with lung cancer referred to our clinic within the last 2 years were enrolled. MNA score was applied before the onset of chemotherapy. Patients were divided according to the results into 3 groups: A: MNA score >23.5, adequate nutrition; B: MNA score 17−23.5, risk of malnutrition; C: MNA score <17, malnutrition. Demographic and clinical data, laboratory values indicating cachexia and outcomes were recorded. Results: Totally, 95 patients (89 men) median age (±SD) 72±5.2 years were enrolled. The distribution of patients in the aforementioned groups is illustrated in Table 1. Table 1 Group N (%)
A 24(25.2%)
B 49(47.3%)
C 22(23.1%)
The recorded values per group and correlation between group A versus BC and AB versus C are depicted in Table 2. Table 2 Mean (±SD)
PS Metastatic sites Hb (gr/dl) Albumin (mg/dl) CRP (mg/dl) Transferin (mg/dl) Ferritine (mg/dl) TNF-a (ng/dl) IL-8 (ng/dl) IL-6 (ng/dl)
A
B
C
0.7±0.6 2.3±0.9 13.7±1.8 4.1±0.5 2.7±4.2 248.1±74.8 159.1±127.7 849.6±1529.2 11.3±5.0 6.4±3.9
1.4±0.9 2.7±1.2 12.3±1.8 3.6±0.5 8.0±11.2 195.6±44.0 305.9±319.3 726.7±1850 94.7±190.6 76.6±217.3
2.5±1.2 3.2±1.1 12.4±1.8 3.2±0.4 8.4±6.4 170.4±41.3 317.5±229.6 1022.3±2374.3 389.2±851.9 23.5±18.1
A vs BC
AB vs C
0.001* ns 0.060 <0.001* 0.011* 0.007* 0.096 ns <0.001* 0.027*
<0.001* 0.057 ns <0.001* 0.097 0.022* ns ns 0.093 ns
ns − non significant, *p < 0.05.
Patients with low MNA-score had a higher possibility of receiving monochemotherapy. With a median follow up of 9.5 months (range 0.03– 22.9), There was no relation between MNA score and toxicity (grade 3) on response to treatment [A vs BC (p = 0.51)]; conversely, there was a significant relation with survival [AB vs C (p = 0.026)]. Conclusions: MNA-score is a reliable method for the estimation of the nutritional status in elderly lung cancer patients and is related with prognosis.
S47 P.56 Randomized phase II trial of first-line gefitinib, gemcitabine or docetaxel in performance status (PS) 2 or 3 non-small cell lung cancer (NSCLC) patients (IFCT-0301): elderly patients analysis G. Des Guetz1 *, V. Westeel2 , F. Morin3 , L. Baudrin3 , V. Gounant4 , B. Lebeau5 , F. Vaylet6 , T. Urban7 , F. Barlesi8 , D. Moro-Sibilot9 , P.J. Souquet10 , D. Debieuvre11 , D. Braun12 , G. Fraboulet13 , K. Chouahnia1 , J.F. Morere1 , for the Intergroupe Francophone de Canc´erologie Thoracique (IFCT), Paris, France. 1 Bobigny-Avicenne, 2 Besan¸con-CHU, 3 IFCT, 4 Paris-Tenon, 5 Paris Saint-Antoine, 6 Clamart-Percy, 7 Angers-CHU, 8 Marseille-Hˆ opital Sainte-Marguerite, 9 Grenoble-CHU, 10 Lyon-Sud, 11 Vesoul-CHI, 12 Briey-CHG, 13 Pontoise-CH, France Purpose of the study: PS 2 or 3 patients are usually excluded from clinical trials. Optimal treatment in this setting remains a challenge. The aim of this study was to evaluate 3 monotherapy modalities and better understand causes for compromised PS. Single-agent chemotherapy is considered as a standard for elderly patients (>70). Summarized description of the project: PS 2 or 3 patients with confirmed advanced stage IIIB IV, NSCLC were included into a multicenter randomized phase II trial: arm A, gefitinib (250 mg/day), arm B gemcitabine (1250 mg/m2 , day 1 & 8, every 3 weeks) and arm C docetaxel (75 mg/m2 , day 1, every 3 weeks). Treatments were maintained until progression or unacceptable toxicity. The second-line treatment consisted of: arm A: docetaxel (75 mg/m2 , day 1, every 3 weeks) and arm B/C: gefitinib (250 mg/day). The primary endpoint was Progression Free Survival (PFS). Results: Between December 2004 and June 2007, 128 patients were enrolled. Given the median age in eligible population (n = 127) is 71, an analysis was performed between 2 populations <70 (Y n = 56) and 70 (E n = 71). The characteristics of the 127 eligible patients are the following (Y/E): adenocarcinoma (46%/51 %), PS 2 (62%/75%), PFS (1.4 month, CI95% : [1.1;1.9]/2.3 months, CI95% : [2.1;2.9]), Overall Survival (OS) (2.0 months, CI95% : [1.5;2.4]/ 3.7 months, CI95% : [2.4;4.8]). The results of multivariate analysis are shown in the table.
Arm B C A Histology Squamous Other Adenocarcinoma PS 3 2 Age 70 yrs <70 yrs
Multivariate Cox model PFS
Multivariate Cox model OS
Hazard CI95% Ratio
Hazard CI95% Ratio
p
p
0.76 0.72 1
0.49 to 1.17 0.2130 0.69 0.46 to 1.23 0.1525 0.74 − 1
0.43 to 1.10 0.1201 0.47 to 1.17 0.1975 −
0.87 0.89 1
0.57 to 1.33 0.5130 1.23 0.55 to 1.41 0.6123 0.89 − 1
0.79 to 1.91 0.3561 0.54 to 1.47 0.6516 −
1.27 1
0.86 to 1.87 0.2358 2.00 − 1
1.33 to 3.01 0.0009 −
0.57 1
0.39 to 0.85 0.0053 0.64 − 1
0.42 to 0.96 0.0300 −
Tolerance is similar and acceptable considering young and elderly patients with respectively 37 and 31% gr 3/4. Conclusions: In a multivariate analysis PS 3 patients didn’t benefit of this monotherapy, contrary to elderly patients for PFS and OS. For young patients, monotherapy could be a suboptimal treatment (PFS 1.4 months). Monotherapy for the PS 2 and elderly patients remains a standard.