- Email: [email protected]
Phase II study evaluating safety and efficacy of co-administering propranolol and etodolac for treating cancer cachexia in geriatric patients
S38
2013 SIOG Poster Abstracts
Results: Between 2002 and 2012, 201 prostate cancer patients were treated with Docetaxel of which 182 had mCRPC and 57 (31%) were aged 75 or older with 28% aged ≥ 80 years (our study population). The study population presented with synchronous metastatic disease in 47% of cases, 35% had Gleason score ≥ 8 and a median diagnostic PSA of 43.2 ng/mL. At the start of Docetaxel, most patients presented with isolated bone metastasis (75%) and had an ECOG-PS score ≤ 1 in 78% while 19% had an ECOG-PS score of 2. Treatment was well tolerated (median of 7 cycles) with 11% of patients presenting adverse events grade ≥ 3 and 12% requiring treatment delays. With a median follow up of 26 months, median OS was 19.8 months (95% CI 11.9-27.7). Patients aged 75-79 years had better overall survival when compared to those aged ≥ 80 (median OS 23 months vs 14 months; p = 0.17) with comparable treatment tolerability (Fisher’s exact Chi square p N 0.05). Conclusion: Doc in the context of routine clinical care of elderly patients with mCRPC has manageable toxicity and seems to be as effective as reported in its registration trial, despite a lower median treatment duration. The retrospective design in the setting of a single comprehensive cancer center may overestimate the benefit of this strategy. However no formal geriatric assessment was performed at this time which might underestimate Doc effectiveness as frail patients may have been included under the assumption of fit elders. Disclosure of Interest: None Declared Keywords: Prostate doi:10.1016/j.jgo.2013.09.032
Track 1 - Solid Tumours in the Elderly Lung cancer in eldery patients P031 Phase II study evaluating safety and efficacy of co-administering propranolol and etodolac for treating cancer cachexia in geriatric patients G.S. Bhattacharyya1,*, H. Malhotra2, A. Ranade3, S. Bondarde4, G. Biswas5, T. Shahid6, S. Basu7, N. Bascomb8. 1Medical Oncology, Fortis Hospital, Kolkata; 2Medical Oncology, SMS Medical College, Jaipur; 3 Medical Oncology, Deenanath Mangeshkar Hospital, Pune; 4Medical Oncology, Shatabdi Super Specialty Hospital, Nashik; 5Medical Oncology, Sparsh Hospital, Bhubaneshwar; 6Radiation Oncology, Apollo Hospital; 7 Radiation Oncology, AMRI Hospital, Kolkata, India; 8Drug Development, Vicus Therapeutics, Morris Town, NJ, United States Introduction: Systemic inflammatory response, a characteristic of disease progression in patients with advanced cancer, manifests clinically as cachexia. Many of these patients experience cachexia, pain, and fatigue. This study assessed whether the co-administration of etodolac and propranolol (VT-122) can alleviate cachexia by targeting systemic inflammation in geriatric lung cancer patients. There currently are no approved treatments for cancer cachexia. Beta-adrenergic antagonists and NSAIDs reduce the level of inflammatory cytokines, catecholamines, acute phase proteins, and may attenuate systemic inflammation and the associated clinical manifestations. Objectives: To assess whether the co-administration of etodolac and propranolol (VT-122) can alleviate cachexia by targeting systemic inflammation in geriatric lung cancer patients. Methods: Total of 60 subjects were deemed eligible for this multicenter, randomized, open-label controlled study in weight losing (N5% in prior 2 months) Stage IV NSCLC Geriatric patients not on chemotherapy. 30 subjects subsequently randomized to the control group (Group A) received best supportive care only and the 30 subjects randomized to the treatment arms received best supportive care and VT-122 (coadministration of propranolol and etodolac). Efficacy endpoints included
maintenance of lean body mass (assessed by bioimpedence). Assessments for safety and efficacy were continued for 12 weeks after randomization. Results: SAEs or deaths in the study were attributed not to VT-122 but to underlying disease; AEs attributed to VT-122 were known effects of either propranolol or etodolac. A statistically significant difference was observed in the proportion of subjects (ITT population, LOCF, one patient in Group B did not have a bioimpedance measurement at baseline) who responded with an improvement of ≥5% in LBM at Week 12 (Group A, n = 0/30; Group B, n = 15/30 p = 0.0191). An increasing trend in improvement was seen at Weeks 6 and 9. Conclusion: These (and other supporting) data suggest that the use of VT-122 in patients with advanced cancer who may be receiving concurrent anticancer therapy merits further evaluation. Disclosure of Interest: None Declared Keywords: Drug development doi:10.1016/j.jgo.2013.09.035
Track 1 - Solid Tumours in the Elderly Lung cancer in eldery patients P032 Impact of co-morbidities on gemcitabine as single agent chemotherapy in elderly patients with advanced non-small cell lung cancer (NSCLC) T. Landre1,*, K. Chouahnia2, M.-C. Pailler2, T. Bouillet2, V. Andriambololona2, I. Zelek2, G. Sebbane1, G. Des Guetz1. 1Onco Geriatric Coordination Unit (UCOG), Hôpital René Muret, HUPSSD, APHP, Sevran; 2Oncology, Hôpital Avicenne, HUPSSD, APHP, Bobigny, France Introduction: In the past the unfavourable profile of toxicity of antineoplastic drugs employed as therapy for non small cell lung cancer (NSCLC) (e.g. cisplatinum) limited the role of chemotherapy in the elderly patients with NSCLC. Objectives: To evaluate the impact of co-morbidities on survival in unselected older with NSCLC treated with gemcitabine. Methods: Consecutive elderly patients (aged N 75 years) with NSCLC treated with gemcitabine as single agent therapy were included in this retrospective cohort study. Dose reduction, early discontinuation, toxicities, disease progression, and death were recorded. Impact of age, malnutrition and co-morbidities (classified using the Charlson score) on overall survival was measured. Results: From March 2009 to May 2013, fifty consecutive patients, with a median age of 80 years [range: 75-89], affected by locally advanced (40%), metastatic (34%) or recurrent (26%) NSCLC were enrolled. The study population was mostly made of male patients (88%), smokers or former smokers (80%), with predominantly squamous cell epithelioma (54%) or adenocarcinoma (26%). Gemcitabine (1000 mg/m2 BSA) was administered on days 1-8 every 21 days. Dose reduction and early discontinuation occurred for 8%/14% of patients respectively. None of the patients presented a complete or partial response: 18% showed disease stability and 74% showed disease progression. The main reasons for discontinuing gemcitabine were disease progression (54.5%) and worsening of symptoms (15.9%). Median survival after starting chemotherapy was 7.4 months (ranging from 0.5-30). These last figures were significantly higher in patients with few co-morbidities (Pearson correlation 0.256, P = 0.08). The most common adverse effects were thrombocytopenia and anaemia. Conclusion: In elderly patients with advanced NSCLC, gemcitabine showed good activity with a mild toxicity and could be considered a valid therapeutic option in this setting. Geriatric risk factor as number of co-morbidities seemingly predicted survival. Disclosure of Interest: None Declared
2013 SIOG Poster Abstracts
Results: Between 2002 and 2012, 201 prostate cancer patients were treated with Docetaxel of which 182 had mCRPC and 57 (31%) were aged 75 or older with 28% aged ≥ 80 years (our study population). The study population presented with synchronous metastatic disease in 47% of cases, 35% had Gleason score ≥ 8 and a median diagnostic PSA of 43.2 ng/mL. At the start of Docetaxel, most patients presented with isolated bone metastasis (75%) and had an ECOG-PS score ≤ 1 in 78% while 19% had an ECOG-PS score of 2. Treatment was well tolerated (median of 7 cycles) with 11% of patients presenting adverse events grade ≥ 3 and 12% requiring treatment delays. With a median follow up of 26 months, median OS was 19.8 months (95% CI 11.9-27.7). Patients aged 75-79 years had better overall survival when compared to those aged ≥ 80 (median OS 23 months vs 14 months; p = 0.17) with comparable treatment tolerability (Fisher’s exact Chi square p N 0.05). Conclusion: Doc in the context of routine clinical care of elderly patients with mCRPC has manageable toxicity and seems to be as effective as reported in its registration trial, despite a lower median treatment duration. The retrospective design in the setting of a single comprehensive cancer center may overestimate the benefit of this strategy. However no formal geriatric assessment was performed at this time which might underestimate Doc effectiveness as frail patients may have been included under the assumption of fit elders. Disclosure of Interest: None Declared Keywords: Prostate doi:10.1016/j.jgo.2013.09.032
Track 1 - Solid Tumours in the Elderly Lung cancer in eldery patients P031 Phase II study evaluating safety and efficacy of co-administering propranolol and etodolac for treating cancer cachexia in geriatric patients G.S. Bhattacharyya1,*, H. Malhotra2, A. Ranade3, S. Bondarde4, G. Biswas5, T. Shahid6, S. Basu7, N. Bascomb8. 1Medical Oncology, Fortis Hospital, Kolkata; 2Medical Oncology, SMS Medical College, Jaipur; 3 Medical Oncology, Deenanath Mangeshkar Hospital, Pune; 4Medical Oncology, Shatabdi Super Specialty Hospital, Nashik; 5Medical Oncology, Sparsh Hospital, Bhubaneshwar; 6Radiation Oncology, Apollo Hospital; 7 Radiation Oncology, AMRI Hospital, Kolkata, India; 8Drug Development, Vicus Therapeutics, Morris Town, NJ, United States Introduction: Systemic inflammatory response, a characteristic of disease progression in patients with advanced cancer, manifests clinically as cachexia. Many of these patients experience cachexia, pain, and fatigue. This study assessed whether the co-administration of etodolac and propranolol (VT-122) can alleviate cachexia by targeting systemic inflammation in geriatric lung cancer patients. There currently are no approved treatments for cancer cachexia. Beta-adrenergic antagonists and NSAIDs reduce the level of inflammatory cytokines, catecholamines, acute phase proteins, and may attenuate systemic inflammation and the associated clinical manifestations. Objectives: To assess whether the co-administration of etodolac and propranolol (VT-122) can alleviate cachexia by targeting systemic inflammation in geriatric lung cancer patients. Methods: Total of 60 subjects were deemed eligible for this multicenter, randomized, open-label controlled study in weight losing (N5% in prior 2 months) Stage IV NSCLC Geriatric patients not on chemotherapy. 30 subjects subsequently randomized to the control group (Group A) received best supportive care only and the 30 subjects randomized to the treatment arms received best supportive care and VT-122 (coadministration of propranolol and etodolac). Efficacy endpoints included
maintenance of lean body mass (assessed by bioimpedence). Assessments for safety and efficacy were continued for 12 weeks after randomization. Results: SAEs or deaths in the study were attributed not to VT-122 but to underlying disease; AEs attributed to VT-122 were known effects of either propranolol or etodolac. A statistically significant difference was observed in the proportion of subjects (ITT population, LOCF, one patient in Group B did not have a bioimpedance measurement at baseline) who responded with an improvement of ≥5% in LBM at Week 12 (Group A, n = 0/30; Group B, n = 15/30 p = 0.0191). An increasing trend in improvement was seen at Weeks 6 and 9. Conclusion: These (and other supporting) data suggest that the use of VT-122 in patients with advanced cancer who may be receiving concurrent anticancer therapy merits further evaluation. Disclosure of Interest: None Declared Keywords: Drug development doi:10.1016/j.jgo.2013.09.035
Track 1 - Solid Tumours in the Elderly Lung cancer in eldery patients P032 Impact of co-morbidities on gemcitabine as single agent chemotherapy in elderly patients with advanced non-small cell lung cancer (NSCLC) T. Landre1,*, K. Chouahnia2, M.-C. Pailler2, T. Bouillet2, V. Andriambololona2, I. Zelek2, G. Sebbane1, G. Des Guetz1. 1Onco Geriatric Coordination Unit (UCOG), Hôpital René Muret, HUPSSD, APHP, Sevran; 2Oncology, Hôpital Avicenne, HUPSSD, APHP, Bobigny, France Introduction: In the past the unfavourable profile of toxicity of antineoplastic drugs employed as therapy for non small cell lung cancer (NSCLC) (e.g. cisplatinum) limited the role of chemotherapy in the elderly patients with NSCLC. Objectives: To evaluate the impact of co-morbidities on survival in unselected older with NSCLC treated with gemcitabine. Methods: Consecutive elderly patients (aged N 75 years) with NSCLC treated with gemcitabine as single agent therapy were included in this retrospective cohort study. Dose reduction, early discontinuation, toxicities, disease progression, and death were recorded. Impact of age, malnutrition and co-morbidities (classified using the Charlson score) on overall survival was measured. Results: From March 2009 to May 2013, fifty consecutive patients, with a median age of 80 years [range: 75-89], affected by locally advanced (40%), metastatic (34%) or recurrent (26%) NSCLC were enrolled. The study population was mostly made of male patients (88%), smokers or former smokers (80%), with predominantly squamous cell epithelioma (54%) or adenocarcinoma (26%). Gemcitabine (1000 mg/m2 BSA) was administered on days 1-8 every 21 days. Dose reduction and early discontinuation occurred for 8%/14% of patients respectively. None of the patients presented a complete or partial response: 18% showed disease stability and 74% showed disease progression. The main reasons for discontinuing gemcitabine were disease progression (54.5%) and worsening of symptoms (15.9%). Median survival after starting chemotherapy was 7.4 months (ranging from 0.5-30). These last figures were significantly higher in patients with few co-morbidities (Pearson correlation 0.256, P = 0.08). The most common adverse effects were thrombocytopenia and anaemia. Conclusion: In elderly patients with advanced NSCLC, gemcitabine showed good activity with a mild toxicity and could be considered a valid therapeutic option in this setting. Geriatric risk factor as number of co-morbidities seemingly predicted survival. Disclosure of Interest: None Declared