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P016 Efficacy and safety of intravenous Paclitaxel and metronomic oral Cyclophosphamide for patients with advanced urothelial cancer previously treated with gemcitabine and platinum
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A B S T R A C T S / E U R O P E A N U R O L O G Y S U P P L E M E N T S 12 (2013) 123–180
Material & Methods: Eligible criteria included chemotherapynaïve advanced urothelial carcinoma, ECOG PS 0–2 and measurable disease. Pemetrexed 500 mg/m2 on day 1 with cisplatin 70 mg/m2 on day 1 were administered every 3 weeks till disease progression or a maximal of 8 cycles. Primary endpoint was response rate (RR), and secondary endpoints were progression-free survival (PFS), overall survival (OS) and toxicities. Response was evaluated every 6 weeks according to the RECIST critieria v.1.0 and toxicities were assessed with NCI CTCAE v.3.0 (ClinicalTrials.gov identifier NCT01490437). Results: A total of 42 patients were enrolled and 2 patients were excluded because of different histology and concomitant malignancy. At the time of this analysis, 36 patients (median age 66 years, ECOG 0–1 100%, visceral metastasis 50.0%, recurrent disease 61.1%) were evaluable; 6 patients were too early to assess. Twenty four partial responses for an overall response rate of 66.7% [95% confidence interval (CI) 50.3–79.9%] were documented. Six patients had stable disease. The median PFS was estimated to be 6.9 months [95% CI 6.2–7.7 months]. The median OS was 16.3 months [95% CI 12.9–19.7 months]. The most common grade 3 or 4 toxicities were neutropenia in 33.3% of patients. No one experienced febrile neutropenia. Other grade 3 or 4 hematological and non-hematological toxicities were rarely observed (thrombocytopenia 6%, anemia 6%, LFT elevation 6%, nausea 3%, anorexia 3%, edema 3%, dyspnea 3%). Conclusions: The combination of pemetrexed and cisplatin is clinically very active, with an overall response rate of 66.7% and well tolerated in patients with advanced urothelial cancer who have not been previously treated. P016 Efficacy and safety of intravenous Paclitaxel and metronomic oral Cyclophosphamide for patients with advanced urothelial cancer previously treated with gemcitabine and platinum J.-L. Lee 1 , S. Ahn 2 , I.-G. Jeong 3 , C. Song 3 , B.-S. Hong 3 , J.H. Hong 3 , C.-S. Kim 3 , H. Ahn 3 . 1 Asan Medical Center, University of Ulsan College of Medicine, Dept. of Oncology, Seoul, South Korea; 2 Asan Medical Center, University of Ulsan College of Medicine, Cancer Emergency Room, Asan Cancer Center, Seoul, South Korea; 3 Asan Medical Center, University of Ulsan College of Medicine, Dept. of Urology, Seoul, South Korea Introduction & Objectives: Taxane-based chemotherapy is the most commonly used in patients with advanced uorthelial carcinoma who developed disease progression after gemcitabine and cisplatin combination chemotherapy. However, the response rates have been reported around 10–20%. Recently, promising efficacy results of paclitaxel when combined with oral cyclophosphamide as metronomic therapy was reported. Material & Methods: We retrospectively stuided the patients who were treated with paclitaxel and oral metronomic cyclophosphamide in our institution. Patients received paclitaxel 175 mg/m2 intravenously over 3 hours on day 1 and and cyclophosphamide 50 mg/day orally on days 1–7 every 3 weeks. For patients with ECOG performance status was 2, paclitaxel was given at a dose of 135 mg/m2 for the first cycle and intra-patient dose escalation to 175 mg/m2 was done if clinically significant toxicities were not observed during the first cycle. The primary endpoints were response rate (RECIST v.1.1) and progression-free survival. Results: From March 2012 to May 2013, thirty-three patients with bladder or upper urinary tract cancer were treated with this regimen in our institution after failure to gemcitabine and cisplatin combination chemotherapy. Excluding three patients who had pathology different from urothelial carcinoma (collecting duct carcinoma, small cell carcinoma, and squamous cell carcinoma), 30 patients were included in this study. Platinum-free
interval was less than 6 months in 25 (83%) patients, and 28 (93%) were categorized as having intermediate or poor prognosis according to Bajorin’s criteria. From intentiona-to-treat analysis, there were 8 responses (27%; 95% CI, 11–42%), including one complete response (CR), with a median response duration of 4.3 months. The median time to progression was 2.4 months (95% CI, 2.0–3.0 months) with a median overall survival of 6.3 months (95% CI, 3.0–9.6 months). The most common clinically significant non-hematologic toxicities were peripheral neuropathy (sensory type 48%; motor type 11%), fatigue (39%), and myalgia (37%) but the majorities were grade 1–2 intensities. Grade ≥3 neutropenia occurred in only one patient who developed febrile neutropenia. Conclusions: Paclitaxel and metronomic oral cycleophosphamide was generally well tolerated and demonstrated moderate antitumor activity after gemcitabine-cisplatin failure in patients with urothelial carcinoma but it did not seem to have better activity compared to paclitaxel alone. P017 Vinflunine as second line chemotherapy for patients with metastatic urothelial cancer – A Nordic multi-center retrospective study K. Holmsten 1 , L.H. Dohn 2 , N.V. Jensen 3 , C.-H. Shah 1 , H. Pappot 2 , A. Ullén 1 , NUCOG – Nordic Urothelial Cancer Oncology Group. 1 Karolinska University Hospital, Dept. of Oncology, Stockholm, Sweden; 2 Rigshospitalet, Dept. of Oncology, Copenhagen, Denmark; 3 Odense Universitetshospital, Dept. of Oncology, Odense, Denmark Introduction & Objectives: In 2009 Vinflunine (VFL) was introduced as the first, and so far only approved second line treatment after platinum failure for patients with metastatic transitional cell carcinoma of the urothelium (TCCU). The aim of this study was to analyze treatment patterns, drug-delivery, toxicity and efficacy of VFL-treatment at three Nordic centers. This is, to our knowledge, the largest retrospective study of VFL-treatment in metastatic TCCU. Material & Methods: Medical records based, retrospective analysis of patients with metastatic TCCU treated with VFL following to platinum resistance at cancer centers associated to Nordic Urothelial Cancer Oncology Group (NUCOG). Results: So far, all patients (n=52) treated with VFL at two Nordic centers have been included in the analysis. Patient characteristics concerning sex, age, primary tumor location and previous treatment will be presented in detail at the meeting. Metastatic lesions were distributed as follows: lymph nodes (74%), liver (28%), lung (28%), bone (20%) and other (30%). ECOG PS was 0 in 35%, 1 in 54% and 2 in 11% of the patients. Hemoglobin level was below 10 g/dL in 22%. Furthermore, the median number of VFL cycles were 3 (range 1–21) and treatment initiated most frequently at 280 mg/m2 (49%). 77% of the patients stopped VFL treatment due to disease progression, 14% due to toxicity and 9% due to other reasons. The most frequent grade 3 or 4 toxicities were: anemia (28%), neutropenia (24%), febrile neutropenia (13%), fatigue (20%), abdominal pain (30%) and constipation (22%). Preliminary efficacy data show an ORR of 31% (1 patient with CR) and SD as best response in 23% of the patients. The median PFS and OS were 2.5 months (1.2–14.7) and 4.6 months (0.9–28.5), respectively. For the cohort of patients (67%) that reached the first radiological evaluation (i.e. received >2 cycles), the median OS was 6.2 months (2.4–28.5). Conclusions: Our data confirm that VFL is an active agent for second line treatment in an unselected clinical routine cohort of patients with metastatic TCCU. Interestingly, we observe significant inter-individual differences in treatment efficacy which highlight the importance of proper patient selection and the need for reliable prognostic factors and predictive biomarkers for second line VFL treatment of metastatic TCCU. Final data presented at the
A B S T R A C T S / E U R O P E A N U R O L O G Y S U P P L E M E N T S 12 (2013) 123–180
Material & Methods: Eligible criteria included chemotherapynaïve advanced urothelial carcinoma, ECOG PS 0–2 and measurable disease. Pemetrexed 500 mg/m2 on day 1 with cisplatin 70 mg/m2 on day 1 were administered every 3 weeks till disease progression or a maximal of 8 cycles. Primary endpoint was response rate (RR), and secondary endpoints were progression-free survival (PFS), overall survival (OS) and toxicities. Response was evaluated every 6 weeks according to the RECIST critieria v.1.0 and toxicities were assessed with NCI CTCAE v.3.0 (ClinicalTrials.gov identifier NCT01490437). Results: A total of 42 patients were enrolled and 2 patients were excluded because of different histology and concomitant malignancy. At the time of this analysis, 36 patients (median age 66 years, ECOG 0–1 100%, visceral metastasis 50.0%, recurrent disease 61.1%) were evaluable; 6 patients were too early to assess. Twenty four partial responses for an overall response rate of 66.7% [95% confidence interval (CI) 50.3–79.9%] were documented. Six patients had stable disease. The median PFS was estimated to be 6.9 months [95% CI 6.2–7.7 months]. The median OS was 16.3 months [95% CI 12.9–19.7 months]. The most common grade 3 or 4 toxicities were neutropenia in 33.3% of patients. No one experienced febrile neutropenia. Other grade 3 or 4 hematological and non-hematological toxicities were rarely observed (thrombocytopenia 6%, anemia 6%, LFT elevation 6%, nausea 3%, anorexia 3%, edema 3%, dyspnea 3%). Conclusions: The combination of pemetrexed and cisplatin is clinically very active, with an overall response rate of 66.7% and well tolerated in patients with advanced urothelial cancer who have not been previously treated. P016 Efficacy and safety of intravenous Paclitaxel and metronomic oral Cyclophosphamide for patients with advanced urothelial cancer previously treated with gemcitabine and platinum J.-L. Lee 1 , S. Ahn 2 , I.-G. Jeong 3 , C. Song 3 , B.-S. Hong 3 , J.H. Hong 3 , C.-S. Kim 3 , H. Ahn 3 . 1 Asan Medical Center, University of Ulsan College of Medicine, Dept. of Oncology, Seoul, South Korea; 2 Asan Medical Center, University of Ulsan College of Medicine, Cancer Emergency Room, Asan Cancer Center, Seoul, South Korea; 3 Asan Medical Center, University of Ulsan College of Medicine, Dept. of Urology, Seoul, South Korea Introduction & Objectives: Taxane-based chemotherapy is the most commonly used in patients with advanced uorthelial carcinoma who developed disease progression after gemcitabine and cisplatin combination chemotherapy. However, the response rates have been reported around 10–20%. Recently, promising efficacy results of paclitaxel when combined with oral cyclophosphamide as metronomic therapy was reported. Material & Methods: We retrospectively stuided the patients who were treated with paclitaxel and oral metronomic cyclophosphamide in our institution. Patients received paclitaxel 175 mg/m2 intravenously over 3 hours on day 1 and and cyclophosphamide 50 mg/day orally on days 1–7 every 3 weeks. For patients with ECOG performance status was 2, paclitaxel was given at a dose of 135 mg/m2 for the first cycle and intra-patient dose escalation to 175 mg/m2 was done if clinically significant toxicities were not observed during the first cycle. The primary endpoints were response rate (RECIST v.1.1) and progression-free survival. Results: From March 2012 to May 2013, thirty-three patients with bladder or upper urinary tract cancer were treated with this regimen in our institution after failure to gemcitabine and cisplatin combination chemotherapy. Excluding three patients who had pathology different from urothelial carcinoma (collecting duct carcinoma, small cell carcinoma, and squamous cell carcinoma), 30 patients were included in this study. Platinum-free
interval was less than 6 months in 25 (83%) patients, and 28 (93%) were categorized as having intermediate or poor prognosis according to Bajorin’s criteria. From intentiona-to-treat analysis, there were 8 responses (27%; 95% CI, 11–42%), including one complete response (CR), with a median response duration of 4.3 months. The median time to progression was 2.4 months (95% CI, 2.0–3.0 months) with a median overall survival of 6.3 months (95% CI, 3.0–9.6 months). The most common clinically significant non-hematologic toxicities were peripheral neuropathy (sensory type 48%; motor type 11%), fatigue (39%), and myalgia (37%) but the majorities were grade 1–2 intensities. Grade ≥3 neutropenia occurred in only one patient who developed febrile neutropenia. Conclusions: Paclitaxel and metronomic oral cycleophosphamide was generally well tolerated and demonstrated moderate antitumor activity after gemcitabine-cisplatin failure in patients with urothelial carcinoma but it did not seem to have better activity compared to paclitaxel alone. P017 Vinflunine as second line chemotherapy for patients with metastatic urothelial cancer – A Nordic multi-center retrospective study K. Holmsten 1 , L.H. Dohn 2 , N.V. Jensen 3 , C.-H. Shah 1 , H. Pappot 2 , A. Ullén 1 , NUCOG – Nordic Urothelial Cancer Oncology Group. 1 Karolinska University Hospital, Dept. of Oncology, Stockholm, Sweden; 2 Rigshospitalet, Dept. of Oncology, Copenhagen, Denmark; 3 Odense Universitetshospital, Dept. of Oncology, Odense, Denmark Introduction & Objectives: In 2009 Vinflunine (VFL) was introduced as the first, and so far only approved second line treatment after platinum failure for patients with metastatic transitional cell carcinoma of the urothelium (TCCU). The aim of this study was to analyze treatment patterns, drug-delivery, toxicity and efficacy of VFL-treatment at three Nordic centers. This is, to our knowledge, the largest retrospective study of VFL-treatment in metastatic TCCU. Material & Methods: Medical records based, retrospective analysis of patients with metastatic TCCU treated with VFL following to platinum resistance at cancer centers associated to Nordic Urothelial Cancer Oncology Group (NUCOG). Results: So far, all patients (n=52) treated with VFL at two Nordic centers have been included in the analysis. Patient characteristics concerning sex, age, primary tumor location and previous treatment will be presented in detail at the meeting. Metastatic lesions were distributed as follows: lymph nodes (74%), liver (28%), lung (28%), bone (20%) and other (30%). ECOG PS was 0 in 35%, 1 in 54% and 2 in 11% of the patients. Hemoglobin level was below 10 g/dL in 22%. Furthermore, the median number of VFL cycles were 3 (range 1–21) and treatment initiated most frequently at 280 mg/m2 (49%). 77% of the patients stopped VFL treatment due to disease progression, 14% due to toxicity and 9% due to other reasons. The most frequent grade 3 or 4 toxicities were: anemia (28%), neutropenia (24%), febrile neutropenia (13%), fatigue (20%), abdominal pain (30%) and constipation (22%). Preliminary efficacy data show an ORR of 31% (1 patient with CR) and SD as best response in 23% of the patients. The median PFS and OS were 2.5 months (1.2–14.7) and 4.6 months (0.9–28.5), respectively. For the cohort of patients (67%) that reached the first radiological evaluation (i.e. received >2 cycles), the median OS was 6.2 months (2.4–28.5). Conclusions: Our data confirm that VFL is an active agent for second line treatment in an unselected clinical routine cohort of patients with metastatic TCCU. Interestingly, we observe significant inter-individual differences in treatment efficacy which highlight the importance of proper patient selection and the need for reliable prognostic factors and predictive biomarkers for second line VFL treatment of metastatic TCCU. Final data presented at the