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II TRIAL OF INTRAVESICAL NANOPARTICLE ALBUMIN- BOUND PACLITAXEL FOR THE TREATMENT OF BCG REFRACTORY NON-MUSCLE INVASIVE TRANSITIONAL CELL CARCINOMA
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THE JOURNAL OF UROLOGY姞
Vol. 189, No. 4S, Supplement, Tuesday, May 7, 2013
1697 PROGNOSTIC FACTORS AND RISK GROUPS IN T1G3 PATIENTS INITIALLY TREATED WITH BCG: RESULTS OF A MULTICENTER RETROSPECTIVE SERIES IN 2530 PATIENTS
Source of Funding: None
1696 PHASE I/II TRIAL OF INTRAVESICAL NANOPARTICLE ALBUMIN- BOUND PACLITAXEL FOR THE TREATMENT OF BCG REFRACTORY NON-MUSCLE INVASIVE TRANSITIONAL CELL CARCINOMA Dara Holder*, Crystal Castaneda, Jennifer Ahn, Gina Badalato, LaMont Barlow, Mark Mann, Arindam RoyChoudhury, Mitchell Benson, James Mckiernan, New York, NY INTRODUCTION AND OBJECTIVES: Response rates to current second-line intravesical therapies for non-muscle invasive bladder cancer that recurs after BCG average less than 20%. Nanoparticle albumin-bound (nab-) paclitaxel has been shown to have increased solubility and lower toxicity compared to docetaxel in systemic therapy trials. It is therefore an appropriate candidate for further investigation as an intravesical agent. Results of the Phase I trial demonstrated minimal toxicity and systemic absorption during dose escalation. We now report the updated results of the Phase II trial. METHODS: In January 2010, accrual began for the IRB approved phase II trial investigating the use of nab-paclitaxel for BCG refractory NMIBC. Inclusion criteria included patients with recurrent T1, Tis and high grade (HG) Ta urothelial carcinoma who failed at least one prior regimen of BCG. Patients received 500mg of nab-paclitaxel administered in six weekly intravesical instillations. The primary endpoint was response rate. Efficacy was evaluated by cystoscopy, biopsy, cytology, and imaging. If there was no evidence of disease, patients were treated with monthly maintenance for six months. Safety and toxicity profiles were monitored throughout. RESULTS: As of November 12 2012, twenty-six of the targeted 29 patients have been enrolled with completion enrollment expect in January 2013. The median number of prior BCG induction cycles was 2 with a range of 1-4. Seven patients (27%) had no evidence of disease at their post-treatment cystoscopy and became eligible for maintenance therapy. To date, 7/7 of these patients have remained durably free of disease at a median 13 months. Of the 19 patients who did not respond, no patient had progression of their disease at subsequent TURBT or cystectomy. No patient experienced more than grade 2 side effects. CONCLUSIONS: Intravesical nab-paclitaxel has minimal toxicity and a 27% response rate in patients with non-muscle invasive disease and previous BCG failure. All complete responders have remained disease free after 13 months of follow-up. Source of Funding: Crystal Castaneda is supported by a grant from the Doris Duke Charitable Foundation.
Paolo Gontero*, turin, Italy; Richard Sylvester, Bruxelles, Belgium; Francesca Pisano, Turin, Italy; Steven Joniau, kathy Van der Eeckt, leuven, Belgium; vincenzo serretta, palermo, Italy; stephane larre´, oxford, United Kingdom; savino di stasi, rome, Italy; Bas Van Rhjin, amsterdam, Netherlands; alfred witjes, Nijmegen, Netherlands; Anne Grotenhuis, nijmegen, Netherlands; Renzo Colombo, Alberto Briganti, milano, Italy; Marek Babjuk, Viktor Soukup, praha, Poland; Per Uno Malmstrom, uppsala, Sweden; Jaques Irani, Poitiers, France; Nuria Malats, madrid, Spain; Jack Baniel, Roy Mano, Tel Aviv, Israel; Tommaso Cai, trento, Italy; Eugene Cha, New York, NY; Peter Ardelt, Freiburg, Germany; John Varkarakis, Atene, Greece; Riccardo Bartoletti, Firenze, Italy; Martin Spahn, Wurtzburg, Germany; Juan Palou, barcelona, Spain; Guido Dalbagni, New York, NY; Sharok Shariat, New Yok, NY; Jeffrey Karnes, Rochester, MN INTRODUCTION AND OBJECTIVES: The impact of prognostic factors in T1G3 patients (pts) is critical for proper treatment decision making, however most available data are from small series of pts. The aim of the current study is to assess prognostic factors in a large group of pts who received BCG as initial treatment of T1G3 tumours and identify a subgroup of high risk pts who should be considered for early cystectomy. METHODS: Individual pt data were collected for 2530 pts from 23 centers who received induction or maintenance BCG between 1990 and 2008. Using Cox regression analysis, the prognostic importance of the following variables were assessed for time to recurrence, progression to muscle invasive disease and overall survival: age (⬍ 70 vs ⬎ 70 yrs), gender, primary T1G3 vs recurrent T1G3 after previous non T1G3 tumour, tumour size (⬍ 3 vs ⬎ 3 cm), multiplicity (single vs multiple), concomitant CIS (no/yes), and maintenance BCG (no/yes). RESULTS: Median age was 68 yrs, 82% were male, 89% were primary T1G3, 58% had multifocal disease, 67% had tumours less than 3 cm, 25% had concomitant CIS, 42% had a restaging TUR, 37% received some sort of maintenance BCG. With a follow up out to 15 years, 1300 pts (51%) recurred, 480 (19%) progressed, 523 underwent cystectomy (21%) and 623 (25%) died, 230 (9%) due to bladder cancer. In multivariate analyses, the most important prognostic factors (p ⬍ 0.01) for recurrence were: tumour size and multiplicity; for progression: age, size and concomitant CIS; for overall survival: age and size. Maintenance BCG had a positive impact on recurrence (p ⬍ 0.001), progression (p ⫽ 0.007) and survival (p ⫽ .002). Patients were divided into 4 risk groups according to the number of bad factors for progression among age ⬎ 70, size ⬎ 3 cm and presence of CIS. Progression free rates at 10 yrs were 82%, 73%, 67% and 42% for patients with 0, 1, 2 and 3 bad factors while the corresponding overall survival rates were 78%, 53%, 46% and 16%, respectively. CONCLUSIONS: T1G3 patients treated with BCG have a heterogeneous prognosis, with overall survival at 10 yrs ranging from 78% to 16%. Although maintenance BCG improves outcome as compared to induction alone, fit pts over 70 yrs of age with tumours greater than 3 cm and concomitant CIS should be considered for an early cystectomy. Source of Funding: None
1698 THE IDENTIFICATION OF BCG RESPONSIVE BLADDER CANCER PATIENTS PRIOR TO THERAPY USING A DIAGNOSTIC STRATEGY ASSESSING OF THE TUMOR IMMUNE MICROENVIRONMENT Rafael Nunez-Nateras*, Erin Ferrigni, Cheryl Protheroe, Melissa Stanton, James Lee, Erik Castle, Phoenix, AZ INTRODUCTION AND OBJECTIVES: Transitional cell carcinoma is the most common form of bladder cancer (⬃90% of tumors)
THE JOURNAL OF UROLOGY姞
Vol. 189, No. 4S, Supplement, Tuesday, May 7, 2013
1697 PROGNOSTIC FACTORS AND RISK GROUPS IN T1G3 PATIENTS INITIALLY TREATED WITH BCG: RESULTS OF A MULTICENTER RETROSPECTIVE SERIES IN 2530 PATIENTS
Source of Funding: None
1696 PHASE I/II TRIAL OF INTRAVESICAL NANOPARTICLE ALBUMIN- BOUND PACLITAXEL FOR THE TREATMENT OF BCG REFRACTORY NON-MUSCLE INVASIVE TRANSITIONAL CELL CARCINOMA Dara Holder*, Crystal Castaneda, Jennifer Ahn, Gina Badalato, LaMont Barlow, Mark Mann, Arindam RoyChoudhury, Mitchell Benson, James Mckiernan, New York, NY INTRODUCTION AND OBJECTIVES: Response rates to current second-line intravesical therapies for non-muscle invasive bladder cancer that recurs after BCG average less than 20%. Nanoparticle albumin-bound (nab-) paclitaxel has been shown to have increased solubility and lower toxicity compared to docetaxel in systemic therapy trials. It is therefore an appropriate candidate for further investigation as an intravesical agent. Results of the Phase I trial demonstrated minimal toxicity and systemic absorption during dose escalation. We now report the updated results of the Phase II trial. METHODS: In January 2010, accrual began for the IRB approved phase II trial investigating the use of nab-paclitaxel for BCG refractory NMIBC. Inclusion criteria included patients with recurrent T1, Tis and high grade (HG) Ta urothelial carcinoma who failed at least one prior regimen of BCG. Patients received 500mg of nab-paclitaxel administered in six weekly intravesical instillations. The primary endpoint was response rate. Efficacy was evaluated by cystoscopy, biopsy, cytology, and imaging. If there was no evidence of disease, patients were treated with monthly maintenance for six months. Safety and toxicity profiles were monitored throughout. RESULTS: As of November 12 2012, twenty-six of the targeted 29 patients have been enrolled with completion enrollment expect in January 2013. The median number of prior BCG induction cycles was 2 with a range of 1-4. Seven patients (27%) had no evidence of disease at their post-treatment cystoscopy and became eligible for maintenance therapy. To date, 7/7 of these patients have remained durably free of disease at a median 13 months. Of the 19 patients who did not respond, no patient had progression of their disease at subsequent TURBT or cystectomy. No patient experienced more than grade 2 side effects. CONCLUSIONS: Intravesical nab-paclitaxel has minimal toxicity and a 27% response rate in patients with non-muscle invasive disease and previous BCG failure. All complete responders have remained disease free after 13 months of follow-up. Source of Funding: Crystal Castaneda is supported by a grant from the Doris Duke Charitable Foundation.
Paolo Gontero*, turin, Italy; Richard Sylvester, Bruxelles, Belgium; Francesca Pisano, Turin, Italy; Steven Joniau, kathy Van der Eeckt, leuven, Belgium; vincenzo serretta, palermo, Italy; stephane larre´, oxford, United Kingdom; savino di stasi, rome, Italy; Bas Van Rhjin, amsterdam, Netherlands; alfred witjes, Nijmegen, Netherlands; Anne Grotenhuis, nijmegen, Netherlands; Renzo Colombo, Alberto Briganti, milano, Italy; Marek Babjuk, Viktor Soukup, praha, Poland; Per Uno Malmstrom, uppsala, Sweden; Jaques Irani, Poitiers, France; Nuria Malats, madrid, Spain; Jack Baniel, Roy Mano, Tel Aviv, Israel; Tommaso Cai, trento, Italy; Eugene Cha, New York, NY; Peter Ardelt, Freiburg, Germany; John Varkarakis, Atene, Greece; Riccardo Bartoletti, Firenze, Italy; Martin Spahn, Wurtzburg, Germany; Juan Palou, barcelona, Spain; Guido Dalbagni, New York, NY; Sharok Shariat, New Yok, NY; Jeffrey Karnes, Rochester, MN INTRODUCTION AND OBJECTIVES: The impact of prognostic factors in T1G3 patients (pts) is critical for proper treatment decision making, however most available data are from small series of pts. The aim of the current study is to assess prognostic factors in a large group of pts who received BCG as initial treatment of T1G3 tumours and identify a subgroup of high risk pts who should be considered for early cystectomy. METHODS: Individual pt data were collected for 2530 pts from 23 centers who received induction or maintenance BCG between 1990 and 2008. Using Cox regression analysis, the prognostic importance of the following variables were assessed for time to recurrence, progression to muscle invasive disease and overall survival: age (⬍ 70 vs ⬎ 70 yrs), gender, primary T1G3 vs recurrent T1G3 after previous non T1G3 tumour, tumour size (⬍ 3 vs ⬎ 3 cm), multiplicity (single vs multiple), concomitant CIS (no/yes), and maintenance BCG (no/yes). RESULTS: Median age was 68 yrs, 82% were male, 89% were primary T1G3, 58% had multifocal disease, 67% had tumours less than 3 cm, 25% had concomitant CIS, 42% had a restaging TUR, 37% received some sort of maintenance BCG. With a follow up out to 15 years, 1300 pts (51%) recurred, 480 (19%) progressed, 523 underwent cystectomy (21%) and 623 (25%) died, 230 (9%) due to bladder cancer. In multivariate analyses, the most important prognostic factors (p ⬍ 0.01) for recurrence were: tumour size and multiplicity; for progression: age, size and concomitant CIS; for overall survival: age and size. Maintenance BCG had a positive impact on recurrence (p ⬍ 0.001), progression (p ⫽ 0.007) and survival (p ⫽ .002). Patients were divided into 4 risk groups according to the number of bad factors for progression among age ⬎ 70, size ⬎ 3 cm and presence of CIS. Progression free rates at 10 yrs were 82%, 73%, 67% and 42% for patients with 0, 1, 2 and 3 bad factors while the corresponding overall survival rates were 78%, 53%, 46% and 16%, respectively. CONCLUSIONS: T1G3 patients treated with BCG have a heterogeneous prognosis, with overall survival at 10 yrs ranging from 78% to 16%. Although maintenance BCG improves outcome as compared to induction alone, fit pts over 70 yrs of age with tumours greater than 3 cm and concomitant CIS should be considered for an early cystectomy. Source of Funding: None
1698 THE IDENTIFICATION OF BCG RESPONSIVE BLADDER CANCER PATIENTS PRIOR TO THERAPY USING A DIAGNOSTIC STRATEGY ASSESSING OF THE TUMOR IMMUNE MICROENVIRONMENT Rafael Nunez-Nateras*, Erin Ferrigni, Cheryl Protheroe, Melissa Stanton, James Lee, Erik Castle, Phoenix, AZ INTRODUCTION AND OBJECTIVES: Transitional cell carcinoma is the most common form of bladder cancer (⬃90% of tumors)