Elizabeth R Plimack1, Jean H Hoffman-Censits2, Rosalia Viterbo2, Edouard J Trabulsi2, Eric A Ross2, Richard E Greenberg2, David Y T Chen2, Costas D Lallas2, Yu-Ning Wong2, Jianqing Lin2, Alexander Kutikov2, Efrat Dotan2, Timothy A Brennan2, Norma Palma2, Essel Dulaimi2, Reza Mehrazin2, Stephen A Boorjian2, William Kevin Kelly2, Robert G Uzzo2, Gary R Hudes2. 1. Elizabeth R. Plimack, Rosalia Viterbo, Eric A. Ross, Richard E. Greenberg, David Y.T. Chen, Yu-Ning Wong, Alexander Kutikov, Efrat Dotan, Essel Dulaimi, Reza Mehrazin, Robert G. Uzzo, and Gary R. Hudes, Fox Chase Cancer Center, Temple Health; Jean H. Hoffman-Censits, Edouard J. Trabulsi, Costas D. Lallas, Jianqing Lin, and William Kevin Kelly, Thomas Jefferson University Hospital, Philadelphia, PA; Timothy A. Brennan and Norma Palma, Foundation Medicine, Cambridge, MA; and Stephen A. Boorjian, Mayo Clinic, Rochester, MN. elizabeth.plimack@fccc.edu. 2. Elizabeth R. Plimack, Rosalia Viterbo, Eric A. Ross, Richard E. Greenberg, David Y.T. Chen, Yu-Ning Wong, Alexander Kutikov, Efrat Dotan, Essel Dulaimi, Reza Mehrazin, Robert G. Uzzo, and Gary R. Hudes, Fox Chase Cancer Center, Temple Health; Jean H. Hoffman-Censits, Edouard J. Trabulsi, Costas D. Lallas, Jianqing Lin, and William Kevin Kelly, Thomas Jefferson University Hospital, Philadelphia, PA; Timothy A. Brennan and Norma Palma, Foundation Medicine, Cambridge, MA; and Stephen A. Boorjian, Mayo Clinic, Rochester, MN.
Abstract
PURPOSE: Neoadjuvant cisplatin-based chemotherapy is standard of care for muscle-invasive bladder cancer (MIBC); however, it is infrequently adopted in practice because of concerns regarding toxicity and delay to cystectomy. We hypothesized that three cycles of neoadjuvant accelerated methotrexate, vinblastine, doxorubicin, and cisplatin (AMVAC) would be safe, shorten the time to surgery, and yield similar pathologic complete response (pT0) rates compared with historical controls. PATIENTS AND METHODS: Patients with cT2-T4a and N0-N1 MIBC were eligible and received three cycles of AMVAC with pegfilgrastim followed by radical cystectomy with lymph node dissection. The primary end point was pT0 rate. Telomere length (TL) and p53 mutation status were correlated with response and toxicity. RESULTS: Forty-four patients were accrued; 60% had stage III to IV disease; median age was 64 years. Forty patients were evaluable for response, with 15 (38%; 95% CI, 23% to 53%) showing pT0 at cystectomy, meeting the primary end point of the study. Another six patients (14%) were downstaged to non-muscle invasive disease. Most (82%) experienced only grade 1 to 2 treatment-related toxicities. There were no grade 3 or 4 renal toxicities and no treatment-related deaths. One patient developed metastases and thus did not undergo cystectomy; all others (n = 43) proceeded to cystectomy within 8 weeks after last chemotherapy administration. Median time from start of chemotherapy to cystectomy was 9.7 weeks. TL and p53 mutation did not predict response or toxicity. CONCLUSION: AMVAC is well tolerated and results in similar pT0 rates with 6 weeks of treatment compared with standard 12-week regimens. Further analysis is ongoing to ascertain whether molecular alterations in tumor samples can predict response to chemotherapy.
PURPOSE: Neoadjuvant cisplatin-based chemotherapy is standard of care for muscle-invasive bladder cancer (MIBC); however, it is infrequently adopted in practice because of concerns regarding toxicity and delay to cystectomy. We hypothesized that three cycles of neoadjuvant accelerated methotrexate, vinblastine, doxorubicin, and cisplatin (AMVAC) would be safe, shorten the time to surgery, and yield similar pathologic complete response (pT0) rates compared with historical controls. PATIENTS AND METHODS: Patients with cT2-T4a and N0-N1 MIBC were eligible and received three cycles of AMVAC with pegfilgrastim followed by radical cystectomy with lymph node dissection. The primary end point was pT0 rate. Telomere length (TL) and p53 mutation status were correlated with response and toxicity. RESULTS: Forty-four patients were accrued; 60% had stage III to IV disease; median age was 64 years. Forty patients were evaluable for response, with 15 (38%; 95% CI, 23% to 53%) showing pT0 at cystectomy, meeting the primary end point of the study. Another six patients (14%) were downstaged to non-muscle invasive disease. Most (82%) experienced only grade 1 to 2 treatment-related toxicities. There were no grade 3 or 4 renal toxicities and no treatment-related deaths. One patient developed metastases and thus did not undergo cystectomy; all others (n = 43) proceeded to cystectomy within 8 weeks after last chemotherapy administration. Median time from start of chemotherapy to cystectomy was 9.7 weeks. TL and p53 mutation did not predict response or toxicity. CONCLUSION:AMVAC is well tolerated and results in similar pT0 rates with 6 weeks of treatment compared with standard 12-week regimens. Further analysis is ongoing to ascertain whether molecular alterations in tumor samples can predict response to chemotherapy.
Authors: Walter M Stadler; Seth P Lerner; Susan Groshen; John P Stein; Shan-Rong Shi; Derek Raghavan; David Esrig; Gary Steinberg; David Wood; Laurence Klotz; Craig Hall; Donald G Skinner; Richard J Cote Journal: J Clin Oncol Date: 2011-08-01 Impact factor: 44.544
Authors: Pierre A Clavien; Jeffrey Barkun; Michelle L de Oliveira; Jean Nicolas Vauthey; Daniel Dindo; Richard D Schulick; Eduardo de Santibañes; Juan Pekolj; Ksenija Slankamenac; Claudio Bassi; Rolf Graf; René Vonlanthen; Robert Padbury; John L Cameron; Masatoshi Makuuchi Journal: Ann Surg Date: 2009-08 Impact factor: 12.969
Authors: Matthew D Galsky; Noah M Hahn; Jonathan Rosenberg; Guru Sonpavde; Thomas Hutson; William K Oh; Robert Dreicer; Nicholas Vogelzang; Cora Sternberg; Dean F Bajorin; Joaquim Bellmunt Journal: Lancet Oncol Date: 2011-03 Impact factor: 41.316
Authors: Daniel Canter; Christopher Long; Alexander Kutikov; Elizabeth Plimack; Ismail Saad; Megan Oblaczynski; Fang Zhu; Rosalia Viterbo; David Y T Chen; Robert G Uzzo; Richard E Greenberg; Stephen A Boorjian Journal: BJU Int Date: 2011-01 Impact factor: 5.588
Authors: Arnulf Stenzl; Nigel C Cowan; Maria De Santis; Markus A Kuczyk; Axel S Merseburger; Maria José Ribal; Amir Sherif; J Alfred Witjes Journal: Eur Urol Date: 2011-03-23 Impact factor: 20.096
Authors: Uros Milenkovic; Murat Akand; Lisa Moris; Liesbeth Demaegd; Tim Muilwijk; Youri Bekhuis; Annouschka Laenen; Ben Van Cleynenbreugel; Wouter Everaerts; Hein Van Poppel; Herlinde Dumez; Maarten Albersen; Steven Joniau Journal: World J Urol Date: 2018-12-05 Impact factor: 4.226
Authors: Derek E Thomas; Hristos Z Kaimakliotis; Kevin R Rice; Jose A Pereira; Paul Johnston; Marietta L Moore; Angela Reed; Dylan M Cregar; Cindy Franklin; Rhoda L Loman; Michael O Koch; Richard Bihrle; Richard S Foster; Timothy A Masterson; Thomas A Gardner; Chandru P Sundaram; Charles R Powell; Stephen D W Beck; David J Grignon; Liang Cheng; Costantine Albany; Noah M Hahn Journal: Clin Genitourin Cancer Date: 2016-11-30 Impact factor: 2.872
Authors: Benjamin Miron; Jean H Hoffman-Censits; Fern Anari; John O'Neill; Daniel M Geynisman; Matthew R Zibelman; Alexander Kutikov; Rosalia Viterbo; Richard E Greenberg; David Chen; Costas D Lallas; Edouard J Trabulsi; R Katherine Alpaugh; Essel Dulaimi; Erica A Golemis; Robert Uzzo; Eric A Ross; Elizabeth R Plimack Journal: Eur Urol Oncol Date: 2020-03-10
Authors: Ming Yin; Monika Joshi; Richard P Meijer; Michael Glantz; Sheldon Holder; Harold A Harvey; Matthew Kaag; Elisabeth E Fransen van de Putte; Simon Horenblas; Joseph J Drabick Journal: Oncologist Date: 2016-04-06
Authors: Metin Kurtoglu; Nicole N Davarpanah; Rui Qin; Thomas Powles; Jonathan E Rosenberg; Andrea B Apolo Journal: Clin Genitourin Cancer Date: 2015-03-05 Impact factor: 2.872
Authors: Vitaly Margulis; Maneka Puligandla; Edouard J Trabulsi; Elizabeth R Plimack; Elizabeth R Kessler; Surena F Matin; Guilherme Godoy; Ajjai Alva; Noah M Hahn; Michael A Carducci; Jean Hoffman-Censits Journal: J Urol Date: 2019-11-08 Impact factor: 7.450
Authors: Peter E Clark; Philippe E Spiess; Neeraj Agarwal; Rick Bangs; Stephen A Boorjian; Mark K Buyyounouski; Jason A Efstathiou; Thomas W Flaig; Terence Friedlander; Richard E Greenberg; Khurshid A Guru; Noah Hahn; Harry W Herr; Christopher Hoimes; Brant A Inman; A Karim Kader; Adam S Kibel; Timothy M Kuzel; Subodh M Lele; Joshua J Meeks; Jeff Michalski; Jeffrey S Montgomery; Lance C Pagliaro; Sumanta K Pal; Anthony Patterson; Daniel Petrylak; Elizabeth R Plimack; Kamal S Pohar; Michael P Porter; Wade J Sexton; Arlene O Siefker-Radtke; Guru Sonpavde; Jonathan Tward; Geoffrey Wile; Mary A Dwyer; Courtney Smith Journal: J Natl Compr Canc Netw Date: 2016-10 Impact factor: 11.908