TY - JOUR
T1 - Accelerated methotrexate, vinblastine, doxorubicin, and cisplatin is safe, effective, and efficient neoadjuvant treatment for muscle-invasive bladder cancer
T2 - Results of a multicenter phase II study with molecular correlates of response and toxicity
AU - Plimack, Elizabeth R.
AU - Hoffman-Censits, Jean H.
AU - Viterbo, Rosalia
AU - Trabulsi, Edouard J.
AU - Ross, Eric A.
AU - Greenberg, Richard E.
AU - Chen, David Y.T.
AU - Lallas, Costas D.
AU - Wong, Yu Ning
AU - Lin, Jianqing
AU - Kutikov, Alexander
AU - Dotan, Efrat
AU - Brennan, Timothy A.
AU - Palma, Norma
AU - Dulaimi, Essel
AU - Mehrazin, Reza
AU - Boorjian, Stephen A.
AU - Kelly, William Kevin
AU - Uzzo, Robert G.
AU - Hudes, Gary R.
N1 - © 2014 by American Society of Clinical Oncology.
PY - 2014/5/20
Y1 - 2014/5/20
N2 - 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.
AB - 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.
KW - Aged
KW - Aged, 80 and over
KW - Antineoplastic Combined Chemotherapy Protocols/administration & dosage
KW - Biomarkers, Tumor/analysis
KW - Bone Marrow/drug effects
KW - Carcinoma, Transitional Cell/chemistry
KW - Chemotherapy, Adjuvant
KW - Cisplatin/administration & dosage
KW - Disease-Free Survival
KW - Doxorubicin/administration & dosage
KW - Drug Administration Schedule
KW - Fatigue/chemically induced
KW - Female
KW - Filgrastim
KW - Gene Expression Profiling
KW - Granulocyte Colony-Stimulating Factor/therapeutic use
KW - Humans
KW - Kaplan-Meier Estimate
KW - Male
KW - Methotrexate/administration & dosage
KW - Middle Aged
KW - Neoadjuvant Therapy/methods
KW - Neoplasm Invasiveness
KW - Neoplasm Staging
KW - Polyethylene Glycols
KW - Prospective Studies
KW - Protective Agents/therapeutic use
KW - Recombinant Proteins/therapeutic use
KW - Treatment Outcome
KW - Urinary Bladder Neoplasms/chemistry
KW - Vinblastine/administration & dosage
UR - http://www.scopus.com/inward/record.url?scp=84905500842&partnerID=8YFLogxK
UR - https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=purepublist2023&SrcAuth=WosAPI&KeyUT=WOS:000337901200008&DestLinkType=FullRecord&DestApp=WOS
U2 - 10.1200/JCO.2013.53.2465
DO - 10.1200/JCO.2013.53.2465
M3 - Article
C2 - 24821881
SN - 0732-183X
VL - 32
SP - 1895
EP - 1901
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 18
ER -
