| Abstract: |
Purpose: In advanced urothelial cancer, treatment with dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (ddMVAC) results in a high response rate, less toxicity, and few dosing delays. We explored the efficacy and safety of neoadjuvant ddMVAC with pegfilgrastim support in muscleinvasive urothelial cancer (MIUC). Patients and Methods: Patients with cT2-cT4, N0-1, M0 MIUC were enrolled. Four cycles of ddMVAC were administered, followed by radical cystectomy. The primary end point was pathologic response (PaR) defined by pathologic downstaging to ≤ pT1N0M0. The study used Simon's optimal two-stage design to evaluate null and alternative hypotheses of PaR rate of 35% versus 55%. Secondary end points included toxicity, disease-free survival (DFS), radiologic response (RaR), and biomarker correlates, including ERCC1. Results: Between December 2008 and April 2012, 39 patients (cT2N0, 33%; cT3N0, 18%; cT4N0, 3%; cT2-4N1, 43%; unspecified, 3%) were enrolled. Median follow-up was 2 years. Overall, 49% (80% CI, 38 to 61) achieved PaR of ≤ pT1N0M0, and we concluded this regimen was effective. High-grade (grade ≥ 3) toxicities were observed in 10% of patients, with no neutropenic fevers or treatmentrelated death. One-year DFS was 89% versus 67% for patients who achieved PaR compared with those who did not (hazard ratio [HR], 2.6; 95% CI, 0.8 to 8.1; P =.08) and 86% versus 62% for patients who achieved RaR compared with those who did not (HR, 4.1; 95% CI, 1.3 to 12.5; P = .009). We found no association between serum tumor markers or ERCC1 expression with response or survival. Conclusion: In patients with MIUC, neoadjuvant ddMVAC was well tolerated and resulted in significant pathologic and radiologic downstaging. © 2014 by American Society of Clinical Oncology. |
| Keywords: |
immunohistochemistry; adult; clinical article; controlled study; protein expression; treatment outcome; treatment response; aged; aged, 80 and over; disease-free survival; middle aged; cancer surgery; dna binding protein; dna-binding proteins; cisplatin; doxorubicin; cancer combination chemotherapy; drug efficacy; drug safety; drug withdrawal; multimodality cancer therapy; adjuvant therapy; cancer adjuvant therapy; disease free survival; chemotherapy, adjuvant; neoadjuvant therapy; methotrexate; cancer staging; nuclear magnetic resonance imaging; follow up; methodology; follow-up studies; magnetic resonance imaging; antineoplastic agent; neoplasm staging; computer assisted tomography; multiple cycle treatment; phase 2 clinical trial; mucosa inflammation; antineoplastic combined chemotherapy protocols; drug administration schedule; ca 19-9 antigen; tumor markers, biological; creatinine; creatinine blood level; pathology; excision repair cross complementing protein 1; tumor marker; bladder tumor; urinary bladder neoplasms; vinblastine; febrile neutropenia; hypokalemia; chemistry; multicenter study; adjuvant chemotherapy; recombinant proteins; recombinant protein; cystectomy; radiography; open study; neoplasm invasiveness; kaplan meier method; ca 125 antigen; drug administration; endonuclease; recombinant granulocyte colony stimulating factor; carcinoma, transitional cell; transitional cell carcinoma; granulocyte colony stimulating factor; granulocyte colony-stimulating factor; small intestine obstruction; chorionic gonadotropin beta subunit; kaplan-meier estimate; muscle invasive bladder cancer; tumor invasion; endonucleases; protective agents; dose densification; very elderly; humans; human; male; female; priority journal; article; ercc1 protein, human; protective agent
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