Seven year update of an EORTC phase III trial of high dose intensity M-VAC chemotherapy and G-CSF versus classic M-VAC in advanced urothelial tract tumors.

4528 Background: This international randomized trial reports a 7.3 year update of an every 2 week regimen of high-dose-intensity chemotherapy with M-VAC plus G-CSF (HD M-VAC) compared to classic M-VAC (every 4 weeks) in patients (pts) with advanced transitional-cell carcinoma (TCC) (JCO 2001 May 15;19 (10):2638-46).,263 pts with TCC of the urinary tract (bladder, ureter, or renal pelvis), bidimensionally measurable distant metastases, no prior systemic cytotoxic or biologic treatment, and a WHO performance status of 0, or 1 were eligible. Treatment consisted of HD M-VAC: MTX 30mg/m2 d 1,VBL: 3mg/m2 d 2,ADM: 30mg/m2 d 2 and CDDP 70mg/m2 d 2 with G-CSF on d 3-7 in 134 pts vs.,MTX 30mg/m2 d 1,VBL: 3mg/m2 d 2, ADM: 30mg/m2 d 2 and CDDP 70mg/m2 d 2 with MTX and VLB on d 15 and 22. in 129 pts. Using an intent-to-treat analysis, on the HD M-VAC arm there were 28 CRs (21%) and 55 PRs (41%), for an overall RR of 62% (95%CI 54% to 70%). On the M-VAC arm, there were 12 CRs (9%) and 53 PRs (41%), for an overall RR of 50% (95% CI, 42% to 59%). The p value for the difference in CR rate was .009; and for the overall response, was .06.,At a median follow-up of 7.3 years, 213 of 263 (81%) of patients have died. 24.6% are alive on the HD M-VAC arm vs. 13.2% on the M-VAC arm. By intent-to-treat analysis, median progression-free survival was better with HD M-VAC: 9.5 mos (95% CI 7.6-12.2) vs M-VAC 8.1 mos (95% CI 7.0-9.9). (p=.017; HR=0.73; 95% CI 0.56 - 0.95). The median survival was 15 mos and the mortality HR was 0.76 (95% CI: 0.58-0.99). The 2-year survival rate for HD M-VAC was 36.7% (28.3-45.0%) vs 26.2% for M-VAC (95% CI, 18.4%-34.0%). At 5 years, survival was 21.8% in the HD M-VAC arm (95% CI:14.5-29.2%) vs 13.5% (95% CI 7.4-19.6%).There was 1 toxic death in each arm; and more pts died to malignant disease in the M-VAC arm 76% vs 64.9% in the HD M-VAC arm.,With longer follow-up, the initial results have been confirmed. HD M-VAC produces a borderline statistically significant relative reduction in the risk of progression and of the risk of death. No significant financial relationships to disclose.