Randomized Phase III Trial of High–Dose-Intensity Methotrexate, Vinblastine, Doxorubicin, and Cisplatin (MVAC) Chemotherapy and Recombinant Human Granulocyte Colony-Stimulating Factor Versus Classic MVAC in Advanced Urothelial Tract Tumors: European Organization for Research and Treatment of Cancer Protocol No. 30924

American Society of Clinical Oncology (ASCO) - Tập 19 Số 10 - Trang 2638-2646 - 2001
Cora N. Sternberg1, P.H.M. de Mulder1, J H Schornagel1, Christine Théodore1, Sophie D. Fosså1, A.T. van Oosterom1, Fred Witjes1, Michele Spina1, C.J. van Groeningen1, Denis Lacombe1, Laurence Collette1
1From the Vincenzo Pansadoro Foundation, Rome, Italy.

Tóm tắt

PURPOSE: This randomized trial evaluated antitumor activity of and survival asociated with high–dose-intensity chemotherapy with methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) plus granulocyte colony-stimulating factor (HD-MVAC) versus MVAC in patients with advanced transitional-cell carcinoma (TCC). PATIENTS AND METHODS: A total of 263 patients with metastatic or advanced TCC who had no prior chemotherapy were randomized to HD-MVAC (2-week cycles) or MVAC (4-week cycles). RESULTS: Using an intent-to-treat analysis, at a median follow-up of 38 months, on the HD-MVAC arm there were 28 complete responses (CRs) (21%) and 55 partial responses (PRs) (41%), for an overall response of 62% (95% confidence interval [CI], 54% to 70%). On the MVAC arm, there were 12 CRs (9%) and 53 PRs (41%), for an overall response of 50% (95% CI, 42% to 59%). The P value for the difference in CR rate was .009; and for the overall response, it was .06. There was no statistically significant difference in survival (P = .122) or time to progression (P = .114). Progression-free survival was significantly better with HD-MVAC (P=.037; hazard ratio .75; 95% CI .58 to .98). The median progression-free survival time was 9.1 months on the HD-MVAC arm versus 8.2 months on the MVAC arm. The 2-year progression-free survival rate was 24.7% for HD-MVAC (95% CI, 17.1% to 32.3%) versus 11.6% for MVAC (95% CI, 5.9% to 17.4%). CONCLUSION: With HD-MVAC, it was possible to deliver twice the doses of cisplatin and doxorubicin in half the time, with fewer dose delays and less toxicity. Although a 50% difference in median overall survival was not detected, a benefit was observed in progression-free survival, CR rates, and overall response rates with HD-MVAC.

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Tài liệu tham khảo

La Vecchia C, Lucchini F, Negri E, et al: Urinary bladder cancer death rates in Europe. Ann Oncol 10: 1529,1999-1530,

10.1002/1097-0142(19891215)64:12<2448::AID-CNCR2820641209>3.0.CO;2-7

10.1200/JCO.1985.3.11.1463

Logothetis CJ, Samuels ML, Selig DE, et al: Combined intravenous and intra-arterial cyclophosphamide, doxorubicin, and cisplatin (CISCA) in the management of select patients with invasive urothelial tumors. Cancer Treat Rep 69: 33,1985-38,

10.1016/S0022-5347(17)48996-8

10.1200/JCO.1990.8.6.1050

10.1200/JCO.1992.10.7.1066

10.1002/1097-0142(19910315)67:6<1525::AID-CNCR2820670611>3.0.CO;2-8

10.1200/JCO.1999.17.10.3173

10.1200/JCO.1997.15.7.2564

10.1056/NEJM198806023182202

10.1093/jnci/82.8.667

10.1093/oxfordjournals.annonc.a058520

10.1200/JCO.1994.12.3.483

Seidman AD, Scher HI, Gabrilove JL, et al: Dose-intensification of methotrexate, vinblastine, doxorubicin, and cisplatin with recombinant granulocyte-colony stimulating factor as initial therapy in advanced urothelial cancer. J Clin Oncol 11: 414,1992-420,

Sternberg CN, de Mulder P, Schornagel J, et al: Randomized phase III trial in advanced urothelial tract tumors of high dose intensity M-VAC chemotherapy and G-CSF versus classic M-VAC. Proc Am Soc Clin Oncol 19: 320a,2000 (abstr 1292)

10.1200/JCO.2000.18.13.2537

10.1200/JCO.2000.18.17.3068

10.1200/JCO.1998.16.1.255

10.1200/JCO.1998.16.5.1844

10.1002/(SICI)1097-0142(20000401)88:7<1671::AID-CNCR22>3.0.CO;2-A

10.1200/JCO.2000.18.18.3247

10.1200/JCO.1997.15.6.2449

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American Society of Clinical Oncology (ASCO)

Tập 19 Số 10

2638-2646

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