Prospective, open-label, randomized, phase III study of two dose-dense regimens MVAC versus gemcitabine/cisplatin in patients with inoperable, metastatic or relapsed urothelial cancer: a Hellenic Cooperative Oncology Group study (HE 16/03)

Ann Oncol. 2013 Apr;24(4):1011-7. doi: 10.1093/annonc/mds583. Epub 2012 Nov 7.

Abstract

Background: The combinations of methotrexate, vinblastine, Adriamycin, cisplatin (Pharmanell, Athens, Greece) (MVAC) or gemcitabine, cisplatin (GC) represent the standard treatment of advanced urothelial cancer (UC). Dose-dense (DD)-MVAC has achieved longer progression-free survival (PFS) than the conventional MVAC. However, the role of GC intensification has not been studied. We conducted a randomized, phase III study comparing a DD-GC regimen with DD-MVAC in advanced UC.

Patients and methods: One hundred and thirty patients were randomly assigned between DD-MVAC: 66 (M 30 mg/m(2), V 3 mg/m(2), A 30 mg/m(2), C 70 mg/m(2) q 2 weeks) and DD-GC 64 (G 2500 mg/m(2), C 70 mg/m(2) q 2 weeks). The median follow-up was 52.1 months (89 events).

Results: The median overall survival (OS) and PFS were 19 and 8.5 months for DD-MVAC and 18 and 7.8 months for DD-GC (P = 0.98 and 0.36, respectively). Neutropenic infections were less frequent for DD-GC than for DD-MVAC (0% versus 8%). More patients on DD-GC received at least six cycles of treatment (85% versus 63%, P = 0.011) and the discontinuation rate was lower for DD-GC (3% versus 13%).

Conclusions: Although DD-GC was not superior to DD-MVAC, it was better tolerated. DD-GC could be considered as a reasonable therapeutic option for further study in this patient population. Clinical Trial Number ACTRN12610000845033, www.anzctr.org.au.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Cisplatin / administration & dosage*
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives*
  • Disease-Free Survival
  • Doxorubicin / administration & dosage
  • Female
  • Humans
  • Male
  • Methotrexate / administration & dosage
  • Middle Aged
  • Neoplasm Staging
  • Prospective Studies
  • Urinary Bladder Neoplasms / drug therapy*
  • Urinary Bladder Neoplasms / pathology*
  • Urinary Bladder Neoplasms / surgery
  • Urothelium / pathology*
  • Urothelium / surgery
  • Vinblastine / administration & dosage

Substances

  • Antineoplastic Agents
  • Deoxycytidine
  • Vinblastine
  • Doxorubicin
  • gemcitabine
  • Cisplatin
  • Methotrexate

Supplementary concepts

  • M-VAC protocol