Therapy of metastatic bladder carcinoma

Abstract

The methotrexate, vinblastine, doxorubicin, cisplatin (M-VAC) regimen has been considered as standard treatment of metastatic bladder carcinoma till recent years. The superiority of M-VAC both to cisplatin alone and to another cisplatin combination regimen has been demonstrated in randomized studies. During the last years, the use of gemcitabine in metastatic bladder carcinoma has considerably increased, mainly in combination with cisplatin (CG). A phase III trial comparing M-VAC and CG demonstrated similar activity and less toxicity for CG, which has now become the new standard of care for patients with metastatic bladder carcinoma. The substitution of cisplatin with carboplatin, the combination of platinum and taxanes, and the addition of a third drug to basal CG combination represent possible ways to improve outcome. Among the novel cytotoxic compounds, pemetrexed has raised interest, since a phase II second-line study showed a 28% response rate with a manageable toxicity profile. Vinflunine is a novel antitubulin agent with a relevant clinical activity in pretreated metastatic bladder carcinoma (18% response rate, 6.6 months median survival). Novel biologic compounds (in particular drugs targeting epidermal growth factor receptor) are being tested in metastatic bladder carcinoma also and much effort is being pursued in understanding the determinants of tumor response. Crucial mutations to which the tumor becomes addicted have to be discovered so that more effective and specific drugs or combinations can be delivered.

Vinflunine in platinum‐pretreated patients with locally advanced or metastatic urothelial carcinoma

“…[4][5][6] Because patient populations are different between studies, one cannot compare efficacy endpoints among studies.…”

“…Multiple agents against both traditional and novel targets have been studied in small single-arm clinical trials in the second-line setting. [4][5][6] Despite initial enthusiasm for several, none had sufficient robust activity to generate a phase 3 trial.…”

A single‐arm, multicenter, open‐label phase 2 study of lapatinib as the second‐line treatment of patients with locally advanced or metastatic transitional cell carcinoma

“…The relatively high response rate to cisplatin-based chemotherapy and its limited impact on time to disease progression (TTP) and survival leaves a significant patient population in need of salvage therapy, and therefore these patients remain of high unmet medical need. 2,4,17 In several single-and multiple-agent trials in this setting, response rates ranged between 0% and 30%, and survival advantage remains to be elucidated. [18][19][20][21][22][23][24] Tyrosine kinase receptors play a crucial role in the pathobiology of many solid tumors, making them a potential target for novel anticancer agents.…”

Vinflunine in Advanced Transitional Cell Cancer of the Urothelial Tract: A Potential Option for Maintenance Therapy? A Case Series

“…Toxicity remains the major limiting aspect for ifosfamide-containing regimens, while taxanes, alone or in combination, are widely used in cisplatin-refractory TCCU, with ORR ranging from 13% with docetaxel to 40% for paclitaxel-based regimens [7][8][9]. Due to limited therapeutic benefit, none of these treatments have been investigated in phase III trials.…”