Eastern Cooperative Oncology Group phase II trial of ifosfamide in the treatment of previously treated advanced urothelial carcinoma.

Witte, Robert S.; Elson, Paul; Bono, Bartholomew R.; Knop, Richard H.; Richardson, Ronald R.; Dreicer, Robert; Loehrer, Patrick J.

doi:10.1200/jco.1997.15.2.589

Cited by 179 publications

(82 citation statements)

References 15 publications

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“…Ifosfamide had been studied in the past, and its phase II results in previously treated patients (not all platinum pretreated) have been somewhat inconsistent with response rates of 1 and of 20% in two studies (Pronzato et al, 1997;Witte et al, 1997). Be that as it may, its use has become less frequent, due to the renal toxicity of Vinflunine salvage therapy for bladder cancer S Culine et al the compound, a particular problem with bladder carcinoma patients who have received prior platinum.…”

Section: Discussionmentioning

confidence: 99%

A phase II study of vinflunine in bladder cancer patients progressing after first-line platinum-containing regimen

et al. 2006

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A multicentre phase II trial to determine the efficacy of vinflunine as second-line therapy in patients with advanced transitional cell carcinoma (TCC) of the bladder; secondary objectives were to assess duration of response, progression-free survival (PFS) and overall survival (OS), and to evaluate the toxicity associated with this treatment. Patients had tumours that failed or progressed after first-line platinum-containing regimens for advanced or metastatic disease, or had progressive disease after platinum-containing chemotherapy given with adjuvant or neoadjuvant intent. Response and adverse events were assessed according to WHO criteria and NCI-CTC (version 2), respectively. Out of 51 patients treated with 320 mg m À2 of vinflunine, nine patients responded to the therapy yielding an overall response rate of 18% (95% CI: 8.4 -30.9%), and 67% (95%CI: 52.1 -79.3%) achieved disease control (PR þ SD). Of note, responses were seen in patients with relatively poor prognostic factors such as a short (o12 months) interval from prior platinum therapy (19%, including an 11% response rate in those progressing o3 months after platinum treatment), prior treatment for metastatic disease (24%), prior treatment with vinca alkaloids (14%) and visceral involvement (20%). The median duration of response was 9.1 months (95% CI: 4.2 -15.0) and the median PFS was 3.0 months (95% CI: 2.4 -3.8). The median OS was 6.6 months (95% CI: 4.8 -7.6). The main haematological toxicity was grade 3 -4 neutropenia, observed in 67% of patients (42% of cycles). Febrile neutropenia was observed in five patients (10%) and among them two were fatal. Constipation was frequently observed (but was manageable and noncumulative) and was grade 3 -4 in only 8% of patients. The incidence of grade 3 nausea and vomiting was very low (4 and 6% of patients, respectively). Neither grade 3 -4 sensory neuropathy nor severe venous irritation was observed. Moreover, and of importance in this particular study population, no grade 3 -4 renal function impairment was observed. Vinflunine is an active agent for the treatment of platinum-pretreated bladder cancer, and these results warrant further investigation in phase III trials, either as monotherapy or in combination with other agents as treatment of advanced/metastatic TCC of the bladder.

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Section: Discussionmentioning

confidence: 99%

A phase II study of vinflunine in bladder cancer patients progressing after first-line platinum-containing regimen

et al. 2006

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“…In examining older agents, only ifosfamide seemed to have shown any promise in this subset of patients. In a phase ii trial, 56 cisplatinpretreated patients received ifosfamide and achieved an or of 20%, with a mds of 5.3 months 49 .…”

Section: Single-agent Second-line Therapymentioning

confidence: 99%

First- and Second-Line Therapy for Metastatic Urothelial Carcinoma of the Bladder

2011

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but little improvement has been achieved in the outcomes of patients with advanced or metastatic disease. Almost 90% of those patients eventually succumb to their cancer.For patients who relapse after first-line chemotherapy, the prognosis is generally poor. To date, there is no real consensus on how to best treat these patients, and most of the available evidence stems from small phase ii trials that have mostly failed to show survival benefit over supportive care. The present review provides an update on the management of metastatic bc, with a focus on first-line and secondline therapies. FIRST-LINE THERAPY Single-Agent TherapySingle-agent therapy has generally failed to provide adequate results in patients with advanced bc. In a phase iii trial of patients randomized to receive either cisplatin alone or in combination [methotrexate, vinblastine, doxorubicin, and cisplatin (mvac)], the overall response rate (or) was only 12% in the cisplatin arm, with only 4 of 122 patients (3.3%) remaining alive at 3 years of follow-up 4 . Similar results were observed in phase ii trials with carboplatin [or: 18%; median duration of survival (mds): 16 months] 5 . In a phase iii trial examining the role of lobaplatin, 2 of 17 patients (12%) achieved a partial response (pr), but the study was terminated because of high toxicity rates 6 . Other drugs investigated in phase ii trials have manifested variable activity against advanced urothelial cancer: oral piritrexim (or: 23%; mds: 22 weeks) 7 , trimetrexate (or: 17%; mds not reported) 8 , and docetaxel (or: 13%; mds: 9 months) 9 . However, some improved results were obtained with other single agents such as paclitaxel and gemcitabine 10,11 . In a phase ii trial of 26 patients with advanced bc treated with paclitaxel, the or was 42%, and the mds, 8.4 months 10 . Similarly, in a phase ii trial of gemcitabine in 40 patients, an or of 28% was reported, with a mds of 54 weeks 11 . ABSTRACTUrothelial cancer of the bladder is the 4th most common malignancy in American men and the 9th most common in women. Although it is a chemosensitive disease, advanced bladder cancer seems to have reached a plateau with regard to median survival of patients. Standard first-line therapy remains gemcitabine plus cisplatin (gc) or methotrexate, vinblastine, doxorubicin, and cisplatin (mvac). In patients deemed unfit to receive cisplatin, gemcitabine plus carboplatin or gemcitabine plus paclitaxel can be considered. To date, no standard therapy has been established for patients who recur or are refractory to first-line therapy. Second-line vinflunine, by way of superiority over best supportive care, has shown promise in a phase iii trial. Cisplatin-based therapy (mvac or gc) can also be offered to patients previously treated with cisplatin, especially if they responded previously and are considered platinum-sensitive. Novel targeted therapies are sorely needed to further improve the delivery and efficacy of chemotherapy.

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“…As a result, there is an expanding, albeit still modest, number of patients with advanced urothelial carcinoma who are fit enough to receive second-line chemotherapy. The 4,9,11,15,16 Witte et al performed a large Phase II trial of ifosfamide that demonstrated a response rate of 20%, with 5 patients obtaining a complete response. However, the toxicity associated with this therapy was not insignificant, with myelosuppression being problematic.…”

Section: Discussionmentioning

confidence: 99%

“…However, the toxicity associated with this therapy was not insignificant, with myelosuppression being problematic. 9 More recently, Lorusso et al administered gemcitabine at a dose of 1200 mg/m 2 weekly for 3 of 4 weeks in patients who previously were treated with cisplatin-based therapy and reported an overall response rate of 22.5%, with 4 patients (13%) achieving a complete response. 17 Albers et al treated cisplatin-refractory patients with gemcitabine, 1250 mg/m 2 , on Days 1 and 8 every 21 days and observed an 11% overall response rate with 2 of the responding patients (7%) obtaining a complete response.…”

Section: Discussionmentioning

confidence: 99%

Phase II trial of gemcitabine and docetaxel in patients with advanced carcinoma of the urothelium

Dreicer

Manola

Schneider

et al. 2003

Cancer

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BACKGROUNDGemcitabine and docetaxel are active agents in advanced urothelial carcinoma. A Phase II trial of this combination was performed to determine the activity and toxicity of these agents in a multiinstitutional setting in patients previously treated with one prior chemotherapy regimen.METHODSTwenty‐nine eligible patients with advanced urothelial carcinoma were treated with docetaxel at a dose of 40 mg/m2 over 1 hour followed by gemcitabine, 800 mg/m2, over 30 minutes, both intravenously (i.v.) on Days 1 and 8. Cycles were repeated every 21 days until disease progression or a maximum of 6 cycles.RESULTSFive patients obtained an objective response for an overall response rate of 17% (90% confidence interval, 7–33%). One patient achieved a complete clinical response. The median overall survival of the group was 7.7 months. Toxicity was moderate with granulocytopenia, anorexia, and fatigue being the most commonly noted side effects.CONCLUSIONSGemcitabine and docetaxel is an active second‐line combination in patients with advanced urothelial carcinoma. Responses in visceral, lymph node, and soft tissues sites were observed. Granulocytopenia without fever, fatigue, and anorexia was common. Thromboembolic symptoms were reported and are of concern. The combination of gemcitabine and docetaxel has the potential to palliate a subset of previously treated patients with an adequate performance status. Cancer 2003;97:2743–7. © 2003 American Cancer Society.DOI 10.1002/cncr.11413

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Eastern Cooperative Oncology Group phase II trial of ifosfamide in the treatment of previously treated advanced urothelial carcinoma.

Abstract: IFX has significant activity, but also major toxicity in a heavily cisplatin-pretreated cohort with advanced urothelial carcinoma. A modification of dose and/or schedule from that described should be considered in future trials. Combination regimens using this agent should be explored.

Cited by 179 publications

References 15 publications

A phase II study of vinflunine in bladder cancer patients progressing after first-line platinum-containing regimen

A phase II study of vinflunine in bladder cancer patients progressing after first-line platinum-containing regimen

First- and Second-Line Therapy for Metastatic Urothelial Carcinoma of the Bladder

Phase II trial of gemcitabine and docetaxel in patients with advanced carcinoma of the urothelium

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