Second Line Chemotherapy with Ifosfamide as Outpatient Treatment for Advanced Bladder Cancer

Pronzato, P.; Vigani, Antonella; Pensa, F.; Vanoli, Maurizio; Tani, Francesco; Vaira, F.

doi:10.1097/00000421-199710000-00018

Cited by 46 publications

(19 citation statements)

References 8 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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“…Metastatic TCC has a poor prognosis, with a median survival that does not exceed 15 months [2]. Therapeutic options are limited and cisplatinbased chemotherapy is the only treatment that improves survival in the first-line setting; however, resistance occurs rapidly and second-line chemotherapy trials have unfortunately yielded discouraging results, with response rates of~10-30%, progression-free survival (PFS) of between 2 and 3 months and a median survival of only 6-9 months [3][4][5][6][7][8][9][10][11][12][13].…”

Section: Introductionmentioning

confidence: 99%

Phase II study of dual phosphoinositol‐3‐kinase (PI3K) and mammalian target of rapamycin (mTOR) inhibitor BEZ235 in patients with locally advanced or metastatic transitional cell carcinoma

et al. 2016

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ObjectiveTo assess, in a multicentre phase II trial, the safety and efficacy of BEZ235, an oral pan-class I phosphoinositol-3-kinase (PI3K) and mammalian target of rapamycin (mTOR) complex1/2 inhibitor, in locally advanced or metastatic transitional cell carcinoma (TCC) after failure of platinumbased therapy. Patients and MethodsPatients with locally advanced or metastatic TCC progressing after platinum therapy were prospectively stratified by PI3K/ Akt/mTOR pathway alterations, defined as PTEN loss and PIK3CA mutation. All patients received BEZ235 until progressive disease or unacceptable toxicity. The primary endpoint was the progression-free survival (PFS) rate at 16 weeks. This study was, however, closed prematurely because BEZ235 was withdrawn from further development. ResultsA total of 20 patients (18 without and two with PI3K/Akt/ mTOR alterations) were enrolled and received BEZ235. One partial response (5%) and two cases of stable disease (10%) were observed, all in patients without PI3K/mTOR pathway alterations. The PFS rate at 8 and 16 weeks was 15 and 10%, respectively; the median (range) PFS was 62 (38-588) days (95% confidence interval [CI] 53-110); and the median (range) overall survival was 127 (41-734) days (95% CI 58-309). Among the 90% of patients who experienced drugrelated adverse events of any grade, 50% experienced grade 3-4 adverse events, including stomatitis (15%), fatigue (5%), nausea (5%), diarrhoea (5%), renal failure (5%), cutaneous rash (5%), hepatotoxicity (5%) and hypertension (5%). ConclusionBEZ235 showed modest clinical activity and an unfavourable toxicity profile in patients with advanced and pretreated TCC; however, a minority of patients experienced a clinical benefit, suggesting that a complete blockade of the PI3K/mTOR axis could improve outcome in some specific patients. Furthermore, this study showed that molecular stratification of patients for personalized medicine before treatment is feasible.

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“…For those patients who are able to receive further treatment, no second-line regimen has been established. Chemotherapeutic agents, including vinflunine (12), pemetrexed (13), paclitaxel (14), docetaxel (15), gemcitabine (16) and ifosfamide (17), are used either as single agent regimens offering a response rate of a maximum of 20% or in combination providing improved response rates without necessarily improved OS, or with substantial cost in terms of toxicity (18)(19)(20)(21)(22)(23).…”

Section: Introductionmentioning

confidence: 99%

Efficacy of weekly paclitaxel treatment as a single agent chemotherapy following first-line cisplatin treatment in urothelial bladder cancer

Sideris

Aoun

Zanaty

et al. 2016

Molecular and Clinical Oncology

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Abstract. The aim of the present study was to investigate the efficacy of paclitaxel following a first-line cisplatin regimen in patients with metastatic bladder cancer. The present study retrospectively evaluated the clinical effects and toxicities of second-line paclitaxel regimens following first-line cisplatin treatment in metastatic bladder cancer. A total of 42 patients with progressing metastatic urothelial bladder cancer following cisplatin-based chemotherapy were enrolled. The patients received weekly treatment with paclitaxel (80 mg/m 2 ) with a median duration of 3 months. The overall response rate, disease control rate and median progression free survival were 9.5, 45.2 and 6.4 months, respectively. Weekly paclitaxel was well-tolerated with rare grade III or IV toxicities. Second-line weekly paclitaxel treatment following first-line cisplatin-based chemotherapy is an effective and well-tolerated regimen in urothelial metastatic bladder cancer.

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Second Line Chemotherapy with Ifosfamide as Outpatient Treatment for Advanced Bladder Cancer

Cited by 46 publications

References 8 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

Phase II study of dual phosphoinositol‐3‐kinase (PI3K) and mammalian target of rapamycin (mTOR) inhibitor BEZ235 in patients with locally advanced or metastatic transitional cell carcinoma

Efficacy of weekly paclitaxel treatment as a single agent chemotherapy following first-line cisplatin treatment in urothelial bladder cancer

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