A phase II study of gemcitabine in patients with transitional cell carcinoma of the urinary tract previously treated with platinum

Lorusso, Vito; Pollera, C. F.; Antimi, Mauro; Luporini, G; Gridelli, Cesare; Frassineti, Giovanni Luca; Oliva, Cristina; Pacini, M.; Lena, M. De

doi:10.1016/s0959-8049(98)00030-6

Cited by 273 publications

(116 citation statements)

References 16 publications

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“…Gemcitabine was developed in the late 1990s and, as a single agent, produced objective response rates ranging from 11 to 29% in second-line (Lorusso et al, 1988;Gebbia et al, 1999;Albers et al, 2002), and of 24 -45% in first-line therapy (Moore et al, 1997;Stadler et al, 1997;Castagneto et al, 2004). A combination regimen of cisplatin and gemcitabine was developed and compared with M-VAC, producing comparable efficacy results, and a reduction of side effects (most notably severe mucositis and infections, as well as alopecia) (Von Der Maase et al, 2000).…”

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

et al. 2006

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“…Similarly, the best treatment for patients who fail to respond to adjuvant intravesical treatment needs further investigation, but cytotoxic drugs could represent an interesting alternative to standard BCG therapy. In this setting, Gemcitabine (Gem), a new generation deoxycytidine analogue, given systemically as a single agent (Lorusso et al, 1998) or in combination with cisplatin, carboplatin or taxanes (Li et al, 2005;Von Der Maase et al, 2005), has proven effective against metastatic bladder lesions, yielding 27 -38% response rates in different studies. Furthermore, pharmacokinetic studies carried out after intravesical instillation have shown a very low systemic absorption of Gem, indicating this drug as an ideal candidate for intravesical therapy (Cozzi et al, 1999;Laufer et al, 2003).…”

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Activity of endovesical gemcitabine in BCG-refractory bladder cancer patients: a translational study

et al. 2007

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Intravesical gemcitabine (Gem) has shown promising activity against transitional cell carcinomas (TCC) of the bladder, with moderate urinary toxicity and low systemic absorption. The present phase II study evaluated the activity of biweekly intravesical treatment with Gem using a scheme directly derived from in vitro preclinical studies. Patients with Bacille Calmette-Guérin (BCG) -refractory Ta G3, T1 G1-3 TCC underwent transurethral bladder resection and then intravesical instillation with 2000 mg Gem diluted in 50 ml saline solution on days 1 and 3 for 6 consecutive weeks. Thirty-eight (95%) of the 40 patients showed persistent negative post-treatment cystoscopy and cytology 6 months after Gem treatment, while the remaining 2 patients relapsed at 5 and 6 months. At a median follow-up of 28 months, recurrences had occurred in 14 patients. Among these, four had downstaged (T) disease, three had a lower grade (G) lesion and three had a reduction in both T and G. Urinary and systemic toxicity was very low, with no alterations in biochemical profiles. In conclusion, biweekly instillation of Gem proved active in BCG-refractory Ta G3, T1 G1-3 TCC. Our results highlight the importance of preclinical studies using in vitro systems that adequately reproduce the conditions of intravesical clinical treatment to define the best therapeutic schedule.

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“…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. 18 McCaffrey et al treated 30 patients with residual or progressive disease after cisplatin-based combination therapy with docetaxel at a dose of 100 mg/m 2 administered on a 3-week schedule.…”

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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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A phase II study of gemcitabine in patients with transitional cell carcinoma of the urinary tract previously treated with platinum

Cited by 273 publications

References 16 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

Activity of endovesical gemcitabine in BCG-refractory bladder cancer patients: a translational study

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

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