Single-Agent Gemcitabine in Previously Untreated Elderly Patients with Advanced Bladder Carcinoma: Response to Treatment and Correlation with the Comprehensive Geriatric

Castagneto, B.; Zai, Silvia; Marenco, Daniela; Bertetto, Oscar; Repetto, Lazzaro; Scaltriti, Laura; Ferraris, V.; Botta, Mario

doi:10.1159/000080282

Cited by 52 publications

(27 citation statements)

References 23 publications

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“…As in first-line trials, it was associated with a wide spectrum of response and survival outcomes depending on the various scheduling and dosing regimens used 11,66,67 . In a phase i study of patients previously treated with mvac, an or rate of 27% was achieved when various doses of gemcitabine were used 68 .…”

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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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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“…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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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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“…Besides, gemcitabine monotherapy has also been shown to be safe and active in previously untreated elderly patients with advanced bladder cancer [3]. Although gemcitabine is widely used in the treatment of solid tumors including lung and breast cancers, to the best of our knowledge, no cases of TLS have been reported in the literature either after treatment with gemcitabine or in metastatic TCC.…”

Section: Discussionmentioning

confidence: 99%

Tumor lysis syndrome after treatment with gemcitabine for metastatic transitional cell carcinoma

et al. 2007

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Tumor lysis syndrome is a set of life threatening complication that can arise from treatment of high tumor burden, drug sensitive, and rapidly proliferating neoplasm particularly of hematological origin. It is rarely described in patients with solid tumors. We report the first case of tumor lysis syndrome in a man with metastatic renal pelvic transitional cell carcinoma after gemcitabine treatment. Despite aggressive therapy, he died 2 weeks after TLS was diagnosed. Our experience demonstrates that administration of gemcitabine for metastatic renal pelvic transitional cell carcinoma may induce acute tumor lysis syndrome, which necessitates frequent laboratory monitoring and prompt initiation of appropriate therapeutic measures.

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Single-Agent Gemcitabine in Previously Untreated Elderly Patients with Advanced Bladder Carcinoma: Response to Treatment and Correlation with the Comprehensive Geriatric

Cited by 52 publications

References 23 publications

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

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

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

Tumor lysis syndrome after treatment with gemcitabine for metastatic transitional cell carcinoma

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