A randomized comparison of cisplatin alone or in combination with methotrexate, vinblastine, and doxorubicin in patients with metastatic urothelial carcinoma: a cooperative group study.

Loehrer, Patrick J.; Einhorn, Lawrence H.; Elson, Paul; Crawford, E. David; Kuebler, Philip; Tannock, Ian F.; Raghavan, Derek; Stuart-Harris, R.; Sarosdy, Michael F.; Lowe, Bruce A.

doi:10.1200/jco.1992.10.7.1066

Cited by 922 publications

(439 citation statements)

References 21 publications

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“…For this reason, adjuvant systemic chemotherapy should be investigated because good objective responses are observed in a palliative setting [20,21].…”

Section: Discussionmentioning

confidence: 99%

Prognostic factors in urothelial renal pelvis and ureter tumours: a multicentre Rare Cancer Network study

Ozşahin¹,

Zouhair²,

Villà³

et al. 1999

European Journal of Cancer

155

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To assess the prognostic factors in patients with transitional-cell carcinoma of the renal pelvis and/or ureter, a series of 138 patients with transitional-cell carcinoma of the renal pelvis and/or ureter was collected in a retrospective multicentre study. 12 patients with distant metastases were excluded from the statistical evaluation. All but 3 patients underwent radical surgery: nephroureterectomy (n = 71), nephroureterectomy and lymphadenectomy (n = 20), nephroureterectomy and partial bladder resection or transurethral resection (n = 20), nephrectomy (n = 10), and ureterectomy (n = 5). Sixty-one per cent (n = 77) of the tumours were located in the renal pelvis, and 21% (n = 27) in the ureter (both in 22 [17%]). Following surgery, residual tumour was still present in 33 patients (16 microscopic and 17 macroscopic). Postoperative radiotherapy was given to 45 (36%) patients. The median follow-up period was 39 months. In a median period of 9 months, 66% of the patients relapsed (34 local, 7 locoregional, 16 regional, and 24 distant). The 5-and 10-year survival were 29% and 19%, respectively, in all patients. In univariate analyses, statistically signi®cant factors in¯uencing the outcome were Karnofsky index, pT-classi®cation, pN-classi®cation, tumour localisation, grade, and residual tumour after surgery. Multivariate analysis revealed that independent prognostic factors in¯uencing outcome were pTclassi®cation, the existence of residual tumour, and tumour localisation. In patients with urothelial renal pelvis and/or ureter tumours, a radical surgical attitude is mandatory; and the presence of tumour in the ureter is associated with a poorer prognosis. #

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“…For this reason, adjuvant systemic chemotherapy should be investigated because good objective responses are observed in a palliative setting [20,21].…”

Section: Discussionmentioning

confidence: 99%

Prognostic factors in urothelial renal pelvis and ureter tumours: a multicentre Rare Cancer Network study

Ozşahin¹,

Zouhair²,

Villà³

et al. 1999

European Journal of Cancer

155

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“…Treatment with cisplatin, approved for the treatment of advanced disease in the early 1980s, doubled median survival to 8 months (Loehrer et al, 1992).…”

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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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“…4,5 However, this regimen has substantial side effects that can be life threatening: Nausea/emesis, neutropenia, neutropenic fever, mucositis, and renal insufficiency have been reported in a significant proportion of patients, with some toxic deaths reported. 3,4,6 In a recently published trial, a reduced incidence of hematologic and nonhematologic toxicities was reported with the gemcitabine-cisplatin combination compared with M-VAC, although only patients with a good PS and normal renal function were included. 18 New combination regimens have been tested in Phase II studies.…”

Section: Discussionmentioning

confidence: 99%

“…Randomized trials have shown that the M-VAC regimen was superior compared with single-agent cisplatin 4 and compared with the combination of cisplatin, methotrexate, vinblastine, and doxorubicin 5 both in terms of response rates and survival. However, very few patients are long-term survivors, 6 and the toxicities are significant: Grade 3-4 nausea and emesis, 12%; Grade 3-4 neutropenia, 24 -58% (with febrile neutropenia in 10 -25% of patients); severe mucositis, 13-17%; renal failure, 7%; and toxic deaths, 3%.…”

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confidence: 99%

“…However, very few patients are long-term survivors, 6 and the toxicities are significant: Grade 3-4 nausea and emesis, 12%; Grade 3-4 neutropenia, 24 -58% (with febrile neutropenia in 10 -25% of patients); severe mucositis, 13-17%; renal failure, 7%; and toxic deaths, 3%. 3,4 New agents, including gemcitabine, [7][8][9][10] paclitaxel, 11 and docetaxel, 12 have shown activity in patients with bladder and urinary tract transitional cell carcinomas. In Phase II trials, gemcitabine has been combined successfully with cisplatin, [13][14][15] paclitaxel, 16 and paclitaxel plus carboplatin, 17 producing interesting response rates and median survivals.…”

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confidence: 99%

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Gemcitabine plus epirubicin in patients with advanced urothelial carcinoma who are not eligible for platinum‐based regimens

Ricci

Galli²,

Chioni³

et al. 2002

Cancer

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BACKGROUNDThe objective of this study was to evaluate the efficacy and toxicity of gemcitabine plus epirubicin in previously untreated patients with advanced urothelial carcinoma who were not eligible for cisplatin‐based regimens.METHODSPatients with advanced urothelial carcinoma and at least one of the following characteristics were eligible: impaired renal function (creatinine clearance < 60 mL per minute), an Eastern Cooperative Oncology Group performance status (PS) ≥ 2, and age ≥ 75 years. The treatment included epirubicin 70 mg/m2 as an intravenous bolus on Day 1 and gemcitabine 1000 mg/m2 over 30 minutes on Days 1 and 8 of a 21‐day cycle.RESULTSThirty‐eight patients entered the study, and a total of 152 cycles were administered, with a median of 4 cycles per patient (range, 1–6 cycles per patient). The following Grade 3–4 hematologic toxicities were reported (percent of cycles): neutropenia, 22.4%; anemia, 11.2%; and thrombocytopenia, 6.5%. No cardiac, renal, or hepatic toxicities were observed. Dose intensities of epirubicin and gemcitabine were 19.6 mg/m2 per week (84%) and 532.2 mg/m2 per week (80%), respectively. There were 2 complete responses (5.3%), 13 partial responses (34.2%), 11 patients with stable disease (28.9%), and 12 patients with progressive disease (31.6%), for an overall response rate of 39.5% (95% confidence interval, 25.1–55.1). The median progression free survival (PFS) and overall survival (OS) rates were 4.8 months and 8.0 months, respectively. The 1‐year survival rate was 38%, and the median PFS and OS were 6.4 months and 16.4 months, respectively, in patients with PS 0–1. Thirty patients were symptomatic: Seventeen patients (56.7%) achieved a complete response, and 5 patients (16.7%) achieved a partial symptomatic response.CONCLUSIONSAt the doses given in this study, gemcitabine and epirubicin had a good tolerability profile with interesting activity in patients with advanced urothelial carcinoma who were not fit for cisplatin‐based regimens. Cancer 2002;95:1444–50. © 2002 American Cancer Society.DOI 10.1002/cncr.10860

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A randomized comparison of cisplatin alone or in combination with methotrexate, vinblastine, and doxorubicin in patients with metastatic urothelial carcinoma: a cooperative group study.

Abstract: Although a more toxic regimen, we found M-VAC to be superior to single-agent cisplatin with respect to response rate, duration of remission, and overall survival in patients with advanced urothelial carcinoma.

Cited by 922 publications

References 21 publications

Prognostic factors in urothelial renal pelvis and ureter tumours: a multicentre Rare Cancer Network study

Prognostic factors in urothelial renal pelvis and ureter tumours: a multicentre Rare Cancer Network study

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

Gemcitabine plus epirubicin in patients with advanced urothelial carcinoma who are not eligible for platinum‐based regimens

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