M-Vac (Methotrexate, Vinblastine, Doxorubicin and Cisplatin) for Advanced Transitional Cell Carcinoma of the Urothelium

Sternberg, Cora N.; Yagoda, Alan; Scher, Howard I.; Watson, Robin C.; Herr, Harry W.; Morse, Michael J.; Sogani, Pramod C.; Vaughan, E. Darracott; Bander, Neil H.; Weiselberg, Lora; Geller, Nancy L.; Hollander, Phyllis; Lipperman, Roberta; Fair, William R.; Whitmore, Willet F.

doi:10.1016/s0022-5347(17)42494-3

Cited by 512 publications

(207 citation statements)

References 12 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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“…The combination regimen including methotrexate, vinblastine, doxorubicin and cisplatin (M-VAC) was devised at Memorial Sloan-Kettering in the mid 1980s (Sternberg et al, 1988) and improved overall survival to a median slightly in excess of 12 months and became the standard of care worldwide for advanced bladder cancer (Culine, 2002).…”

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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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“…1 Randomized trials subsequently demonstrated that when applied in the perioperative or metastatic settings, such treatment regimens prolonged patient survival. [2][3][4] However, despite this therapeutic advance, the vast majority of patients with metastatic urothelial cancer, and a large proportion of patients with muscle-invasive disease, will still succumb to their disease.…”

Section: Introductionmentioning

confidence: 99%

Critical analysis of contemporary clinical research in muscle‐invasive and metastatic urothelial cancer

Galsky

Hendricks

Svatek

et al. 2013

Cancer

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BACKGROUND: There have been no improvements in the treatment of metastatic urothelial cancer in the past several decades. A census of contemporary clinical research in this disease was performed to identify potential barriers and opportunities. METHODS: These authors performed a search for clinical trials exploring interventions in muscle-invasive and metastatic urothelial cancer, using the ClinicalTrials.gov registry. Data extracted from the registry included title, recruitment status, interventions, sponsor, phase, enrollment, study design, and study sites. RESULTS: Among 120 eligible trials exploring interventions in muscle-invasive and metastatic urothelial cancer, 73% were phase 2 and 73% were nonrandomized. The majority (63%) involved treatment in the metastatic disease state. The median planned enrollment size per trial was 45 patients (interquartile range, 47 patients). The majority of trials (55%) involved 3 study sites. Trials most commonly explored interventions in the first-line metastatic (30%) or second-line metastatic (37%) settings. Targeted therapeutics were studied in 58% of the trials. Among 56 trials that completed enrollment, the median time to complete accrual was 50 months (range, 10-109 months), and these trials enrolled a median of 40 patients per trial (interquartile range, 44 patients). CONCLUSIONS: The majority of contemporary clinical trials in muscle-invasive and metastatic urothelial cancer are small, nonrandomized, phase 2 trials involving 1 to 3 study sites. Enhanced communication and collaboration among the urothelial cancer community, and other stakeholders, is needed to facilitate the design and conduct of trials capable of expediting progress in this disease.

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M-Vac (Methotrexate, Vinblastine, Doxorubicin and Cisplatin) for Advanced Transitional Cell Carcinoma of the Urothelium

Cited by 512 publications

References 12 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

Critical analysis of contemporary clinical research in muscle‐invasive and metastatic urothelial cancer

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