Randomized Phase III Study Comparing Paclitaxel/Cisplatin/ Gemcitabine and Gemcitabine/Cisplatin in Patients With Locally Advanced or Metastatic Urothelial Cancer Without Prior Systemic Therapy: EORTC Intergroup Study 30987

Bellmunt, Joaquim; Maase, Hans von der; Mead, G. M.; Skoneczna, Iwona; Santis, Maria De; Daugaard, Gedske; Boehle, Andreas; Chevreau, Christine; Paz‐Ares, Luis; Laufman, Leslie R.; Winquist, Eric; Raghavan, Derek; Marréaud, Sandrine; Collette, Sandra; Sylvester, Richard; Wit, Ronald de

doi:10.1200/jco.2011.38.6979

Cited by 413 publications

(265 citation statements)

References 25 publications

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“…A randomized phase III trial was conducted to compare GC and GC plus paclitaxel in 626 patients with locally advanced or metastatic urothelial cancer. 70 The addition of paclitaxel to GC resulted in higher response rates and a borderline OS advantage, which was not statistically significant in the intent-to-treat analysis. Analysis of eligible patients only (92%) resulted in a small (3.2 months) but statistically significant survival advantage in favor of the 3-drug regimen (P=.03); there was no difference in PFS.…”

Section: Chemotherapy For Metastatic Diseasementioning

confidence: 82%

Bladder Cancer, Version 5.2017, NCCN Clinical Practice Guidelines in Oncology

Spiess¹,

Agarwal²,

Bangs³

et al. 2017

J Natl Compr Canc Netw

220

173

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OverviewAn estimated 79,030 new cases of urinary bladder cancer (60,490 men and 18,540 women) will be diagnosed in the United States in 2017 and approximately 16,870 deaths (12,240 men and 4630 women) will occur. Please NoteThe NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines Disclosures for the NCCN Bladder Cancer PanelAt the beginning of each NCCN Guidelines panel meeting, panel members review all potential conflicts of interest. NCCN, in keeping with its commitment to public transparency, publishes these disclosures for panel members, staff, and NCCN itself.Individual disclosures for the NCCN Bladder Cancer Panel members can be found on page 1267 (The most recent version of these guidelines and accompanying disclosures are available on the NCCN Web site at NCCN.org.)These guidelines are also available on the Internet. For the latest update, visit NCCN.org.

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Section: Chemotherapy For Metastatic Diseasementioning

confidence: 82%

Bladder Cancer, Version 5.2017, NCCN Clinical Practice Guidelines in Oncology

Spiess¹,

Agarwal²,

Bangs³

et al. 2017

J Natl Compr Canc Netw

220

173

View full text Add to dashboard Cite

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“…That result led to the largest-to-date randomized trial in advanced bc, which compared gc with pgc. The pgc combination was found to be associated with a significantly better cr rate (10% vs. 15%, p = 0.02), but no significant improvement in pfs or os was demonstrated 39 . A phase ii trial with a regimen of gemcitabine, paclitaxel, and carboplatin in 49 patients resulted in a cr of 32% and a mds of 14.7 months 40 , but in another phase ii trial using the same regimen, the reported cr was only 12%, and the mds, 11 months 41 .…”

Section: 23mentioning

confidence: 85%

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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“…4,5,7 Patients with metastatic urothelial cancers originating in the upper urinary tract have been previously demonstrated to have inferior outcomes and such tumors may have a different biology than cancers originating in the bladder, despite sharing the same histology. [20][21][22][23] Although the site of the primary tumor did not reach independent prognostic significance on multivariable analysis, this may have been due to an insufficient sample size and the primary tumor site was still included in the final model as per standard nomogram development methodology. We previously identified leukocytosis as a significant predictor of survival in patients with metastatic urothelial cancer in a preliminary analysis.…”

Section: Discussionmentioning

confidence: 99%

Nomogram for predicting survival in patients with unresectable and/or metastatic urothelial cancer who are treated with cisplatin‐based chemotherapy

Galsky

Moshier

Krege³

et al. 2013

Cancer

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BACKGROUND:The current study was conducted to develop a pretreatment prognostic model for patients with unresectable and/or metastatic urothelial cancer who were treated with first-line, cisplatin-based chemotherapy. METHODS: Individual data were pooled from 399 patients who were enrolled on 8 phase 2 and 3 trials evaluating cisplatin-based, first-line chemotherapy in patients with metastatic urothelial carcinoma. Variables selected for inclusion in the model were combined in a Cox proportional hazards model to produce a points-based nomogram with which to predict the median, 1-year, 2-year, and 5-year survival. The nomogram was validated externally using data from a randomized trial of the combination of methotrexate, vinblastine, doxorubicin plus cisplatin versus docetaxel plus cisplatin. RESULTS: The median survival of the development cohort was 13.8 months (95% confidence interval, 12.1 months-16.0 months); 68.2% of the patients had died at the time of last follow-up. On multivariable analysis, the number of visceral metastatic sites, Eastern Cooperative Oncology Group performance status, and leukocyte count were each found to be associated with overall survival (P <.05), whereas the site of the primary tumor and the presence of lymph node metastases were not. All 5 variables were included in the nomogram. When subjected to internal validation, the nomogram achieved a bootstrap-corrected concordance index of 0.626. When applied to the external validation cohort, the nomogram achieved a concordance index of 0.634. Calibration plots suggested that the nomogram was well calibrated for all predictions. CONCLUSIONS: Based on routinely measured pretreatment variables, a nomogram was constructed that predicts survival in patients with unresectable and/or metastatic urothelial cancer who are treated with cisplatin-based chemotherapy. This model may be useful in patient counseling and clinical trial design. Cancer 2013;119:3012-9. V C 2013 American Cancer Society.KEYWORDS: urothelial cancer; bladder cancer; prognosis; metastatic; chemotherapy; cisplatin. INTRODUCTIONContemporary cisplatin-based combination chemotherapy regimens achieve objective responses in approximately 50&percnt to 60% of patients with metastatic urothelial cancer.1,2 Although response durations are generally short, and the median overall survival of patients with unresectable and/or metastatic urothelial cancer is only approximately 14 months, significant heterogeneity exists with regard to patient outcomes.2 Long-term follow-up of clinical trials has demonstrated that approximately 10% to 20% of patients are alive at 5 years.1,3 The ability to predict individual patient outcomes has clear implications with regard to both patient counseling and patient stratification on clinical trials.Prognostic models have previously been developed for chemotherapy-naive patients with unresectable and/or metastatic urothelial cancer. In 1998, Bajorin et al identified Karnofsky performance status and the presence of visceral metastases as independent predictors ...

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Randomized Phase III Study Comparing Paclitaxel/Cisplatin/ Gemcitabine and Gemcitabine/Cisplatin in Patients With Locally Advanced or Metastatic Urothelial Cancer Without Prior Systemic Therapy: EORTC Intergroup Study 30987

Cited by 413 publications

References 25 publications

Bladder Cancer, Version 5.2017, NCCN Clinical Practice Guidelines in Oncology

Bladder Cancer, Version 5.2017, NCCN Clinical Practice Guidelines in Oncology

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

Nomogram for predicting survival in patients with unresectable and/or metastatic urothelial cancer who are treated with cisplatin‐based chemotherapy

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