Phase I-II Study of Paclitaxel, Cisplatin, and Gemcitabine in Advanced Transitional-Cell Carcinoma of the Urothelium

Bellmunt, Joaquim; Guillém, Vicente; Paz‐Ares, Luis; Gonzalez-Larriba, J. L.; Carles, Joan; Batiste-Alentorn, E.; Saenz, A.; López‐Brea, Marta; Font, Albert; Nogué, Miquel; Bastús, R.; Climent, Miguel Ángel; Cruz, Juan; Albanell, Joan; Banús, J.M.; Gallardo, Enrique; Díaz-Rubio, Eduardo; Cortés, Javier; Baselga, J.

doi:10.1200/jco.2000.18.18.3247

Cited by 187 publications

(81 citation statements)

References 31 publications

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“…203 In phase 2 studies, paclitaxel has been shown to be effective both as a single agent and in combination with gemcitabine and/or cisplatin. [204][205][206] Poor renal function prohibits the use of cisplatin-based regimens, and thus, carboplatin was used with the intent of providing similar efficacy to cisplatin with less renal toxicity. 207 A study of the paclitaxel, carboplatin, and gemcitabine regimen was shown to have a high response rate and median survival of 14.7 months, making this regimen a potential alternative to cisplatin-based chemotherapy.…”

Section: Urinary Diversionmentioning

confidence: 99%

Bladder Cancer in 2010: How Far have We Come?

Jacobs¹,

Lee

Montie

2010

CA: A Cancer Journal for Clinicians

300

275

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Bladder cancer is the fourth most common cancer and ranks eighth as a cause of death from cancer among men in the United States. Although guidelines assist in treatment, the art of managing bladder cancer, such as the decision to use neoadjuvant chemotherapy and the timing of cystectomy, is still variable. Bladder cancer has a propensity to recur, and with recurrence, a significant number of cases progress, which makes the early detection of high-risk patients imperative. Advances in detection, surveillance, and treatment of bladder cancer are reviewed in this article.

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Section: Urinary Diversionmentioning

confidence: 99%

Bladder Cancer in 2010: How Far have We Come?

Jacobs¹,

Lee

Montie

2010

CA: A Cancer Journal for Clinicians

300

275

View full text Add to dashboard Cite

show abstract

“…The combination of paclitaxel, gemcitabine and cisplatin (Bellmunt et al, 2000); the one with ifosfamide, paclitaxel and cisplatin (Bajorin et al, 1998); and one with paclitaxel, gemcitabine and carboplatin (Hussain et al, 2001) showed promising activity with predominantly haematological toxicity. The last study was comprised of patients with normal and poor renal function (Hussain et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

Phase II multicentre study of docetaxel plus cisplatin in patients with advanced urothelial cancer

Muro

Marcuello

Gumà³

et al. 2002

Br J Cancer

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A multicentre phase II trial was undertaken to evaluate the activity and toxicity of docetaxel plus cisplatin as first-line chemotherapy in patients with urothelial cancer. Thirty-eight patients with locally advanced or metastatic transitional-cell carcinoma of the bladder, renal pelvis or ureter received the combination of docetaxel 75 mg m 72 and cisplatin 75 mg m 72 on day 1 and repeated every 21 days, to a maximum of six cycles. The median delivered dose-intensity was 98% (range 79 -102%) of the planned dose for both drugs. There were seven complete responses and 15 partial responses, for and overall response rate of 58% (95% CI, 41 -74%). Responses were even seen in three patients with hepatic metastases. The median time to progression was 6.9 months, and the median overall survival was 10.4 months. Two patients who achieved CR status remain free of disease at 4 and 3 years respectively. Grade 3 -4 granulocytopenia occurred in 27 patients, resulting in five episodes of febrile neutropenia. There was one toxic death in a patient with grade 4 granulocytopenia who developed acute abdomen. Grade 3 -4 thrombocytopenia was rare (one patient). Other grade 3 -4 toxicities observed were anaemia (three patients), vomiting (five patients), diarrhoea (four patients), peripheral neuropathy (two patients) and non-neutropenic infections (seven patients). Docetaxel plus cisplatin is an effective and well-tolerated regimen for the treatment of advanced urothelial cancer, and warrants further investigation.

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“…In support of DNA methylation in small-cell bladder carcinoma PH Abbosh et al this theory, novel chemotherapy regimens, which include microtubule-targeting agents for TCC, are currently being explored and have shown promising results. 33,34 In addition, one case of a sustained response of SCBC to a paclitaxel-based regimen has been reported. 35 In our study, 86% of patients had methylation in at least one component of their bladder tumors.…”

Section: Discussionmentioning

confidence: 99%

Hypermethylation of tumor-suppressor gene CpG islands in small-cell carcinoma of the urinary bladder

et al. 2008

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Small-cell carcinoma of the urinary bladder (SCBC) is a rare tumor, which shows a common clonal origin with urothelial carcinoma. It bears a high metastatic potential, even when discovered in a localized state. Identifying the molecular underpinnings of this disease may elucidate useful clinical information regarding prevention, diagnosis, prognosis, treatment, and surveillance. As DNA methylation is widely recognized as having a pivotal role in the process of carcinogenesis, we analyzed the DNA methylation status of four frequently hypermethylated tumor suppressors in small-cell and transitional-cell carcinoma (TCC) arising concomitantly in 13 patients. Fourteen cases of pure TCC were also included in the analysis. We identified frequent methylation of RASSF1 and MGMT and infrequent methylation of MLH1 and DAPK1 in cases of concomitant TCC and SCBC. Similar rates of methylation were found in pure and concomitant histopathologies, with the exception of MGMT, which was much less frequently methylated in pure TCC. These findings suggest that SCBC and TCC have common origins, establish DNA methylation of some tumor suppressors as frequent occurrences in both histopathologies, and suggest that MGMT methylation may be an SCBC-specific epimutation. Modern Pathology (2008) 21, 355-362; doi:10.1038/modpathol.3801012; published online 11 January 2008Keywords: urinary bladder; small-cell carcinoma; DNA methylation; epigenetics DNA methylation-induced silencing of gene expression is now recognized as an important contributor in all stages of carcinogenesis. 1 Methylation of CpGdense regions, or CpG islands (CpGIs), associated with the first exons of many genes, serves to recruit transcriptional silencing machinery, including methyl-CpG-binding proteins, histone deacetylases and methyltransferases, and ATP-dependent chromatin-remodeling enzymes. 2,3 Silencing of key tumor and metastasis suppressors, 4,5 drug-metabolizing enzymes, 6 and DNA-repair proteins 7 is an event that contributes to carcinogenesis, acquisition of invasiveness and metastatic potential, angiogenesis, and therapy refractoriness. DNA methylation is a target for both therapeutic and biomarker purposes. 8 Importantly, the study of DNA methylation in clinical samples may provide useful and novel insights into the pathobiology of disease processes such as cancer.Transitional-cell carcinoma (TCC) arises from urothelium, which lines the bladder, as well as the renal pelvis, ureter, and portions of the urethra. Although infrequent in occurrence, small-cell bladder cancer (SCBC) may evolve or co-evolve from pre-existing TCC. 9 We hypothesized that DNA methylation of specific genes may underlie the pathogenesis of SCBC. In this study, we quantitatively analyzed the methylation status of RASSF1,

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Phase I-II Study of Paclitaxel, Cisplatin, and Gemcitabine in Advanced Transitional-Cell Carcinoma of the Urothelium

Abstract: This combination of paclitaxel, cisplatin, and gemcitabine is feasible and highly active in patients with advanced TCC of the urothelium. Further evaluation of this regimen in patients with TCC is warranted.

Cited by 187 publications

References 31 publications

Bladder Cancer in 2010: How Far have We Come?

Bladder Cancer in 2010: How Far have We Come?

Phase II multicentre study of docetaxel plus cisplatin in patients with advanced urothelial cancer

Hypermethylation of tumor-suppressor gene CpG islands in small-cell carcinoma of the urinary bladder

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