Phase II trial of sequential gemcitabine and carboplatin followed by paclitaxel as firstline treatme

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Phase II trial of sequential gemcitabine and
carboplatin followed by paclitaxel as first-line
treatment of advanced urothelial carcinoma

• Presented by Celine BOUTROS
• Hotel-Dieu de France

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Background

• Bladder cancer is the 4th cancer in men, the 9th
  in women
• 69,000 new cases diagnosed in the US in 2008
• Transitional Cell Carcinoma (TCC) most frequent
  histological subtype
• The standard first-line regimen in advanced TCC
• - 1989-2000 Methotrexate, Vinblastine,
  Doxorubicin, Cisplatin (MVAC)1
• - gt 2000 Gemcitabine plus Cisplatin2
  similar activity, less toxicity

1 Sternberg CN et al. Cancer 1989642448-2458.
2 Von der Maase H et al. J Clin Oncol
2000183068-3077.
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Objectives of the study
Primary objective

• Explore the activity of Gemcitabine plus
  Carboplatin (GC) followed sequentially with
  Paclitaxel in advanced TCC

Secondary objective

• Assess the toxicity profile of the regimen

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Materials and Methodseligibility
Single-Arm, Multicenter, Phase II trial , from
September 2004 to September 2007

• Eligibility Criteria
• At least one dimensionally measurable disease
• Locally advanced or metastatic disease
• Histological infiltrative urothelial cancer
• No prior chemotherapy unless given in more than
  one year free-interval
• No prior radiation therapy
• Performance status (PS) 2
• Adequate blood counts and chemistries
• Normal organ function

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Materials and Methodstreatment schedule
Gemcitabine 800mg/m2 (D1, D8) Carboplatin AUC
2 (D1, D8) Every 3 weeks for 4 cycles
Paclitaxel 60 mg/m2 weekly for 12 weeks

Evaluation (RECIST)
Evaluation (RECIST)


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ResultsPatient Characteristics

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ResultsDrug delivery
Assessment of drug delivery for GC and Paclitaxel
sequences

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ResultsTreatment efficacy
Response Assessment to GC and Paclitaxel
sequences

• 8 responses of 11 achieved in locally advanced
  TCC without distant metastases
• Responses achieved in locally advanced TCC
  without distant metastases (same patients)

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Resultsfollow-up

• Median response duration 6 months
• Median follow-up 7 months
• - 21 patients died
• - 6 remained alive ---gt 2 CR
• ---gt 1 PR

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Resultstreatment-related toxicities (grade 3/4)
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ResultsMyelosuppression-related complications
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Conclusion

• Well tolerated regimen
• ORR is in agreement with the results of previous
  regimens
• Limited number of patients
• Relatively short follow-up (7 months)