Download Pre-specified Adverse Events: Cardiovascular

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
1
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
- > 2000: Gemcitabine plus Cisplatin2 : similar activity, less toxicity
1
2
Sternberg CN et al. Cancer 1989;64:2448-2458.
Von der Maase H et al. J Clin Oncol 2000;18:3068-3077.
2
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
3
Materials and Methods
eligibility
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 freeinterval
• No prior radiation therapy
• Performance status (PS) ≤ 2
• Adequate blood counts and chemistries
• Normal organ function
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Materials and Methods
treatment schedule
Gemcitabine
800mg/m2 (D1, D8)
+
Carboplatin AUC 2
(D1, D8)
Evaluation
(RECIST)
Paclitaxel
60 mg/m2
weekly for 12
weeks
Evaluation
(RECIST)
Every 3 weeks for
4 cycles
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Results
Patient Characteristics
n
Mean age (years)
%
68
Male / Female
22 / 5
81/18
ECOG PS ≤ 2
27
100
Prior radical cystectomy
12
44
Prior chemotherapy
0
0
Distant metastases
11
40
Locoregional disease with only
positive lymph nodes
16
60
Patients included
27
6
Results
Drug delivery
Assessment of drug delivery for GC and Paclitaxel
sequences
Paclitaxel
GC sequence
sequence
Mean number of
cycles administered
3.5
7
Number of patients
removed
7
6
- progression
- personal request
6
1
0
6
Dose reduction for
myelosuppression
2
2
7
Results
Treatment efficacy
Response Assessment to GC and Paclitaxel
sequences
GC sequence
End of therapy
41% (1)
43% (2)
1
10
3
3
SD
3
4
PD
11
4
Overall response rate
CR
PR
(1) 8 responses of 11 achieved in locally advanced TCC without distant metastases
(2) Responses achieved in locally advanced TCC without distant metastases (same patients)
8
Results
follow-up
•
•
Median response duration: 6 months
Median follow-up: 7 months
- 21 patients died
- 6 remained alive ---> 2 CR
---> 1 PR
9
Results
treatment-related toxicities (grade 3/4)
GC sequence
End of treatment
Neutropenia
2
0
Anemia
3
1
Thrombocytopenia
2
0
Nausea/emesis
1
0
Diarrhea
0
1
10
Results
Myelosuppression-related complications
GC sequence
End of treatment
Febrile neutropenia
1
0
Platelet transfusion
1
0
RBC transfusion
11
0
Bleeding episodes
0
0
11
Conclusion
•
•
•
•
Well tolerated regimen
ORR is in agreement with the results of
previous regimens
Limited number of patients
Relatively short follow-up (7 months)
12