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Phase II trial of sequential gemcitabine Phase II trial of sequential gemcitabine and carboplatin followed by paclitaxel and carboplatin followed by paclitaxel
as first-line treatment of advanced as first-line treatment of advanced urothelial carcinomaurothelial carcinoma
Presented by Celine BOUTROSPresented by Celine BOUTROS
Hotel-Dieu de FranceHotel-Dieu de France
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BackgroundBackground
• Bladder cancer is the 4Bladder cancer is the 4thth cancer in men, the 9 cancer in men, the 9thth in women in women
• 69,000 new cases diagnosed in the US in 200869,000 new cases diagnosed in the US in 2008
• Transitional Cell Carcinoma (TCC): most frequent histological subtypeTransitional Cell Carcinoma (TCC): most frequent histological subtype
• The standard first-line regimen in advanced TCC:The standard first-line regimen in advanced TCC:
- 1989-2000: Methotrexate, Vinblastine, Doxorubicin, Cisplatin (MVAC)- 1989-2000: Methotrexate, Vinblastine, Doxorubicin, Cisplatin (MVAC)11
- > 2000: Gemcitabine plus Cisplatin- > 2000: Gemcitabine plus Cisplatin22 : similar activity, less toxicity : similar activity, less toxicity
1 Sternberg CN et al. Cancer 1989;64:2448-2458.2 Von der Maase H et al. J Clin Oncol 2000;18:3068-3077.
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Objectives of the studyObjectives of the study
• Explore the activity of Explore the activity of Gemcitabine plus Carboplatin Gemcitabine plus Carboplatin (GC) followed sequentially with (GC) followed sequentially with Paclitaxel in advanced TCC Paclitaxel in advanced TCC
Secondary Secondary objectiveobjective
Secondary Secondary objectiveobjective • Assess the toxicity profile of the Assess the toxicity profile of the
regimenregimen
Primary objectivePrimary objectivePrimary objectivePrimary objective
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Materials and MethodsMaterials and Methodseligibilityeligibility
Eligibility Criteria:Eligibility Criteria:
• At least one dimensionally measurable diseaseAt least one dimensionally measurable disease• Locally advanced or metastatic diseaseLocally advanced or metastatic disease• Histological infiltrative urothelial cancerHistological infiltrative urothelial cancer• No prior chemotherapy No prior chemotherapy unless given in more than one year free-unless given in more than one year free-intervalinterval• No prior radiation therapyNo prior radiation therapy• Performance status (PS) ≤ 2Performance status (PS) ≤ 2• Adequate blood counts and chemistriesAdequate blood counts and chemistries• Normal organ functionNormal organ function
Eligibility Criteria:Eligibility Criteria:
• At least one dimensionally measurable diseaseAt least one dimensionally measurable disease• Locally advanced or metastatic diseaseLocally advanced or metastatic disease• Histological infiltrative urothelial cancerHistological infiltrative urothelial cancer• No prior chemotherapy No prior chemotherapy unless given in more than one year free-unless given in more than one year free-intervalinterval• No prior radiation therapyNo prior radiation therapy• Performance status (PS) ≤ 2Performance status (PS) ≤ 2• Adequate blood counts and chemistriesAdequate blood counts and chemistries• Normal organ functionNormal organ function
Single-Arm, Multicenter, Phase II trial , from September 2004 to September 2007
Single-Arm, Multicenter, Phase II trial , from September 2004 to September 2007
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Materials and MethodsMaterials and Methodstreatmenttreatment scheduleschedule
Evaluation(RECIST)Evaluation(RECIST)
Gemcitabine Gemcitabine 800mg/m800mg/m2 2 (D1, D8) (D1, D8)
++Carboplatin AUC 2Carboplatin AUC 2
(D1, D8)(D1, D8)
Every 3 weeks for Every 3 weeks for 4 cycles4 cycles
Gemcitabine Gemcitabine 800mg/m800mg/m2 2 (D1, D8) (D1, D8)
++Carboplatin AUC 2Carboplatin AUC 2
(D1, D8)(D1, D8)
Every 3 weeks for Every 3 weeks for 4 cycles4 cycles
Paclitaxel Paclitaxel 60 mg/m60 mg/m22
weekly for 12 weekly for 12 weeksweeks
Paclitaxel Paclitaxel 60 mg/m60 mg/m22
weekly for 12 weekly for 12 weeksweeks
Evaluation(RECIST)Evaluation(RECIST)
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ResultsResultsPatient CharacteristicsPatient Characteristics
nn %%
Mean age (years)Mean age (years) 6868
Male / FemaleMale / Female 22 / 5 22 / 5 81/1881/18
ECOG PS ≤ 2ECOG PS ≤ 2 27 27 100100
Prior radical cystectomyPrior radical cystectomy 12 12 4444
Prior chemotherapyPrior chemotherapy 0 0 00
Distant metastasesDistant metastases 11 11 4040
Locoregional disease with only Locoregional disease with only positive lymph nodes positive lymph nodes 16 16 6060
Patients included Patients included 2727
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ResultsResultsDrug deliveryDrug delivery
GC sequenceGC sequencePaclitaxel Paclitaxel sequencesequence
Mean number of Mean number of cycles administeredcycles administered 3.53.5 77
Number of patients Number of patients removedremoved
-- progressionprogression
- personal request- personal request
77
66
11
66
00
66
Dose reduction for Dose reduction for myelosuppressionmyelosuppression 22 22
Assessment of drug delivery for GC and Paclitaxel Assessment of drug delivery for GC and Paclitaxel sequencessequences
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ResultsResultsTreatment efficacyTreatment efficacy
GC sequenceGC sequence End of therapyEnd of therapy
Overall response rateOverall response rateCRCRPRPR
41% 41% (1)(1)
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1010
43% 43% (2)(2)
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SD SD 33 44
PDPD 1111 44
Response Assessment to GC and Paclitaxel Response Assessment to GC and Paclitaxel sequences sequences
(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)
ResultsResultsfollow-upfollow-up
• Median response duration: 6 monthsMedian response duration: 6 months
• Median follow-up: 7 monthsMedian follow-up: 7 months
- 21 patients died- 21 patients died
- 6 remained alive ---> 2 CR- 6 remained alive ---> 2 CR
---> 1 PR---> 1 PR
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ResultsResultstreatment-relatedtreatment-related toxicities (grade 3/4)toxicities (grade 3/4)
GC sequenceGC sequence End of treatmentEnd of treatment
NeutropeniaNeutropenia 22 00
AnemiaAnemia 33 11
ThrombocytopeniaThrombocytopenia 22 00
Nausea/emesisNausea/emesis 11 00
DiarrheaDiarrhea 00 11
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ResultsResultsMyelosuppression-related complicationsMyelosuppression-related complications
GC sequenceGC sequence End of treatmentEnd of treatment
Febrile neutropeniaFebrile neutropenia 11 0
Platelet transfusionPlatelet transfusion 11 0
RBC transfusionRBC transfusion 1111 0
Bleeding episodesBleeding episodes 00 0
ConclusionConclusion
• Well tolerated regimenWell tolerated regimen
• ORR is in agreement with the results of ORR is in agreement with the results of previous regimensprevious regimens
• Limited number of patientsLimited number of patients
• Relatively short follow-up (7 months)Relatively short follow-up (7 months)
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