Urinary Bladder Cancer
Conditions
Brief summary
To evaluate the feasibility, safety, and pathological response of dose-dense neoadjuvant gemcitabine and cisplatin in patients with muscle-invasive bladder cancer, with the goal of improving tumor downstaging and optimizing outcomes before radical cystectomy.
Detailed description
Muscle-invasive bladder cancer (MIBC) poses a significant therapeutic challenge due to its high risk of progression and metastasis. Radical cystectomy remains the cornerstone of curative treatment; however, many patients relapse due to undetected micrometastases at diagnosis. To address this, neoadjuvant chemotherapy (NAC) with cisplatin-based combinations has been established as standard care, demonstrating improved pathological downstaging and survival outcomes compared to surgery alone (Yin et al., 2020; Necchi et al., 2017). Gemcitabine and cisplatin (GC) is widely favored in NAC because of its comparable efficacy to older regimens and a more favorable toxicity profile (Galsky et al., 2016). However, conventional schedules may be limited by treatment delays and incomplete cycles, often due to cumulative toxicities or patient frailty. Dose-dense chemotherapy-delivering the same drugs at shorter intervals with growth factor support-has been proposed to improve outcomes by intensifying dose intensity and reducing tumor repopulation between cycles (Zargar et al., 2018; Kulkarni et al., 2020). Evaluating dose-dense GC in the neoadjuvant setting aims to balance efficacy and tolerability, potentially increasing rates of complete pathological response and improving long-term survival. This protocol seeks to explore the feasibility, safety, and oncological benefit of this approach in patients with MIBC.
Interventions
Participants will receive neoadjuvant ddGC, consisting of gemcitabine and cisplatin administered at shortened intervals (e.g., gemcitabine 1200 mg/m² on days 1 and 8, fractionated cisplatin 35 mg/m² on day 1and 8, every 14 days) with appropriate growth factor support. A total of four cycles are planned before radical cystectomy.
Sponsors
Assiut University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Type of Study: Prospective, single-arm, interventional study evaluating the safety, feasibility, and pathological response of dose-dense neoadjuvant gemcitabine and cisplatin in muscle-invasive bladder cancer. 2.4. 2- Study Setting: Clinical Oncology department, Assiut University Hospitals 2.4. 3- Study subjects: 1. Inclusion criteria: * Histologically confirmed urothelial carcinoma of the bladder, clinical stage T2-T4a, N0-N1, M0. * Eligible and fit for cisplatin-based chemotherapy (e.g., creatinine clearance ≥ 60 mL/min). * Candidate for radical cystectomy after neoadjuvant treatment. * ECOG performance status 0-1. * Adequate bone marrow, liver, and renal function as per institutional standards. 2. Exclusion criteria: * Histology predominantly other than urothelial carcinoma (e.g., small cell, squamous cell ≥50%). * Clinical or radiological evidence of distant metastases (M1). * Prior systemic chemotherapy or radiotherapy for bladder cancer. * Signific
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed urothelial carcinoma of the bladder, clinical stage T2-T4a, N0-N1, M0. * Eligible and fit for cisplatin-based chemotherapy (e.g., creatinine clearance ≥ 60 mL/min). * Candidate for radical cystectomy after neoadjuvant treatment. * ECOG performance status 0-1. * Adequate bone marrow, liver, and renal function as per institutional standards.
Exclusion criteria
Histology predominantly other than urothelial carcinoma (e.g., small cell, squamous cell ≥50%). * Clinical or radiological evidence of distant metastases (M1). * Prior systemic chemotherapy or radiotherapy for bladder cancer. * Significant renal impairm ent (creatinine clearance \< 60 mL/min). * ECOG performance status ≥ 2. * Significant comorbidities contraindicating chemotherapy (e.g., uncontrolled cardiac disease, severe infection).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pathologic Complete Response (pT0N0) Rate | At the time of radical cystectomy (approximately 4-6 weeks after completion of neoadjuvant chemotherapy). | Proportion of participants with no residual invasive or non-invasive tumor in the bladder and no lymph node involvement (ypT0N0) at the time of radical cystectomy, as determined by histopathological examination of the surgical specimen. |
Countries
Egypt
Contacts
Primary ContactNehal Suliman, Assistant lecturer
Backup ContactDoaa Aly, Assistant professor
Outcome results
None listed