Intravesical Gemcitabine Therapy for Superficial Transitional Cell Carcinoma of the Bladder: A Phase I and Pharmacokinetic Study

2003 ◽  
Vol 21 (4) ◽  
pp. 697-703 ◽  
Author(s):  
Menachem Laufer ◽  
Sakkaraiappan Ramalingam ◽  
Mark P. Schoenberg ◽  
Mary Ellen Haisfield-Wolf ◽  
Eleanor G. Zuhowski ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Superficial Bladder Cancer ◽  
Transitional Cell ◽  
Maximum Tolerated Dose ◽  
Intravesical Therapy ◽  
Systemic Absorption ◽  
Therapy Failure ◽  
Low Concentrations ◽  
Transitional Cell Bladder Carcinoma ◽  
Carcinoma Of The Bladder

Purpose: To determine maximum-tolerated dose, toxicities, and pharmacokinetics associated with weekly intravesical gemcitabine therapy in patients with superficial bladder cancer. Patients and Methods: Fifteen patients with recurrent superficial transitional cell bladder carcinoma who experienced prior intravesical therapy failure were studied. Two to 4 weeks after complete transurethral resection, gemcitabine was administered intravesically, once weekly for 6 consecutive weeks. Dwell time was 2 hours. Pharmacokinetics of gemcitabine and its metabolite, 2′2′-difluorodeoxyuridine (dFdU), were studied in plasma and urine. Cystoscopy was repeated 6 weeks after therapy. Results: Three-patient cohorts were enrolled sequentially at doses of 500, 1,000, and 1,500 mg in 100 mL 0.9% NaCl. Two patients received 2,000 mg in 100 mL. An additional four patients received 2,000 mg in 50 mL. No grade 4 toxicity or clinically relevant myelosuppression was noted. Nine of 13 evaluable patients were recurrence-free at 12 weeks. Low concentrations of gemcitabine (≤ 1 μg/mL) were present transiently in plasma of all patients receiving 2,000 mg in 50 mL. Gemcitabine was undetectable in plasma of other patients. dFdU was undetectable in plasma of patients receiving less than 1,500 mg. At doses ≥ 1,500 mg, dFdU concentrations increased until 90 to 120 minutes and then declined little, if any. Plasma dFdU concentrations implied absorption of 0.5% to 5.5% of instilled dose. Between 61% and 100% of the gemcitabine dose was accounted for in voided urine. No dFdU was measured in voided urine. Conclusion: Intravesical gemcitabine, at doses up to 2 g/wk, is well tolerated, is associated with minimal systemic absorption, and has promising efficacy in treatment of superficial bladder cancer.

Phase I Trial of Intravesical Docetaxel in the Management of Superficial Bladder Cancer Refractory to Standard Intravesical Therapy

2006 ◽  
Vol 24 (19) ◽  
pp. 3075-3080 ◽  
Author(s):  
James M. McKiernan ◽  
Puneet Masson ◽  
Alana M. Murphy ◽  
Manlio Goetzl ◽  
Carl A. Olsson ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Phase I ◽  
Phase I Trial ◽  
Superficial Bladder Cancer ◽  
Transitional Cell ◽  
Maximum Tolerated Dose ◽  
Intravesical Therapy ◽  
Systemic Absorption ◽  
Microtubule Depolymerization ◽  
Grade 3

Purpose Up to 50% of patients treated with intravesical agents for superficial bladder cancer will experience recurrence. Response rates to second-line intravesical therapies range from 20% to 40%. For these high-risk patients, novel agents are necessary to prevent recurrence. Docetaxel is a microtubule depolymerization inhibitor with unique physiochemical properties, making it an excellent candidate for investigation as an intravesical agent. Patients and Methods This phase I trial included patients with recurrent Ta, T1, and Tis transitional cell carcinoma who experienced treatment failure with at least one prior intravesical treatment. Docetaxel was administered as six weekly instillations at a starting dose of 5 mg, with a dose-escalation model used until a maximum tolerated dose (MTD) was achieved. Primary end points were dose-limiting toxicity (DLT) and MTD. Efficacy was evaluated by cystoscopy with biopsy, cytology, and computed tomography imaging. Results Eighteen patients (100%) completed the trial, and the distribution of stages included six patients with Tis, seven with Ta, and five with T1 disease. No grade 3 or 4 DLTs occurred in 108 infusions, and no patient had systemic absorption of docetaxel. Eight (44%) of 18 patients experienced grade 1 or 2 toxicities, with dysuria being the most common. Ten (56%) of 18 patients had no evidence of disease at their post-treatment cystoscopy and biopsy. None of the patients who experienced relapse had disease progression. Conclusion Intravesical docetaxel exhibited minimal toxicity and no systemic absorption in the first human intravesical clinical trial. This suggests that docetaxel is a safe agent for further evaluation of efficacy in a phase II trial.

A combined phase I/II trial of intravesical nanoparticle albumin-bound paclitaxel in the treatment of refractory non–muscle- invasive transitional cell bladder cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e16047-e16047
Author(s):  
L. Barlow ◽  
M. Laudano ◽  
M. Mann ◽  
M. Desai ◽  
D. Petrylak ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Phase I ◽  
Dose Escalation ◽  
Phase I Trial ◽  
Transitional Cell ◽  
Intravesical Therapy ◽  
Systemic Absorption ◽  
Imaging Results ◽  
Muscle Invasive ◽  
Ongoing Phase

e16047 Background: Up to 50% of patients treated with intravesical agents for non-muscle-invasive bladder cancer will recur. Response rates to current second line intravesical therapies average less than 20%. For these high risk patients, novel agents are necessary. Our previously completed phase I trial showed docetaxel to be a safe and efficacious agent for intravesical therapy. Nanoparticle albumin-bound (nab-) paclitaxel has been shown to have increased solubility and lower toxicity compared to docetaxel in systemic therapy and is therefore an appropriate candidate for further investigation as an intravesical agent. Methods: The ongoing phase I component of this combined phase I/II trial began enrollment on 1/1/08 and has reached 72% accrual as of 1/1/09. Inclusion criteria include recurrent high grade (HG) Ta, T1 and Tis transitional cell carcinoma failing at least one prior regimen with any intravesical agent. In phase I, 6 weekly instillations of nab-paclitaxel were administered beginning at a dose of 150 mg with a dose escalation model used until a maximal tolerated dose (MTD) was achieved. The primary endpoints were dose- limiting toxicity (DLT) and MTD; the secondary endpoint was response rate. Efficacy was evaluated by cystoscopy with biopsy, cytology, and CT imaging. Results: 13/18 patients have enrolled in this phase I trial to date, and the distribution of stages included 5 patients with Tis, 4 patients with HGTa, and 4 patients with HGT1. No patient has had any systemic absorption of nab-paclitaxel as measured by HPLC assays, and no grade 3 or 4 DLT has been encountered. Fifty-four percent (7/13) patients were noted to experience grade 1 toxicities, with dysuria being the most common. Forty-two percent (5/12) of completed patients had no evidence of disease at their post-treatment cystoscopy. None of the patients who developed recurrent disease have had disease progression. Conclusions: Intravesical nab-paclitaxel has exhibited minimal toxicity and no systemic absorption in the first ever human intravesical dose escalation trial. Upon completion of this ongoing phase I trial, we plan to evaluate this agent in a larger phase II efficacy study. No significant financial relationships to disclose.

Superficial bladder cancer: the primacy of grade in the development of invasive disease.

1987 ◽  
Vol 5 (1) ◽  
pp. 125-130 ◽  
Author(s):  
F M Torti ◽  
B L Lum ◽  
D Aston ◽  
N MacKenzie ◽  
M Faysel ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Logistic Regression ◽  
Superficial Bladder Cancer ◽  
Medical Center ◽  
Bladder Wall ◽  
Transitional Cell ◽  
Invasive Disease ◽  
Deep Muscle ◽  
Carcinoma Of The Bladder ◽  
Muscle Invasion

Tumor characteristics thought to predict for development of deep muscle invasion after resection of superficial bladder cancer were retrospectively analyzed in 252 patients with transitional cell carcinoma of the bladder at Stanford University Medical Center. Stage 0 patients accounted for 190 of the patient population (75.5%), while stage A and B1 comprised 51 (20%) and 11 (4.5%), respectively. The median follow-up time was 62 months. Forty-three patients subsequently developed deep muscle invasion; these included 24 (12.6%), 14 (27.5%), and 5 (45.5%) of stage 0, A, and B1 patients (P = .002), or 15 (10%), 15 (9%), and 13 (33%) of grade 1, 2, and 3 tumors (P = .001), respectively. When analyzed by univariate logistic regression, grade (P = .0001) and stage (P = .0118) were significant predictors for invasive disease. Site of tumor and number of tumors at presentation were not significant factors for invasion deep into the bladder wall. When multiple logistic regression was performed, only grade remained as a significant tumor variable to predict for invasive disease (P less than .0091). Risk of invasive disease did not appear to increase with increasing number of recurrences, remaining at approximately an 11% invasion rate through 12 recurrences. In this analysis, grade was the most significant tumor variable in superficial bladder cancer predicting for the development of invasive carcinoma. Future clinical trials for definitive or adjuvant therapy of this disease must stratify for this variable.

scholarly journals Disseminated BCG: Complications of Intravesical Bladder Cancer Treatment

2014 ◽  
Vol 2014 ◽  
pp. 1-3 ◽  
Author(s):  
Uyen To ◽  
Joyce Kim ◽  
David Chia
Keyword(s):  
Bladder Cancer ◽  
Hypersensitivity Pneumonitis ◽  
Superficial Bladder Cancer ◽  
Transitional Cell ◽  
Low Grade ◽  
Newly Diagnosed ◽  
Insidious Onset ◽  
Initial Symptoms ◽  
Intravesical Bcg ◽  
Carcinoma Of The Bladder

Intravesical bacillus Calmette-Guerin (BCG) has been established as an effective treatment of superficial bladder cancer (Parker and Kommu, 2013). However, major side effects, including pneumonitis, sepsis, and even death, may occur in <5% of patients (Gonzalez et al., 2003). Here we present a case of severe disseminatedMycobacterium bovisfollowing intravesical BCG administration. Our patient is a 76-year-old gentleman with newly diagnosed superficial transitional cell carcinoma of the bladder who recently received his first intravesical BCG treatment. He initially presented with hemoptysis and was found to have extensive patchy infiltrates bilaterally. He was treated for pneumonia with antibiotics and then with steroids for hypersensitivity pneumonitis but continued to deteriorate. Due to the temporal proximity of his exposure to BCG, we administered treatment for presumed disseminated BCG infection with rifampin, isoniazid, and ethambutol. Within a 48-hour period, the patient improved dramatically. The reported cases of infection from intravesical BCG illustrate an insidious onset with initial symptoms of low-grade fevers and cystitis but may progress to pneumonitis. If the symptoms persist for more than 7 days or if there is clinical deterioration, RIPE therapy (with rifampin, isoniazid, pyridoxine, and ethambutol) and a fluoroquinolone should be administered for a 6–9-month course along with steroids for 4–6 weeks (Naudžiunas et al., 2012).

scholarly journals Current Concepts in Biomarker Technology for Bladder Cancers

2000 ◽  
Vol 46 (5) ◽  
pp. 595-605 ◽  
Author(s):  
Martin Burchardt ◽  
Tatjana Burchardt ◽  
Ahmad Shabsigh ◽  
Alexandre De La Taille ◽  
Mitchell C Benson ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Matrix Protein ◽  
Transitional Cell ◽  
High Sensitivity ◽  
Diagnostic Techniques ◽  
Single Marker ◽  
Cell Cycle Regulatory Proteins ◽  
Standard Of Practice ◽  
Carcinoma Of The Bladder ◽  
Potential Biomarkers

Abstract Background: Transitional cell carcinoma of the bladder (TCC) is the second most common malignancy of the urinary tract. More than 70% of treated tumors recur, and 30% of recurrent tumors progress. Currently, pathologic staging and grading are valuable prognostic factors for detecting and monitoring TCC. Urinalysis, cystoscopy, and cytology are either invasive or lack sensitivity and specificity. The availability of a noninvasive, reliable, and simple test would greatly improve the detection and monitoring of patients with TCC. Several biomarkers for bladder cancer have been proposed, but no single marker has emerged as the test of choice. Approach: We undertook a comprehensive literature search using Medline to identify all publications from 1980 to 1999. Articles that discussed potential biomarkers for TCC were screened. Only compounds that demonstrated high sensitivity or specificity, significant correlation with TCC diagnosis and staging, and extensive investigation were included in this review. Content: Potential biomarkers of disease progression and prognosis include nuclear matrix protein, fibrin/fibrinogen product, bladder tumor antigen, blood group-related antigens, tumor-associated antigens, proliferating antigens, oncogenes, growth factors, cell adhesion molecules, and cell cycle regulatory proteins. The properties of the biomarkers and the methods for detecting or quantifying them are presented. Their sensitivities and specificities for detecting and monitoring disease were 54–100% and 61–97%, respectively, compared with 20–40% and 90% for urinalysis and cytology. Summary: Although urine cytology and cystoscopy are still the standard of practice, many candidate biomarkers for TCC are emerging and being adopted into clinical practice. Further research and better understanding of the biology of bladder cancer, improved diagnostic techniques, and standardized interpretation are essential steps to develop reliable biomarkers. It is possible that using the current biomarkers as an adjuvant modality will improve our ability to diagnose and monitor bladder cancer.

Superficial Bladder Cancer Therapy: A Review

2005 ◽  
Vol 72 (3) ◽  
pp. 307-317
Author(s):  
P.F. Bassi ◽  
V. Serretta ◽  
F. Pinto ◽  
A. Calpista ◽  
A. Galuffo ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Transurethral Resection ◽  
Superficial Bladder Cancer ◽  
Risk Groups ◽  
Tumor Stage ◽  
Intravesical Therapy ◽  
Size Number ◽  
Muscle Invasion ◽  
Prevention Of Recurrence

Most bladder cancers present as a superficial disease, confined to the bladder mucosa or submucosal layer, without muscle invasion. Most superficial tumors have a propensity for recurrence after transurethral resection; some have a high risk for progression to muscle invasion. The treatment aim in superficial bladder cancer with intravesical therapy is three-fold: (1) eradicate existing disease, (2) prevention of recurrence, (3) prevention of tumor progression. The prognostic factors (tumor stage, grade, size, number and recurrence pattern) allow the stratification of tumors in different risk groups to plan treatment. Studies on pharmacokinetics have proved the efficacy of optimized drug delivery. Comparing resection with and without intravesical chemotherapy, a short-term reduction, approximately 15%, in tumor recurrence with chemotherapy can be obtained, but no effect on progression was proven. No agent has proved to be more effective than the others. A single instillation of chemotherapy immediately after transurethral resection has proven to be effective, but the role of maintenance therapy is controversial. Immunotherapy, in the form of Bacillus Calmette-Guerin, is generally shown to be more effective than chemotherapy, even if the results in comparison to mitomycin C do not result conclusive. Several new approaches are being explored to improve the efficacy of this therapy.

The Possible Influence of Antibiotics on Results of Bacillus Calmette-Guérin Intravesical Therapy for Superficial Bladder Cancer

1991 ◽  
Vol 146 (2 Part 1) ◽  
pp. 444-446 ◽  
Author(s):  
Ad P.M. Van Der Meijden ◽  
Bert Van Klingeren ◽  
Peter A. Steerenberg ◽  
Liesbeth C. De Boer ◽  
Wim H. De Jong ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Superficial Bladder Cancer ◽  
Intravesical Therapy ◽  
Bacillus Calmette Guerin

Evaluation of DD23 as a marker for detection of recurrent transitional cell carcinoma of the bladder in patients with a history of bladder cancer

Urology ◽  
2003 ◽  
Vol 61 (3) ◽  
pp. 539-543 ◽  
Author(s):  
Scott M Gilbert ◽  
Robert W Veltri ◽  
Alex Sawczuk ◽  
Ahmad Shabsigh ◽  
David R Knowles ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Transitional Cell Carcinoma ◽  
Cell Carcinoma ◽  
Transitional Cell ◽  
History Of ◽  
Carcinoma Of The Bladder
Sign in / Sign up

Export Citation Format

Share Document