Efficacy of intravesical gemcitabine and docetaxel for non-muscle invasive urothelial bladder cancer: A review of current literature

OBJECTIVE@#To determine the efficacy of sequential intravesical Gemcitabine and Docetaxel (siGD) in patients with non-muscle invasive bladder cancer (NMIBC) in preventing disease recurrence after transurethral resection, as an alternative to BCG-naïve patients or to failed intravesical BCG therapy.@*METHODS@#An extensive literature search on the use of siGD for BCG-naïve or BCG-refractory NMIBC was done using the following terms: non-muscle invasive bladder cancer, intravesical Gemcitabine and Docetaxel. Search results were filtered to include all retrospective studies and randomized controlled trials reporting the oncological outcomes of siGD published over the last 5 years from the conception of this study. Information on the safety profile and adverse events related to therapy were also reported, if available.@*RESULTS@#The authors’ search yielded 8 retrospective articles describing the efficacy of siGD for NMIBC, 5 of which had complete and accessible English manuscripts. A total of 476 low to high-risk NMIBC patients were included in the 5 eligible studies, 31 (6.5%) of which were BCG-naïve, while the rest failed BCG therapy. The reported one and two-year success rates were 54-69% and 34-55%, respectively. The recurrence-free survival rates at 1 and 2 years were 49-60% and 29-46%, respectively. Bladder cancer-specific mortality at 1 and 2-years were 1-3% and 4-11%, respectively. Treatment-related adverse reactions were mostly mild, the most common of which were urinary frequency, urgency, hematuria, and dysuria.@*CONCLUSION@#Sequential intravesical Gemcitabine and Docetaxel is a feasible alternative for BCG-naïve and BCG-refractory NMIBC patients. Oncological outcomes are comparable to BCG therapy with less adverse effects.

Efficiency of prophylactic intravesical chemotherapy after nephroureterectomy for primary upper tract urothelial carcinoma / 中华泌尿外科杂志

Objective To explore the efficiency of prophylactic intravesical chemotherapy after nephroureterectomy for primary upper tract urothelial carcinoma.Methods Forty-seven patients with primary upper tract urothelial carcinoma who underwent nephroureterectomy were retrospectively analyzed.There were 25 male and 22 female patients with mean age of 68 years.Patients were divided into intravesical chemotherapy group (n =32) and non-intravesical chemotherapy group (n =15).In the intravesical chemotherapy group, there were 14 male and 18 female patients with mean age of 70.3 years;20 cases located at left side while 12 at the right side.In non-intravesical chemotherapy group, There were 11 male and 4 female patients with mean age of 65.0 years;10 cases located at left side while 5 at the right side.The age, gender, side of the two groups were not statistical different.The two groups were followed up, and the tumor stage, grade, recurrence rate, cancer-free survival time were compared.Results The pathology results of all cases were urothelial carcinoma.In the intravesical chemotherapy group, 23 cases were high grade tumors with 9 low grade tumors.There were 15 cases of Ta-T1 stage, 8 cases of T2 stage and 9 cases of T3 stage;the tumor of 19 cases located at pelvis, 12 located at ureter, 1 located at pelvis and ureter;the mean size of the tumors was (2.75 ± 1.49) cm;8 cases were multiple while 24 were single.In the non-intravesical chemotherapy group, 12 cases were high grade tumors with 3 low grade tumors, there were 6 cases of Ta-T1 stage, 4 cases of T2 stage and 5 cases of T3 stage;the tumor of 11 cases located at pelvis, 3 located at ureter, 1 located at pelvis and ureter;the mean size of the tumors was (3.11 ± 1.48) cm;6 cases were multiple while 9 were single.The items mentioned above did not reach statistical difference between the two groups(P ＞0.05).6 patients relapsed in intravesical chemotherapy group while 7 in non-intravesical chemotherapy group.The recurrence rate of bladder cancer of intravesical chemotherapy group was lower than that of non-intravesical chemotherapy group (18.75％ vs.46.67％, χ2 =3.978, P =0.046).Compared with non-intravesical chemotherapy group, intravesical chemotherapy group had longer cancer-free survival, but it did not reach statistical difference (36.5months vs.29.6months, t =1.079, P =0.286).The age and tumor grade were risk factors of bladder cancer recurrence, meanwhile the gender, tumor side, tumor stage, voided urine cytology, tumor size, and location were not.Conclusion Prophylactic intravesical chemotherapy after nephroureterectomy for primary upper tract urothelial carcinoma could reduce the recurrence rate of bladder cancer.

Research Progress in Intravesical Chemotherapy for Non-muscle-invasive Bladder Cancer / 中国药师

Bladder cancer is the most common malignant solid tumor in urinary system. More than 75% cases of bladder cancer have been diagnosed as non-muscle-invasive bladder cancer ( NMIBC ) . Transurethral resection of bladder tumor ( TURBT ) is the standard method for the diagnosis and treatment for bladder cancer, however, due to its problem of recurrence, adjuvant intravesical therapy with either immunotherapy or chemotherapy has been used to reduce recurrence and achieve better efficacy for the patients in appropriate stages. The review focused on current progress in chemotherapy agents, targeted bladder drug delivery systems and treat-ment strategies for NMIBC, which would provide guidance for clinical intravesical chemotherapy.

Correlation of the quality of life and lower urinary tract symptoms in patients under intravesical chemotherapy / 中华泌尿外科杂志

Objective To evaluate the quality of life (QoL) in patients undergone intravesical chemotherapy for non-muscle invasive bladder cancer and analyze the correlation of the quality of life and low urinary tract symptoms in this group of patients.Methods 31 male patients and 15 female patients were enrolled from Jan.2012 to Mar.2013.The average age was 54 (35-71) years.Questionnaires of QoL and core lower urinary tract symptom score (CLSS) were given to 46 patients before intravesical chemotherapy and the 1 st,6th month after starting the instillation.Before the instillation,the scores of QoL and CLSS were 55.7±6.2 and 6.5±2.1,respectively,the change of QoL and CLSS were compared to baseline,and then the correlation of the low urinary tract symptoms and quality of life was analyzed.Results At the end of 1st and 6th month,the QoL scores were 74.7±8.1 and 78.5± 10.6.The CLSS scores were 8.9±2.0 and 9.1 ± 1.8,respectively.The differences were significant (P ＜0.05) when compared to the baselines.The areas of working activity and free time were affected much more than other areas,and the scores increased from 8.3±2.1 and 19.2±5.7 to 14.3±5.6 and 23.7±4.2,respectively.The area of free time was found to be associated with local symptoms (r=0.61).Conclusions Intravesical treatment can impair the QoL of patients.Low urinary tract symptom is an important factor and is associated with impairment of QoL,suggesting the relief of local symptoms may improve the overall quality of life.

In vitro and in vivo studies of pirarubicin-loaded SWNT for the treatment of bladder cancer

Intravesical chemotherapy is an important part of the treatment for superficial bladder cancer. However, the response to it is limited and its side effects are extensive. Functional single-walled carbon nanotubes (SWNT) have shown promise for tumor-targeted accumulation and low toxicity. In the present study, we performed in vivo and in vitro investigations to determine whether SWNT-based drug delivery could induce high tumor depression in rat bladder cancer and could decrease the side effects of pirarubicin (tetrahydropyranyl-adriamycin, THP). We modified SWNT with phospholipid-branched polyethylene glycol and constructed an SWNT-THP conjugate via a cleavable ester bond. The cytotoxicity of SWNT-THP against the human bladder cancer cell line BIU-87 was evaluated in vitro. Rat bladder cancer in situ models constructed by N-methyl-N-nitrosourea intravesical installation (1 g/L, 2 mg/rat once every 2 weeks for 8 weeks) were used for in vivo evaluation of the cytotoxicity of SWNT and SWNT-THP. Specific side effects in the THP group including urinary frequency (N = 12), macroscopic hematuria (N = 1), and vomiting (N = 7) were identified; however, no side effects were observed with SWNT-THP treatment. Flow cytometry was used to assess the cytotoxicity in vitro and in vivo. Results showed that SWNT alone did not yield significant tumor depression compared to saline (1.74 ± 0.56 and 1.23 ± 0.42%) in vitro. SWNT-THP exhibited higher tumor depression than THP-saline in vitro (74.35 ± 2.56 and 51.24 ± 1.45%) and in vivo (52.46 ± 2.41 and 96.85 ± 0.85%). The present findings indicate that SWNT delivery of THP for the treatment of bladder cancer leads to minimal side effects without loss of therapeutic efficacy. Therefore, this nanotechnology may play a crucial role in the improvement of intravesical treatment of bladder cancer.

Intravesical Mitomycin C Instillation as a Prophylactic Treatment of Superficial Bladder Cancer / 대한비뇨기과학회지

Twenty one patients with multiple, large or recurrent superficial bladder cancer were treated with intravesical Mitomycin C instillation after TUR, and another 22 patients were treated with TUR alone The Mitomycin C group and control group were statistically identical in tumor size, grade, multiplicity and recurrences. Mean follow-up period were 13.9 months in Mitomycin C group and 23.2 months in controls. Recurrence rate was 42.9% in Mitomycin C group, and 40.9% in controls during the first 3 months and it was 66.7% and 68.2% respectively during the 12 months. Recurrences per 100 patient months was lO.1 and 9.6 respectively and the interval between the treatment and the first recurrence was 6.69 and 7.28 months respectively. Two of 21 patients in Mitomycin C group and 4 of 22 patients in controls had recurrent tumors with progression in stage during the follow-up period. There was no significant difference between the 2 groups. Therefore we can conclude that intravesical Mitomycin C instillation is not effective in the prophylaxis of tumor recurrence in the special group of patients with high risk of recurrence. This result is contrary to the several reports indicating marked reduction of recurrence by Mitomycin C. We discussed some factors which might influence to the 2 different outcome.

Prophylactic Effectiveness of Intravesical Mitomycin C Instillation to Prevent Recurrence of Superficial Bladder Carcinoma after Transurethral Resection / 대한비뇨기과학회지

Transurethral resection is the mainstay of curative treatment for superficial bladder cancer. Unfortunately, tumors recur in 40~70% of patients. Recently, we tried intravesical Mitomycin C chemotherapy after TUR to eliminate or decrease the frequency of recrrence. In this study, 22 patients with superficial bladder carcinoma received Mitomycin C intravesically at weekly intervals for eight weeks in dose of 40mg/40ml, starting about 48 hours after TUR. The results were compared to a group consists of 39 patients with superficial bladder cancer who received no further therapy after TUR. In the follow-up of 6 and 12 months, tumor recurrence was l3.6(3pts) and 18.2(4pts) percent respectively, in the Mitomycin C group, and 38.5(15pts, and 43.6(17 pts) per cent, respectively, in the control group. The frequency of recurrence in the Mitomycin C group was significantly less than that in the control group in the follow-up of both 6(P< 0.05) and 12 months(P< 0.05). Side effects of intravesical Mitomycin C therapy were negligibly minimal. Therefore, Mitomycin C intravesical chemotherapy after TUR is effective prophylactic treatment in reducing bladder tumor recurrence.

Prophylactic Intravesical Chemotherapy in Superficial Bladder Tumors / 대한비뇨기과학회지

Superficial bladder tumors are usually treated by TUR. However, recurrence of the tumor after complete resection occurs in about 50-70%, of the patients with a significant percentage of these recurrences showing a higher degree of malignancy. In 10% of the cases, the tumor progresses to invasive carcinoma. Most of these recurrent tumors will occur within 6-12 months. The multifocal nature of these tumors and the frequent recurrences after TUR indicate a need for adjuvant chemotherapy to reduce or delay the incidence of recurrence tumors. We studied to evaluate prophylactic effects of topical chemotherapy in 116 cases with superficial bladder tumors admitted to the Department of Urology, Keimyung University School of Medicine during the period from Jenuary, 1971 through July, 1985. All patients were followed up for more than 6 months. Study group consists of 83 cases (Thio-tepa: 39, Adriamycin; 44) treated with topical chemotherapy following TUR during the period from January, 1978 through July, 1985. Control group consists of 33 cases treated by TUR only during the period from January 1971 through December, 1977. Following results were obtained: 1. No. of patients with recurrence; In study group, 36Pr In control group. 67% 2. Average interval of recurrence: In study group, 38 months. In control group, 30 months 3. Recurrence rate; In study group, 2.58 In control group, 3.16 4. Complication: local side effects; In TUR + Thio-tepa, 20.5% In TUR + Adriamycin, 15.9%.

Intravesical Chemotherapy in Superficial Bladder Tumor: Preliminary Report / 대한비뇨기과학회지

We tried to treat 16 patients with superficial transitional cell carcinoma of the bladder with prophylactic and therapeutic intravesical chemotherapy. The 2 drugs used were adriamycin and thio-tepa and checked for efficacy by repeated cystoscopy with at least 3 months` interval. The clinical data and results of both groups are presented and the importance of intravesical treatment with minimal toxicity is discussed with a brief review of the literatures.

A Clinical Observation of the Intravesical Thiotepa in Bladder Cancer / 대한비뇨기과학회지

Primary transitional cell carcinoma of the bladder was treated with prophylactic and therapeutic Intravesical thiotepa in 7 cases. In 5 cases of stage A tumor, postoperative follow up was averaged 10.8 months and 4 cases were tumor free (80%). In 2 cases of infiltrating tumor, the instillation was not effective. Thiotepa can be given safely in the 7 days post-operative period and no leukopenia and bladder irritation symptoms were occurred.

Intravesical Chemotherpy in Superficial Transitional Cell Carcinoma of the Bladder Preliminary Report / 대한비뇨기과학회지

Eight patients with superficial stage O or A transitional cell carcinoma and 1 patient with infiltrating stage B2 or C transitional cell carcinoma of the bladder were treated with intravesical bleomycin sulfate every 5 or 7 Jays for 8 treatments. No hematologic, skin reaction and pulmonary fibrosis were observed in all patients. Doxorubicia hydrochloride was combined in 1 patient and definitive radiotherapy was added in the case with infiltrating transitional cell carcinoma, who was not a candidate for radical surgery. Follow-up cystoscopy and urine cytology should be done with at least 3 months interval in proof of effectiveness of intravesical chemotherapy. The possibility of obtaining even temporary regression and pronounced palliative effects or permanent cure using intravesical chemotherapy should not be underestimated and its clinical trial in superficial bladder tumor should be considered along with surgical therapy. General concept of intravesical chemotherapy is reviewed and discussed.