5-aminolevulinic-acid-hexyl-ester and Carcinoma

To describe drugs used in bladder carcinoma.. Pubmed search for efficacy, mode of action and side effects for each molecule. Additional data were searched from the French regulatory agencies web sites (HAS and ANSM).. The drugs used in the treatment of bladder cancer are represented by the products referred to diagnosis (hexyl aminolevulinate), the intravesical instillations for the treatment of tumors not infiltrating the muscle and the infiltrating tumor chemotherapy (neo-adjuvant treatment or metastatic tumors). The hexyl aminolevulinate cystoscopy allows to identify a significantly greater number of lesions, including carcinoma in situ, compared to conventional white light cystoscopy. For intravesical instillations, BCG has a superior efficacy to mitomycin C with a lower tolerance. The chemotherapies for invasive tumors are effective in metastatic disease in 15-20% of cases with a mean survival of 12 to 14 months.. Except the use of hexyl aminolevulinate for improving the diagnosis, there was no emergence in recent years of new drugs for the treatment of bladder cancer. Targeted therapies currently available for many neoplasms were ineffective for bladder cancer.

Topics: Aminolevulinic Acid; Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; BCG Vaccine; Carcinoma; Cisplatin; Cystoscopy; Deoxycytidine; Doxorubicin; Fluorescence; Gemcitabine; Humans; Methotrexate; Mitomycin; Photosensitizing Agents; Urinary Bladder Neoplasms; Vinblastine

Photodynamic diagnosis and white-light TURB with adjuvant intravesical chemotherapy (ICT) is widely used in treatment of bladder cancer. This non-inferiority trial is designed to demonstrate non-inferiority regarding recurrence-free survival (RFS) of Hexvix. Non-inferiority of Hexvix

Topics: Administration, Intravesical; Adult; Aged; Aged, 80 and over; Aminolevulinic Acid; Antineoplastic Agents; Carcinoma; Chemotherapy, Adjuvant; Cystectomy; Cystoscopy; Disease-Free Survival; Female; Humans; Male; Middle Aged; Mitomycin; Photochemotherapy; Photosensitizing Agents; Prospective Studies; Urinary Bladder Neoplasms

To compare the recurrence of non-muscle invasive bladder carcinoma (NMIBC) after transurethral resection employing cystoscopy with hexaminolevulinate-based photodynamic diagnosis (PDD) or with standard white light.. We included patients with newly suspected NMIBC in this retrospective cohort study and compared those undergoing transurethral resection by white light cystoscopy (WLC) (2008-2010) and PDD (2010-2012). All patients were treated following established criteria for good quality resection. The primary outcome was the difference in the recurrence rate after 60 months' follow-up, but we also stratified recurrence by risk groups, as set by the European Organization for Research and Treatment of Cancer. The mean recurrence-free survival was compared between the cohorts. Odds ratios or hazard ratios are reported with their 95% confidence intervals.. The WLC and PDD cohorts comprised 124 and 91 subjects, respectively. There were no significant differences in recurrence rates between the cohorts at 6 months (recurrence rate 9/123; 7.3%), 12 months (17/118; 14.4%) or 60 months (39/102; 38.2%), with odds ratios of 1.23 (CI 0.48-3.25), 1.32 (CI 0.67-2.62) and 1.12 (CI 0.70-1.79), in favour of WLC, respectively. Further analysis showed no significant effect of PDD on either recurrence by risk group or on mean recurrence-free survival (hazard ratio, 1.12 [CI 0.70-1.79]).. We found no relevant differences in the recurrence of NMIBC after the introduction of PDD with hexaminolevulinate compared to standard WLC when used for transurethral resection in our single institution.

Topics: Aminolevulinic Acid; Carcinoma; Cystoscopy; Humans; Neoplasm Recurrence, Local; Retrospective Studies; Urinary Bladder; Urinary Bladder Neoplasms

Photodynamic diagnosis using hexaminolevulinate (HAL)-guided BL-TURB may reduce the recurrence risk in non-muscle invasive BCa compared to standard WL-TURB due to more sensitive tumor detection. The impact of the initial use of WL- vs. BL-TURB on follow-up costs was evaluated in this real-world data analysis.. Anonymous claims data of German statutory health insurances (GKV) from 2011 to 2016 were analyzed in a primary and adjusted study population. Selection criteria included five quarters before enrolment, one index quarter (InQ) of initial TURB and BCa diagnosis, either within two years for the primary analysis or within four years for the adjusted analysis, and a follow-up period (FU) of either eleven or three quarters, respectively.. In the primary analysis (n = 2331), cystectomy was identified as an important cost driver masking potential differences between cohorts. Therefore, patients undergoing cystectomy (InQ + FU) were excluded from the adjusted study population of n = 4541 patients (WL: 79%; BL: 21%). Mean total costs of BL-TURB were initially comparable to WL-TURB (WL: EUR 4534 vs. BL: EUR 4543) and tended to be lower compared to WL-TURB in the first two quarters of FU. After one year (3rd FU quarter), costs equalized. Considering total FU, mean costs of BL-TURB were significantly lower compared to WL-TURB (WL: EUR 7073 vs BL: EUR 6431; p = 0.045).. This retrospective analysis of healthcare claims data highlights the comparability of costs between BL-TURB and WL-TURB.

Topics: Aged; Aminolevulinic Acid; Carcinoma; Cystectomy; Cystoscopy; Female; Germany; Health Care Costs; Health Services Research; Humans; Insurance Claim Review; Male; Neoplasm Recurrence, Local; Photosensitizing Agents; Retrospective Studies; Urinary Bladder Neoplasms

Hexaminolevulinate hydrochloride with blue light cystoscopy is approved by the U.S. Food and Drug Administration as an adjunct to white light cystoscopy for the detection of urothelial cell carcinoma. In this study we examined the tolerability of the repeat use of white light cystoscopy with blue light cystoscopy.. We retrospectively reviewed the records of all patients who underwent white light cystoscopy with blue light cystoscopy using hexaminolevulinate hydrochloride during a 34-month period at 2 institutions. We compared the incidence of adverse events after initial and subsequent procedures. We grouped, graded and assigned the degree of attribution for all adverse events.. A total of 180 patients underwent 269 white light cystoscopy with blue light cystoscopy procedures. Of those 180 patients 118 (65%) underwent white light cystoscopy with blue light cystoscopy only 1 time. The other 62 (35%) patients underwent white light cystoscopy with blue light cystoscopy 2 or more times, including 43 (24%) 2 times and 19 (10%) 3 or more times. We noted 89 adverse events out of 269 procedures (33%), of which 66 (74%) occurred after the first white light cystoscopy with blue light cystoscopy; 14 (16%) after the second time and 9 (10%) after the third time or more. We found no statistically significant difference in adverse events between those patients undergoing 1 vs 2 or more white light cystoscopy with blue light cystoscopy procedures (p=0.134). We observed 1 grade 3 adverse event and no grade 4 or 5 adverse events. None of the adverse events were classified as probably or definitely related to hexaminolevulinate hydrochloride.. In this retrospective study we found no statistically significant difference in the frequency or the grade of adverse events between first and repeat use of white light cystoscopy with blue light cystoscopy using hexaminolevulinate hydrochloride.

Topics: Adult; Aged; Aged, 80 and over; Aminolevulinic Acid; Carcinoma; Cystoscopy; Female; Humans; Male; Middle Aged; Photosensitizing Agents; Retrospective Studies; Urinary Bladder Neoplasms; Urothelium

To assess the learning curve for fluorescence cystoscopy using hexaminolevulinate hydrochloride (HAL) in patients with bladder cancer.. Fifty patients underwent bladder instillation with HAL. Two senior residents inspected separately the bladder using white light cystoscopy, followed by fluorescence cystoscopy and mapped the lesions. An experienced with photodynamic diagnosis (PDD) urologist also performed both cystoscopies, mapped, resected or cold biopsied suspect lesions under the supervision of another experienced urologist. To evaluate the learning curve, patients were divided into five subgroups, including group 1 (patients 1-10), group 2 (11-20), group 3 (21-30), group 4 (31-40) and group 5 (41-50). The kappa statistics was calculated to assess interobserver agreement between the physicians and the false positive rates of urologists and residents were also compared.. Histologically verified tumors were diagnosed in 103 of 142 lesions identified by PDD. The interobserver agreement between urologists and residents was moderate, moderate, good, excellent, and excellent for group 1, 2, 3, 4, and 5, respectively. Both residents had increased false positive rates compared to urologists in all subgroups of patients but this difference did not reach statistical significance. In addition, false positive rate of residents was declining as the number of procedures was increasing.. Our data suggest that 20 cases of HAL PDD are required to achieve a good interobserver agreement between inexperienced and experienced operator, and excellent agreement is achieved after 30 cases. The false positive rate of inexperienced operators was comparable to the experts and showed a gradual decrease.

Topics: Aged; Aged, 80 and over; Aminolevulinic Acid; Carcinoma; Clinical Competence; Cystoscopy; False Positive Reactions; Female; Fluorescence; Humans; Learning Curve; Light; Male; Middle Aged; Observer Variation; Photosensitizing Agents; Prospective Studies; Urinary Bladder Neoplasms

Nasopharyngeal carcinoma (NPC) is a prevalent cancer in Hong Kong and southern China. To explore a new modality of NPC treatment, 5-aminolevulinic acid (ALA) or its hexyl ester (ALA-H) mediated photodynamic therapy (PDT) was studied in vitro. The results show that NPC cells are sensitive to both ALA and ALA-H mediated PDT. However, ALA-H PDT is much more effective at cell inactivation than ALA-PDT, due to a higher efficiency of ALA-H on producing endogenous protoporphyrin (PpIX) in cells. Both apoptosis and necrosis are involved in cell death, but apoptosis plays a major role under the short time incubation of drugs. ALA and ALA-H mediated PDT not only destroy the cells directly, but also inhibit the expression of matrix metalloproteinase-2 (MMP2) in cells, a maker for tumor metastasis. The ALA-H shows promising PDT results on NPC in vitro; therefore it is worth investigating further in vivo for NPC treatment.

Topics: Aminolevulinic Acid; Apoptosis; Carcinoma; Cell Line, Tumor; Cell Proliferation; Dose-Response Relationship, Drug; Flow Cytometry; Humans; Matrix Metalloproteinase 2; Microscopy, Fluorescence; Nasopharyngeal Neoplasms; Neoplasm Metastasis; Photochemotherapy; Photosensitizing Agents

Photodynamic therapy (PDT) typically involves systemic or topical administration of a tumor-localizing photosensitizer or prodrug and its subsequent activation by visible light. This results primarily in singlet oxygen-induced photodamage to the tumor. 5-Aminolevulinic acid (ALA) and its derivatives have recently been widely used for PDT due to their selective induction in tumor of endogenous protoporphyrin IX (PpIX), a potent photosensitizer. Although ALA-PDT has achieved successful results in the treatment of several clinical oncological and nononcological diseases, the mechanisms of this modality are still not fully elucidated. In the present study, the human colon carcinoma cell line 320DM was treated in vitro with PDT using hexaminolevulinate (HAL), a hexylester of ALA known to be 50 to 100 times more efficient at producing PpIX formation than ALA itself. PpIX production increased with increasing HAL concentrations in the cells and phototoxicity of the cells was enhanced with increasing light (450 nm) doses. HAL-PDT induced apoptotic cell death, as measured by nuclear staining of Hoechst 33342 for fluorescence microscopy, DNA electrophoresis and TdT staining for flow cytometry. PDT with 5 muM of HAL and a light dose of 640 mJ/cm2 produced a 75% apoptotic cell population 40 hr after the treatment. Furthermore, the loss of mitochondrial membrane potential coincident with the release of cytochrome c from the mitochondria into the cytosol led to a rapid activation of caspase-9 and caspase-3 (an executioner), indicating that the selective damage to the mitochondria by HAL-PDT can induce a cytochrome-c-mediated apoptotic response in the 320DM cells.

Topics: Aminolevulinic Acid; Apoptosis; Carcinoma; Caspase 3; Caspase 9; Caspases; Cell Line, Tumor; Cell Survival; Colonic Neoplasms; Cytochromes c; DNA Fragmentation; Humans; Membrane Potentials; Mitochondria; Photochemotherapy; Photosensitizing Agents; Protoporphyrins