No clinical benefit from sequential combination of mitomycin C plus bacillus Calmette-Guérin (BCG) than BCG alone in the adjuvant treatment of high risk non muscle invasive bladder cancer: result of a planned interim analysis of a prospective randomized trial.

BACKGROUND: The aim of this study was to evaluate whether the sequential use of Mitomycin C (MMC) and Bacillus Calmette-Guérin (BCG) is superior to BCG alone in reducing the risk of disease recurrence in patients with non-muscle invasive bladder cancer (NMIBC) with high risk of progression. METHODS: Prospective randomized trial was conducted from March 2021 to March 2023 and included 72 patients with high risk NMIBC. Trial registration number: NCT03790384; EUDRACT Number: 2017-004540-37. Thirty-one patients underwent to BCG alone and forty-one to MMC plus BCG during the induction course. The BCG schedule comprised six weekly instillation of 81 mg Connaught strain BCG as the induction course, followed by a further three-monthly instillation at three, six and twelve months, as the maintenance course. Forty mg of MMC were administered the day prior to each weekly BCG instillation in BCG plus MMC arm. A planned interim analysis was carried out in June 2023, at the end of the 12mo follow-up period. RESULTS: Six out of thirteen 6/31(19.3%) and 10/41 (24.4%) patients experienced recurrence in BCG and BCG plus MMC group (P=0.611), respectively. BCG plus MMC did not improve Disease Free Interval (HR: 1.23 95% CI:0.46-3.50; P=0.640). Patients receiving sequential treatment experienced similar AEs (P>0.05) and more urinary symptoms (P<0.05). CONCLUSIONS: This interim pre-planned analysis suggested absence of clinical advantages in terms of disease recurrence rate when MMC is administered one day prior to BCG during induction course.

[HIPEC morbidity and implications for post-surgical treatment. A medical oncologist advice]. / Effets secondaires des CHIP et implications sur les traitements post-chirurgicaux. L'avis d'une oncologue médicale.

The fear that the medical oncologist may have is that HIPEC integrated into a multidisciplinary care pathway will negatively impact the treatments that will follow. This fear is largely related to the side effects, which are themselves dependent on the medication used. Cisplatin, most frequently used for epithelial ovarian cancers, has essentially renal toxicity, which can be avoided by the use of sodium thiosulfate. Oxaliplatin induces more severe toxicities post surgery than mitomycin C in colorectal cancers. However, the data from randomized trials are reassuring for the medical oncologist concerning the course of postoperative treatment, as long as HIPEC is performed according to a standardized protocol, within trained teams, and after multidisciplinary discussion concerning its modalities.

Comparative study between mitomycin C versus Bacillus Calmette-Guérin (BCG) in high-risk non-muscle-invasive bladder cancer.

OBJECTIVES: We aimed to compare the efficacy and adverse events of Bacillus Calmette-Guérin (BCG) versus Mitomycin C (MMC) in high-risk Non-Muscle-Invasive Bladder Cancer (NMIBC) patients. METHODS: This randomized controlled study was conducted over 24 months in four hospitals in Egypt. A sample of 90 patients was randomly assigned to either treatment group, with procedures including baseline examinations, a single postoperative instillation of chemotherapy, a 6-week induction cycle of the assigned drug, and regular follow-up cystoscopies and upper urinary tract imaging. Treatment results and side effects were monitored, with data analyzed via Statistical Package for Social Sciences (SPSS). RESULTS: No significant differences were observed in mean age or tumor characteristics (p > 0.05). However, adverse reactions were significantly higher in the BCG group, including cystitis (40% vs. 17.78%, p = 0.020), hematuria (24.44% vs. 4.44%, p = 0.007), overall local reactions (75.56% vs. 26.67%, p < 0.001), fever (13.33% vs. 2.22%, p = 0.049), and fatigue (17.78% vs. 2.22%, p = 0.014). The MMC group had a slightly higher recurrence rate (28.89% vs. 17.78%, hazard ratio 1.89, 95% CI: 0.78-4.55, p = 0.15) with a shorter median time to recurrence (six vs. 12 months). Progression rates were similar (8.89% MMC vs. 4.44% BCG, p = 0.398). CONCLUSION: Although BCG and MMC have comparable efficacy in managing high-risk NMIBC, BCG demonstrated a higher rate of adverse reactions. Decision-making should consider this balance, patient preferences, and health status. Further research is needed for the validation and exploration of these findings.

A case of mitomycin C toxicity after XEN gel stent implantation with the XEN air technique in a glaucoma patient.

BACKGROUND: To discuss the first case of mitomycin C (MMC) toxicity after XEN® gel stent implantation in a glaucoma patient, conducted using the XEN "air" technique with an ophthalmic viscosurgical device (OVD). CASE PRESENTATION: A 44-year-old Asian male presented with increased intraocular pressure (IOP; 52 mmHg) accompanied by keratic precipitates and an edematous cornea. He was diagnosed with uveitic glaucoma in the left eye, and the IOP was controlled with a topical anti-glaucoma agent. However, glaucoma progression was revealed by Humphrey visual field (HVF) and optical coherence tomography (OCT) examinations. The patient underwent uneventful XEN gel stent implantation using the XEN air technique and an MMC (0.02%, 0.1 mL) injection, with subconjunctival air and OVD injection provided prior to XEN implantation in the left eye. The patient exhibited a decreased IOP (11 mmHg), elevated bleb, and extensive subconjunctival hemorrhage on postoperative day 1. On postoperative day 18, diffuse conjunctival injection and a large avascular bleb was noticed around the XEN gel stent. The patient complained of severe eye pain and discomfort, suggestive of MMC toxicity, and the IOP was 12 mmHg. The patient was treated with a topical steroid and antibiotics tapered over a 6-month period. Finally, the toxicity was successfully controlled, with the IOP stabilizing at around 15 mmHg. CONCLUSIONS: Although significantly greater lowering of the IOP can be expected with the use of subconjunctival OVD injection and MMC during XEN gel stent implantation, a cautious approach and a longer monitoring period are required.

Panitumumab in combination with chemoradiotherapy for the treatment of locally-advanced anal canal carcinoma: Results of the FFCD 0904 phase II trial.

BACKGROUND AND PURPOSE: Standard treatment of squamous cell carcinoma of the anus (SCCA)is 5-fluorouracil (5FU) and mitomycin C (MMC) based chemoradiotherapy (CRT). This phase II study (EudraCT: 2011-005436-26) assessed the tolerance and complete response (CR) rate at 8 weeks of panitumumab (Pmab) combined with MMC-5FU-based CRT. METHODS: Patients with locally advanced tumors without metastases (T2 > 3 cm, T3-T4, or N + whatever T stage) were treated with IMRT up to 65 Gy and concomitant CT according to the doses defined by a previous phase I study (MMC: 10 mg/m2; 5FU: 400 mg/m2; Pmab: 3 mg/kg). The expected CR rate was 80%. RESULTS: Forty-five patients (male: 9, female: 36; median age: 60.1 [41.5-81]) were enrolled in 15 French centers. The most common related grade 3-4 toxicities observed were digestive (51.1%), hematologic (lymphopenia: 73.4%; neutropenia: 11.1%), radiation dermatitis (13.3%), and asthenia (11.1%) with RT interruption in 14 patients. One patient died because of mesenteric ischemia during the CRT, possibly related to treatment. In ITT analysis, the CR rate at 8 weeks after CRT was 66.7% [90%CI: 53.4-78.2]. Median follow-up was 43.6 months [IC 95%: 38.61-47.01]. Overall survival, recurrence-free and colostomy-free survival at 3 years were 80% [95%CI: 65.1-89], 62.2% [IC95%: 46.5-74.6] and 68.8 % [IC95%: 53.1-80.2] respectively. CONCLUSION: Panitumumab in combination with CRT for locally advanced SCCA failed to meet the expected CR rate and exhibited a poor tolerance. Furthermore, late RFS, CFS, and OS did not suggest any outcome improvement to justify further clinical trials. CLINICALTRIALS: gov identifier: NCT01581840.

Complete Remission of BCG-Refractory High-grade Bladder CIS with Pharmacologic Ascorbate and Mistletoe.

Context: Bladder cancer is the fourth-most-common cancer in males in the U.S., who develop about 90% of the high-grade, carcinoma in situ (CIS) of non-muscle involved disease (NMIBC). Smoking and occupational carcinogens are well-known causes. For females without known risk factors, bladder cancer can be regarded as a sentinel environmental cancer. It's also one of the costliest to treat due to its high rate of recurrence. No treatment innovations have occurred in nearly two decades; intravesical instillation of Bacillus Calmette-Guerin (BCG), an agent in short supply globally, or Mitomycin-C (MIT-C) is effective in about 60% of cases. Cases refractory to BCG and MIT-C often undergo cystectomy, a procedure with numerous impacts on life styles and potential complications. The recent completion of a small Phase I trial of mistletoe in cancer patients that have exhausted known treatments at Johns Hopkins provides corroboration of its safety, with 25 % showing no disease progression. Objective: The study examined the benefits of pharmacologic ascorbate (PA) and mistletoe for a nonsmoking female patient with an environmental history of NMIBC refractory to BCG, in a non-smoking female with exposures in childhood and early adult life to several known carcinogens, including ultrafine particulate air pollution, benzene, toluene, and other organic solvents, aromatic amines and engine exhausts, and possibly arsenic in water. Design: The research team performed an integrative oncology case study on pharmacologic ascorbate (PA) and mistletoe, both agents shown to activate NK cells, enhance growth and maturation of T-cells, and induce dose-dependent pro-apoptotic cell death, suggesting shared and potentially synergistic mechanisms. Setting: The study began at the University of Ottawa Medical Center in Canada with treatment continuing over six years at St. Johns Hospital Center in Jackson, Wyoming, and George Washington University Medical Center for Integrative Medicine, with surgical, cytological, and pathological evaluations at University of California San Francisco Medical Center. Participant: The patient in the case study was a 76-year-old, well-nourished, athletic, nonsmoking female with high-grade CIS of the bladder. Her cancer was considered to be a sentinel environmental cancer. Intervention: Intravenous pharmacologic ascorbate (PA) and subcutaneous mistletoe (three times weekly) and intravenous and intravesical mistletoe (once weekly) were employed for an 8-week induction treatment, using a dose-escalation protocol as detailed below. Maintenance therapy was carried out with the same protocol for three weeks every three months for two years. Results: The patient has experienced a cancer-free outcome following 78 months of treatments that incorporated intravesical, intravenous, and subcutaneous mistletoe; intravenous PA; a program of selected nutraceuticals; exercise; and other supplementary treatments. Conclusions: This study is the first reported instance of combined treatments to achieve complete remission for high-grade NMIBC refractory to BCG and MIT-C, using intravesical, subcutaneous, and intravenous mistletoe and intravenous PA. It includes pharmacological information on possible mechanisms. In light of the global shortage of BCG, the high proportion of cases refractory to BCG and MIT-C, the unproven use of costly off-label pharmaceuticals, such as gemcitabine, and the relative cost-effectiveness of mistletoe and PA, clinicians should give serious consideration to employing these combined functional medicine treatments for BCG- and MIT-C-refractory NMIBC. Further research is needed with additional patients that can advance our understanding, including standardization of methods for systematically evaluating combined therapies-blinded and non-blinded, nomenclature regarding mistletoe preparation, doses, concentrations, regimes of administration, lengths of treatment, targeted cancer types, and other aspects.

Pegylated Liposomal Mitomycin C Lipidic Prodrug in Combination With External Beam Radiation Therapy in Patients With Advanced Cancer: A Phase 1B Study.

PURPOSE: The aim of this study was to evaluate a formulation of pegylated liposomal mitomycin C lipidic prodrug (PL-MLP) in patients concomitantly undergoing external beam radiation therapy (RT). METHODS AND MATERIALS: Patients with metastatic disease or inoperable primary solid tumors requiring RT for disease control or symptom relief were treated with 2 courses of PL-MLP (1.25, 1.5, or 1.8 mg/kg) at 21-day intervals, along with 10 fractions of conventional RT or 5 stereotactic body RT fractions initiated 1 to 3 days after the first PL-MLP dose and completed within 2 weeks. Treatment safety was monitored for 6 weeks, and disease status was re-evaluated at 6-week intervals thereafter. MLP levels were analyzed 1 hour and 24 hours after each PL-MLP infusion. RESULTS: Overall, 19 patients with metastatic (18) or inoperable (1) disease received combination treatment, with 18 completing the full protocol. Most patients (16) had diagnoses of advanced gastrointestinal tract cancer. One grade 4 neutropenia event possibly related to study treatment was reported; other adverse events were mild or moderate. Of the 18 evaluable patients, 16 were free of RT target lesion progression at first re-evaluation. Median survival of the entire patient population was 63.3 weeks. Serum MLP level correlated with dose increases and similar long circulating profiles were observed before and after RT. CONCLUSIONS: PL-MLP up to 1.8 mg/kg in combination with RT treatment is safe, with a high rate of tumor control. Drug clearance is not affected by radiation. PL-MLP is potentially an attractive option for chemoradiation therapy that warrants further evaluation in randomized studies in the palliative and curative settings.

Adjuvant intravesical treatment in patients with intermediate and high-risk non-muscle-invasive bladder cancer with BCG versus MMC applied with COMBAT or EMDA. Results of a prospective study.

BACKGROUND: Bacillus Calmette-Guerin (BCG) maintenance therapy is the standard adjuvant treatment of high- and intermediate-risk non-muscle-invasive bladder cancer (NMIBC). However, the problems of shortages and the adverse effects, both local and systemic, that it causes lead to the search for alternatives with devices that improve the penetration of intravesical chemotherapeutics. MATERIALS AND METHODS: Prospective observational study was conducted from August 2018 to August 2022. Patients diagnosed with intermediate and high-risk NMIBC without CIS who received one of the following three treatments were included: BCG in induction protocol with six weekly instillations and maintenance with three weekly instillations at months 3, 6, and 12. MMC was applied by Physionizer® 30 device with a current of 20 mA for 30 min was used in an induction protocol of 6 weekly instillations followed by 6 monthly instillations as maintenance (EMDA group). MMC was applied by COMBAT BRS System V2.0 device at 43 ± 0.5 â„ƒ for 60 min was used in an induction protocol of 6 weekly instillations followed by 6 monthly instillations as maintenance (HIVEC group). The primary objective was to compare the 24-month recurrence-free rate between the three groups. The secondary objectives were to evaluate the rate free of progression at 24 months and the degree of toxicity of the treatments. RESULTS: One hundred and eighty-three patients divided into a HIVEC group with sixty-one patients, EMDA group with fifty-nine patients, and BCG group with sixty-three patients. After a mean follow-up of 25 months (IQR 13-36), the 24-month recurrence-free rate was 82.1% for HIVEC, 80% for EMDA, and 84.6% for BCG (p > 0.05), and a progression-free rate at 24 months of 95.6% for HIVEC, 98.3% for EMDA, and 92.9% for BCG (p > 0.05). No statistically significant differences were found between the three groups with respect to the degree of reported adverse events. CONCLUSION: Adjuvant treatment with BCG or MMC applied with COMBAT or EMDA does not present differences in the recurrence-free rate and progression at 24 months in our population of patients with intermediate- and high-risk NMBC without CIS.

Inadvertent filtering bleb due to extracapsular cataract extraction wound reopening after mitomycin C use: a case report.

BACKGROUND:  Mitomycin C has been used adjunctively in various procedures, including pterygium excision. Delayed wound healing, the long-term complication of mitomycin C, can occur several years later and may rarely cause a subsequent inadvertent filtering bleb. However, conjunctival bleb formation from the reopening of an adjacent surgical wound after mitomycin C use has not been reported. CASE PRESENTATION: A 91-year-old Thai woman had undergone pterygium excision 26 years ago, with adjunctive mitomycin C, as well as an uneventful extracapsular cataract extraction in the same year. The patient developed a filtering bleb without glaucoma surgery or trauma approximately 25 years later. Anterior segment ocular coherence tomography illustrated a fistula connected between the bleb and anterior chamber at the scleral spur. The bleb was observed without further management, as no hypotony or bleb-related complications occurred. The symptoms/signs of bleb-related infection were advised. CONCLUSIONS:  This is a case report of a rare novel complication of mitomycin C application. Conjunctival bleb formation from the reopening of surgical wound, which was related to the previous mitomycin C use, could occur after a few decades.

Evaluation of dosimetric predictors of toxicity after IMRT with concurrent chemotherapy for anal cancer.

BACKGROUND: This study investigates the impact of dosimetric parameters on acute and late toxicity for patients with anal squamous cell carcinoma (SCC) treated with image-guided intensity modulated radiation therapy (IG-IMRT) and concurrent chemotherapy. MATERIALS AND METHODS: Patients were enrolled in an observational cohort study between 2008 and 2013 (median follow-up 3.4 years). They were treated with standardized target and organ-at-risk (OAR) contouring, planning, and IG-IMRT. Radiotherapy dose, based on clinicopathologic features, ranged from 45 Gy to 63 Gy to gross targets and 27 Gy to 36 Gy to elective targets. Chemotherapy was concurrent 5-fluorouracil and mitomycin C (weeks 1&5). Toxicity was prospectively graded using NCI CTCAE v.3 and RTOG scales. Logistic regression was used to assess the association between dose/volume parameters (e.g small bowel V5) and corresponding grade 2 + and 3+ (G2+/3 + ) toxicities (e.g. diarrhea). RESULTS: In total, 87 and 79 patients were included in the acute and late toxicity analyses, respectively. The most common acute G2 + toxicities were skin (dermatitis in 87 % [inguino-genital skin], 91 % [perianal skin]) and hematologic in 58 %. G2 + late anal toxicity (sphincter dysfunction), gastrointestinal toxicity, and skin toxicity were respectively experienced by 49 %, 38 %, and 44 % of patients. Statistically significant associations were observed between: G2 + acute diarrhea and small bowel V35; G2 + acute genitourinary toxicity and bladder D0.5cc; G2 + inguino-genital skin toxicity and anterior skin V35; G2 + perianal skin toxicity and posterior skin V15; G2 + anemia and lower pelvis bone V45. D0.5 cc was significantly predictive of late toxicity (G2 + anal dysfunction, intestinal toxicity, and inguino-genital/perianal dermatitis). Maximum skin toxicity grade was significantly correlated with the requirement for a treatment break. CONCLUSION: Statistically significant dose-volume parameters were identified and may be used to offer individualized risk prediction and to inform treatment planning. Additional validation of the results is required.

Comparison of cisplatin and mitomycin C/5-FU as radiosensitisers in the treatment of locally advanced vulvar cancer: results of a retrospective, observational, single-institutional cohort study.

PURPOSE: We retrospectively investigated the widely used radiosensitisers cisplatin and mitomycin C/5-fluorouracil (5-FU) in patients with locally advanced vulvar cancer for outcome and toxicity. METHODS: We screened the archive for patients treated with chemoradiation for vulvar cancer diagnosed between 01/2010 and 08/2021 at our institution. The impact of both radiosensitisers on prognosis was compared using Kaplan-Meier method and Cox-regression analysis. RESULTS: One hundred and forty-three patients with vulvar cancer were screened. Twenty-nine patients received chemoradiation (mitomycin C/5-FU n = 14; cisplatin n = 12; others n = 3) as a primary, neoadjuvant or adjuvant treatment. Median follow-up was 15.5 months. Patients in the cisplatin group were older (mean age 54.4 vs. 70.7; p = 0.004). However, the mitomycin C/5-FU group had more advanced tumour stages. The 2-year recurrence-free survival (RFS) was comparable (44.5% vs. 33.3%; p = 0.932). The 2-year overall survival (OS) showed a numerical but not statistically significant difference in favour of the mitomycin C/5-FU group (59.7% vs. 31.7%; p = 0.37). 64.3% (9 out of 14) patients, who received mitomycin C/5-FU achieved clinical complete response (cCR) compared to 41.7% (5 out of 12) who received cisplatin (p = 0.505). Radiodermatitis was the most common adverse event in both groups (81%) and more severe in the mitomycin C/5-FU cohort. Myelotoxicity was frequently observed in both groups. Eighteen patients received an additional radiation boost with 10.0 (9-16) Gy and showed a significantly prolonged RFS (p = 0.027) and OS (p = 0.003). CONCLUSION: Mitomycin C/5-FU may be considered in the treatment of young and healthy patients with locally advanced vulvar cancer.

DaBlaCa-13 Study: Oncological Outcome of Short-Term, Intensive Chemoresection With Mitomycin in Nonmuscle Invasive Bladder Cancer: Primary Outcome of a Randomized Controlled Trial.

PURPOSE: This study aimed to assess long-term follow-up after chemoresection with mitomycin (MMC), a nonsurgical treatment modality for recurrent nonmuscle invasive bladder cancer (NMIBC). At the time of recurrence, chemoresection has previously been shown to reduce the number of patients requiring a procedure (transurethral resection of bladder tumors [TURBT] or office biopsy) by more than 50%. This study investigated the number of patients requiring a procedure during initial treatment and 2-year follow-up in patients treated with short-term, intensive chemoresection with MMC compared with patients undergoing standard surgical treatment of recurrent NMIBC. METHODS: A randomized, controlled trial was conducted in two urological departments in Denmark from January 2018 to August 2021. In total, 120 patients with a history of Ta low- or high-grade NMIBC were included upon recurrence. The intervention group received intravesical MMC (40 mg/40 mL) three times a week for 2 weeks and TURBT or office biopsy only if the response was incomplete. The control group received TURBT or office biopsy and 6 weekly adjuvant instillations. The primary outcome was the number of patients undergoing a procedure within 2 years from inclusion, which was compared between groups using the chi-squared test. Recurrence-free survival was analyzed using the Kaplan-Meier method. RESULTS: Significantly fewer patients were in need of a procedure in the intervention group than in the control group: 71% (95% CI, 57 to 81) and 100% (95% CI, 94 to 100), P < .001. The 12-month recurrence-free survival was 36% (95% CI, 24 to 50) and 43% (95% CI, 30 to 56) in the intervention and control groups, respectively (P = .5). CONCLUSION: Short-term intensive chemoresection is an effective treatment strategy for recurrent NMIBC that leads to a reduced number of required procedures without compromising long-term oncological safety.

A comparative analysis of surgical outcome in uveitic and non-uveitic steroid-induced glaucoma in children.

Purpose: To compare outcomes of surgical management of uveitic glaucoma (UG) and steroid-induced glaucoma (SIG) in children in terms of intraocular pressure (IOP) control, visual acuity, and associations for failure. Methods: This was a retrospective case-control study of consecutive UG (cases) and non-uveitic SIG (controls) in children <18 years of age who underwent surgery between January 2005 and December 2017. Results: Primary trabeculectomy with mitomycin C (MMC) was performed in 12 cases (mean age: 9.2 ± 4.3 years) and 40 controls (mean age: 10.4 ± 3.7 years) (P = 0.33). Primary phaco-trabeculectomy with MMC was performed in 11 cases (mean age: 11.4 ± 4.7 years) and 16 controls (mean age: 10.4 ± 3.4 years) (P = 0.57). IOP control (P = 0.26), visual acuity (P = 0.97), number of glaucoma medications (P = 0.06), and survival rates (49% cases vs. 68% controls at 5 years; P = 0.22) were similar between the two groups following trabeculectomy. Survival rates in the phaco-trabeculectomy group at 5 years were 68% cases vs. 69% controls (P = 0.71). IOP was higher (P = 0.008) and visual acuity was worse (P = 0.02) in cases at the last visit. Associations for failure (univariate analysis) were younger age (OR: 6.29, 95% CL: 1.43, 27.67; P = 0.03) and male gender (OR: 4.79, 95% CL: 1.09, 20.97; P = 0.04). On multivariate analysis, younger age (OR: 11.985, 95% CL: 1.071, 134.153; P = 0.04) remained significant. Preoperative number of uveitic attacks was protective on univariate (OR: 0.75, 95% CL: 0.48, 1.15; P = 0.1) and multivariate analyses (OR: 0.49, 95% CL: 0.24, 0.09; P = 0.04). Conclusion: Outcomes of trabeculectomy between cases and controls were similar in our series. However, phaco-trabeculectomy in pediatric uveitic eye group fared worse than eyes with SIG.

Minimal Patient-Reported Side Effects for a Chemoablative Gel (UGN-102) Used as Frontline Treatment in Adults with Nonmuscle-Invasive Bladder Cancer.

PURPOSE: Optima II ("OPTimized Instillation of Mitomycin for Bladder Cancer Treatment," clinicaltrials.gov: NCT03558503) was a phase 2b trial evaluating a nonsurgical alternative as a primary treatment for nonmuscle-invasive bladder cancer (NMIBC). Patients received 6 weekly instillations of UGN-102, a mitomycin-containing reverse thermal gel. This is the first study to report on patient-reported side effects of UGN-102. MATERIALS AND METHODS: Sixty-three patients enrolled in Optima II from 20 sites. Of these 63 patients, 44 were in the cohort completing a quarterly patient-reported outcome measure assessing side effects. Changes in side effects were evaluated using the Wilcoxon signed-rank test. Associations of 3-month outcomes with demographic and clinical characteristics were examined with regression, controlling for baseline values. Ten of 44 patients (23%) were interviewed after the trial to understand tolerability for future patients making treatment decisions. Transcripts were double-coded using standard methods. RESULTS: In the patient-reported outcome measure cohort (44), 61% were men, 57% aged 65+ years and 89% were non-Hispanic White. UGN-102 did not cause decrements in patient-reported urinary symptoms, bloating/flatulence or malaise at the primary endpoint of 3 months. Sexual function mildly worsened. Future health worries improved. Demographics were not correlated with changes. Clinically, sexual function was correlated with new NMIBC and bloating/flatulence was associated with transurethral resection of bladder tumor within 12 months. In interviews, patients appreciated a nonsurgical alternative, would recommend the gel to other patients and would choose the gel over surgery. CONCLUSIONS: A nonsurgical, chemoablative gel (UGN-102) used as a primary treatment for NMIBC offers a more patient-centered therapeutic approach than standard treatments.

[Transcription of DNA-Methyltransferases in Endothelial Cells Exposed to Mitomycin C].

DNA-methyltransferases catalyze DNA methylation in the CpG sites, which play an important role in the maintenance of genome stability. The association between DNA methylation and genotoxic stress resulting in the action of various clastogens has been shown. Genotoxic stress is one of the triggers of endothelial dysfunction. In this study, the transcription of DNMT1, DNMT3A and DNMT3B genes in coronary (HCAEC) and internal thoracic (HITAEC) artery endothelial cells exposed to alkylating mutagen mitomycin C was studied using quantitative polymerase chain reaction. In HCAEC exposed to mitomycin C, DNMT1 transcription is 1.7-fold higher compared to the unexposed control. After elimination of the mutagen from the cultures followed by 24-hours of cultivation, a 2-fold increase of transcription of DNMT3B in HCAEC exposed to mitomycin C compared to the control was observed. At the same time, no changes in transcription of the studied DNA-methyltransferases were found in HITAEC exposed to the mutagen. Thus, increased transcription of DNA-methyltransferase may be a possible molecular mechanism underlying endothelial dysfunction in response to mutagenic load in an in vitro experiment.

Definitive Intensity-Modulated Chemoradiation for Anal Squamous Cell Carcinoma: Outcomes and Toxicity of 428 Patients Treated at a Single Institution.

BACKGROUND: Although intensity-modulated radiation therapy (IMRT) is considered the standard of care for the treatment of squamous cell carcinoma of the anus (SCCA), few large series have reported oncologic outcomes and toxicities. In this retrospective report, we aim to describe outcomes and toxicities after IMRT-based chemoradiation (CRT) for the treatment of SCCA, evaluate the impact of dose escalation (>54 Gy), and compare concurrent fluoropyrimidine in combination with either mitomycin or with cisplatin as chemosensitizers. METHODS: Patients treated at The University of Texas MD Anderson Cancer Center between January 1, 2003 and December 31, 2018 with IMRT-based CRT were included. Median time to locoregional recurrence, time to colostomy, and overall survival were estimated using the Kaplan-Meier method. RESULTS: A total of 428 patients were included; median follow-up was 4.4 years. Three hundred and thirty-four patients (78.0%) were treated with concurrent cisplatin and fluoropyrimidine, and 160 (37.4%) with >54 Gy. Two- and 5-year freedom from locoregional failure, freedom from colostomy failure, and overall survival were 86.5% and 81.2%, respectively, 90.0% and 88.3%, respectively, and 93.6% and 85.8%, respectively. Neither dose escalation nor mitomycin-based concurrent chemotherapy resulted in improved outcomes. Mitomycin-based concurrent chemotherapy was associated with in approximately 2.5 times increased grade 3 or greater acute toxicity. Radiation dose >54 Gy was associated with approximately 2.6 times increased Grade 3 or greater chronic toxicity. CONCLUSIONS: Our results suggest IMRT-based CRT with concurrent fluoropyrimidine and cisplatin is a safe and feasible option for patient with SCCA and may cause less acute toxicity. The role for radiation dose escalation is unclear and requires further study.

Antegrade Instillation of UGN-101 (Mitomycin for Pyelocalyceal Solution) for Low-Grade Upper Tract Urothelial Carcinoma: Initial Clinical Experience.

PURPOSE: UGN-101 (mitomycin for pyelocalyceal solution) is a recently approved chemoablative treatment for low-grade (LG) upper tract urothelial carcinoma (UTUC). While approved for retrograde or antegrade administration, previous reports discuss only patients treated by retrograde approach. We report our techniques for antegrade administration along with early outcomes from our cohort of patients who have undergone UGN-101 administration via nephrostomy. MATERIALS AND METHODS: UGN-101 is administered as 6 weekly instillations in patients who have undergone endoscopic ablation of LG UTUC. We outline our approach in patients thought to have LG UTUC from initial ureteroscopy to nephrostomy placement, UGN-101 administration and eventual nephrostomy removal. We discuss early durability of response along with adverse events with special attention to ureteral strictures. RESULTS: Eight patients underwent antegrade UGN-101 administration during the study period, all of whom underwent followup ureteroscopy with complete response in 4 patients. Three patients reported 5 adverse events-3 grade 1, 1 grade 2 requiring 1 week delay of treatment and 1 asymptomatic ureteral stricture. Median followup was 7 months. CONCLUSIONS: We outline our approach for antegrade administration of UGN-101 and discuss early results along with adverse events. Future studies should evaluate our method's potential to increase patient comfort, improve logistics and decrease risk of adverse events.

[Guidelines from the cancer committee of the French Association of Urology (CC-AFU) for adequate intravesical instillations of Mitomycin C, Epirubicin, and BCG for non-muscle invasive bladder cancer]. / Recommandations du Comité de cancérologie de l'Association Française d'Urologie (CC-AFU) pour la bonne pratique des instillations intravésicales de mitomycine C, d'épirubicine et de BCG pour le traitement des tumeurs de la vessie n'infiltrant pas le muscle (TVNIM).

INTRODUCTION: Intravesical instillations of mitomycin C, epirubicin and BCG are considered as the standard treatment for most patients diagnosed with non-muscle invasive bladder cancer. These guidelines aim to optimize the adjuvant intravesical treatment in order to increase the efficacy and lower the morbidity associated with its administration. METHODS: We conducted a daily practice survey, an online search of available national regulation recommendations and of published guidelines. A bibliography search in French and English using Medline® and Embase® with the keywords "BCG"; "mitomycin C"; "epirubicin"; "bladder"; "complication"; "toxicity"; "adverse reaction"; "prevention" and "treatment" was performed November 2021. RESULTS: Patient information should be given by the attending physician before the first intravesical instillation. A medical exam to look for specific contraindications is also mandatory to select adequate candidates. Intravesical instillations should be delivered in health-care centers where urologic endoscopic procedures are routinely performed. Attending urologist or specialized nurse should check for negative pretreatment urine test. Intravesical instillation can only be delivered after bladder catheter has been inserted in the bladder without any injury of the lower urinary tract. The pharmaceutical agent should be kept in the bladder for two hours. Finally, voiding within the 6hours following intravesical instillations should be done in the sitting position and the patient should drink at least 2 liters of water per day for 2 days. CONCLUSION: The delivery of intravesical instillations of mitomycin C, epirubicin and BCG should follow a standardized procedure for better efficacy and lower morbidity.