Injection Of 5-fluorouracil Research Articles

Treatment of keloid scars with intralesional triamcinolone and 5-fluorouracil injections – a randomized controlled trial

Keloids have high recurrence rates. Current first-line therapy is triamcinolone (TAC) injection, but it has been suggested that approximately 50% of keloids are steroid resistant. We compared the efficacy of intralesional 5-fluorouracil (5-FU) and triamcinalone injections in a double-blind randomized controlled trial. Forty-three patients with 50 keloid scars were treated with either intralesional TAC or 5-FU-injections over 6 months. There was no statistically significant difference in the remission rate at 6 months between the 5-FU and TAC groups (46% vs 60%, respectively). Local adverse effects were higher in the TAC group compared to the 5-FU group. Occurrence of skin atrophy in TAC group was 44% and in the 5-FU group 8% (p < 0.05). Also the occurrence of telangiectasia in the TAC group was 50% and in the 5-FU 21% (p < 0.05). Vascularity of the keloids, assessed by spectral imaging and immunohistochemical staining for blood vessels, after treatment decreased in the TAC group, but not in the 5-FU group (p < 0.05). Fibroblast proliferation evaluated by Ki-67 staining significantly decreased in the TAC group (p < 0.05) but increased in the 5-FU group (p < 0.05). TAC and 5-FU injections did not differ in their clinical effectivity in this randomized study, but 5-FU injections lead to increased proliferation rate and did not affect vascular density in histological assessment. Due to the greater number of adverse effects observed after TAC treatment, 5-FU injections may be preferable for cosmetically sensitive skin areas.

Effects of Matricaria Recutita (L.) in the Treatment of Oral Mucositis.

Objective The objective of this study was to review the effects of the Matricaria recutita (L.) in the treatment of oral mucositis. Methodology The online search was performed in the period from June 2016 to April 2018 by means of databases LILACS (Latin American and Caribbean Center on Health Sciences Information), SciELO (Scientific Electronic Library Online), and MEDLINE (Medical Literature Analysis and Retrieval System Online). The consultation was restricted to the years 1991 to 2018 with the aim of elucidating the effects of Matricaria recutita in the treatment of oral mucositis. Results The final sample consisted of 21 studies, of which 10 were developed in animals and 11 in humans, published from 1991 to 2017, with a total sample of 644 patients. The total number of patients treated with Matricaria included in 11 studies was 364, while in the control groups the total number was 280. In experimental studies, animal models used were rats and the sample size ranged between 36 and 105 animals submitted to the induction of oral mucositis, where 4 studies used an intraperitoneal injection of 5-fluorouracil, while 7 induced lesion in the mucosa. From the data collected, it should be noted that both studies with humans and with animals showed significant effects. In this way, there is strong evidence for the discussion on the therapy; however, it should be noted that more studies are developed in order to clarify the most appropriate protocol for the prevention and treatment of injuries. Conclusion According to the results found in this study, Matricaria recutita appeared to be a promising alternative for the treatment of oral mucositis. However, due to the great variability in the various types of intervention, more controlled double-blind randomized clinical studies are necessary to ensure the best protocol for treating oral mucositis.

Novel Stereoscopic Optical System for Objectively Measuring Above-Surface Scar Volume-First-Time Quantification of Responses to Various Treatment Modalities.

Current approaches use subjective semiquantitative or cumbersome objective methodologies to assess physical characteristics of hypertrophic and keloid scars. This pilot study aimed to evaluate the accuracy and feasibility of a new stereoscopic optical and high-resolution 3-dimensional imaging system, for objectively measuring changes in above-surface scar volume after various interventions. Feasibility and accuracy were assessed by monitoring the above-surface scar volume of 5 scars in 2 patients for 5 successive months. Above-surface scar volume and Vancouver Scar Scale scores and the investigator and patient volume improvement assessment scores were assessed before and 12 weeks after last intervention. Scar volume measured by the imaging system correlated significantly with the gold standard (actual weight). The greatest volume reduction followed a combination of cryotherapy and intralesional triamcinolone acetonide and 5-fluorouracil injections in Patient 1 and a combination of pulse dye laser and intralesional triamcinolone acetonide injections in Patient 2. The new stereoscopic optical system is a valid, accurate, and practical objective method for assessing scar volume and for monitoring treatment response. It is more sensitive and accurate than semiquantitative objective scales. Further studies with a higher number of patients and scars are required to increase the measurement validity of the system.

Fecal microbiota transplantation reverses antibiotic and chemotherapy-induced gut dysbiosis in mice.

Fecal microbiota transplantation (FMT) is now widely used to treat recurrent Clostridium difficile infection, but has been less studied as a means to restore microbiome diversity and composition following antibiotic or chemotherapy treatments. The purpose of our study was to assess the efficacy of FMT to reverse antibiotic- and chemotherapy-induced gut dysbiosis in a mouse model. C57BL/6J mice were treated with ampicillin for 1 week and/or received a single intraperitoneal injection of 5-Fluorouracil. Fresh stool was collected and analyzed using shotgun metagenomics and the Illumina sequencing platform. Ampicillin caused a significant and immediate decrease in bacterial species richness and diversity that persisted for one week. In mice that received FMT, disruption of the intestinal microbiota was reversed immediately. Antibiotic and chemotherapy administration caused significant alteration in species distribution, including a decrease in the relative proportions of Clostridium scindens and Faecalibacterium prausnitzii, and an increase in known pathogenic species. In mice receiving FMT, we observed a significant increase in species known to exhibit anti-inflammatory properties. Moreover, chemotherapy led to a critical decrease in key ‘health-promoting’ species and to an altered functional profile, especially when chemotherapy was administered in tandem with antibiotics, and that FMT can ameliorate these effects.

Ocular surface changes in recurrent pterygium cases post-operatively treated with 5-fluorouracil subconjunctival injections.

To investigate the ocular surface changes occurring in eyes with recurrent pterygium post-operatively treated with 5-fluorouracil intralesional injections. Retrospective observational study of recurrent pterygium cases treated with weekly intralesional injections of 0.1 mL (5 mg) of 5-fluorouracil (10 injections). Impression cytology samples taken from the lesion, the healthy conjunctivae (inferior, superior, and contralateral to injury), and the cornea before and after treatment were analyzed. Clinical ocular characteristics (including Schirmer's test and break-up time) were evaluated during treatment. A total of 15 eyes were treated, with the mean follow-up of 27 ± 8.7 months (mean ± standard deviation). Prior to treatment initiation, the ocular surface citology over the pterygium was found to be abnormal. No epithelial cells (27%) and a lower goblet cell density (73%) compared to the healthy conjunctivae (p < 0.01) were found. Squamous metaplasia was observed to some degree in the cornea (100%), pterygium (81%) and healthy conjunctivae (73%). Following treatment, pterygium composition had changed: epithelial cell number (100%) and goblet cell density (47%) had increased (p < 0.05). Goblet cell density was also increased in healthy conjunctivae (67%; p < 0.05). The degree of squamous metaplasia decreased in the cornea (67%), pterygium (45%), and healthy conjunctivae (60%; p < 0.05). No adverse effects were reported, recurrence progression was arrested, and conjunctival redness and dry-eye severity level were decreased in all cases (p < 0.01). The cytology of ocular surface in recurrent pterygium is abnormal. After weekly intralesional 5-fluorouracil injections, it tends to normalize. The 5-fluorouracil compound is a safe and effective treatment to prevent pterygium recurrence.

Use of 5-Fluorouracil for Management of the Thick-Skinned Nose.

Patients with a thick nasal skin and soft tissue envelope can have unpredictable results and irregular scarring after rhinoplasty surgery. These patients typically have sebaceous tissue over the nasal tip and are particularly susceptible to soft tissue polly beak formation and excess scar tissue in the radix, tip, and septum. Targeted injections of 5-fluorouracil alone or mixed with low concentrations of steroid can be useful to prevent and treat excess postoperative scar tissue deposition. Ideally, four to six injections are performed every 1 to 4 weeks beginning 1 week postoperatively. The injections are most beneficial when performed within the first 3 months after surgery. Even a single injection may improve outcomes with minimal side effects.

PAN-811 prevents chemotherapy-induced cognitive impairment and preserves neurogenesis in the hippocampus of adult rats.

Chemotherapy-induced cognitive impairment (CICI) occurs in a substantial proportion of treated cancer patients, with no drug currently available for its therapy. This study investigated whether PAN-811, a ribonucleotide reductase inhibitor, can reduce cognitive impairment and related suppression of neurogenesis following chemotherapy in an animal model. Young adult rats in Chemo and Chemo+PAN-811 groups received 3 intraperitoneal (i.p.) injections of methotrexate (MTX) and 5-fluorouracil (5-FU), and those in Saline and Saline+PAN-811 groups received equal volumes of physiological saline at 10-day intervals. PAN-811 in saline was delivered through i.p. injection, 10 min following each saline (Saline+PAN-811 group) or MTX/5-FU (Chemo+PAN-811 group) treatment, while equal volumes of saline were delivered to Saline and Chemo groups. Over Days 31–66, rats were administered tests of spatial memory, nonmatching-to-sample rule learning, and discrimination learning, which are sensitive to dysfunction in hippocampus, frontal lobe and striatum, respectively. On Day 97, neurogenesis was immnunohistochemically evaluated by counting doublecortin-positive (DCX+) cells in the dentate gyrus (DG). The results demonstrated that the Chemo group was impaired on the three cognitive tasks, but co-administration of PAN-811 significantly reduced all MTX/5-FU-induced cognitive impairments. In addition, MTX/5-FU reduced DCX+ cells to 67% of that in Saline control rats, an effect that was completely blocked by PAN-811 co-administration. Overall, we present the first evidence that PAN-811 protects cognitive functions and preserves neurogenesis from deleterious effects of MTX/5-FU. The current findings provide a basis for rapid clinical translation to determine the effect of PAN-811 on CICI in human.

Canaloplasty versus Nonpenetrating Deep Sclerectomy: 2-Year Results and Quality of Life Assessment.

Purpose To compare phacocanaloplasty (PC) and phaco-non-penetrating deep sclerectomy (PDS). Methods 75 patients with uncontrolled glaucoma and cataract were randomized for PC (37 eyes) or PDS (38 eyes). Intraocular pressure (IOP) and number of medications (meds) were prospectively evaluated. Follow-up examinations were performed on days 1 and 7 and after 1, 3, 6, 12, 18, and 24 months. Surgical success was calculated. Complications and postoperative interventions were noted. Quality of life (QoL) was analyzed. Results Preoperatively, mean IOP and meds were comparable (P > 0.05). After 24 months, IOP significantly decreased in PC from 19.4 ± 5.9 mmHg (2.6 ± 0.9 meds) to 13.8 ± 3.3 mmHg (0.5 ± 0.9 meds) and in PDS from 19.7 ± 5.4 mmHg (2.9 ± 0.9 meds) to 15.1 ± 2.9 mmHg (1.1 ± 1.2 meds). Statistically lower IOP was observed in PC in the 6th month and persisted until 24 months (P < 0.05). No difference was found in meds (except for month 18, in which less drugs were used in PC (P = 0.001)) or success rates (P > 0.05). The most frequent complication in PC was transient hyphema (46%), in PDS bleb fibrosis (24%). PC patients during postoperative period required only goniopuncture (22% of subjects), whereas PDS patients required, in order to maintain subconjuctival outflow, subconjunctival 5-fluorouracil injections in 95% of cases (median = 3), suture lysis (34%), needling (24%), and goniopuncture (37%). NEI VFQ-25 mean composite score for PC was 78.04 ± 24.36 points and for PDS 74.29 ± 24.45 (P = 0.136). α Cronbach's correlation coefficient was 0.913. Conclusions PC leads to a more effective decrease in IOP than PDS in midterm observation with similar safety profiles. PDS patients required a vast number of additional procedures in contrast to PC patients, but this fact did not influence QoL.

Metaplastic Cells in the Stomach Arise, Independently of Stem Cells, via Dedifferentiation or Transdifferentiation of Chief Cells

Spasmolytic polypeptide-expressing metaplasia (SPEM) develops in patients with chronic atrophic gastritis due to infection with Helicobacter pylori; it might be a precursor to intestinal metaplasia and gastric adenocarcinoma. Lineage tracing experiments of the gastric corpus in mice have not established whether SPEM derives from proliferating stem cells or differentiated, post-mitotic zymogenic chief cells in the gland base. We investigated whether differentiated cells can give rise to SPEM using a nongenetic approach in mice. Mice were given intraperitoneal injections of 5-fluorouracil, which blocked gastric cell proliferation, plus tamoxifen to induce SPEM. Based on analyses of molecular and histologic markers, we found SPEM developed even in the absence of cell proliferation. SPEM therefore did not arise from stem cells. In histologic analyses of gastric resection specimens from 10 patients with adenocarcinoma, we found normal zymogenic chief cells that were transitioning into SPEM cells only in gland bases, rather than the proliferative stem cell zone. Our findings indicate that SPEM can arise by direct reprogramming of existing cells-mainly of chief cells.

Noninvasive assessment of hepatic sinusoidal obstructive syndrome using acoustic radiation force impulse elastography imaging: A proof-of-concept study in rat models.

To determine the feasibility of acoustic radiation force impulse (ARFI) elastography in the evaluation of hepatic sinusoidal obstruction syndrome (SOS) in rat models. Rat SOS models of various severities were created by monocrotaline gavage (n = 40) or by intraperitoneal injection of 5-fluorouracil, leucovorin and oxaliplatin (FOLFOX) (n = 16). Liver shear-wave velocity (SWV) was measured using ARFI elastography. Liver samples were analysed for the SOS score, steatosis, lobular inflammation and fibrosis. The liver SWV was significantly elevated in the SOS models (1.29-2.24 m/s) compared with that of the matched control rats (1.01-1.09; p≤.09; veFor seven FOLFOX-treated rats which were longitudinally followed-up, the liver SWV significantly increased at 7 weeks (1.32±0.13 m/s) compared with the baseline (1.08±0.1 m/s, p=.015) and then significantly declined after a 2-week, treatment-free period (1.15±0.13 m/s; p=.048). Multivariate analysis revealed that the SOS score (p<.001) and lobular inflammation (p=.044) were independently correlated with the liver SWV. Liver SWV is elevated in SOS in proportion to the degree of sinusoidal injury and lobular inflammation in rat SOS models. ARFI elastography has potential as an examination for diagnosis, severity assessment and follow-up of SOS. • Liver SWV using ARFI elastography was significantly elevated in SOS rat. • Sinusoidal injury and lobular inflammation grades had correlation with liver SWV. • ARFI elastography has potential for diagnosis, severity assessment, and follow-up of SOS.

Hitting the snooze button: Inducing quiescence with the FLT3 inhibitor quizartinib protects hematopoietic progenitors from chemotherapy

ABSTRACTMyelosuppression is one of the most severe and limiting side effects of chemotherapy. Our recent work outlines a strategy to prevent chemotherapy-induced myelosuppression by administering a priming dose of the FMS-Like Tyrosine kinase 3 (FLT3) inhibitor quizartinib. Furthermore, by administering sequential quizartinib primed injections of fluorouracil (5-FU), we demonstrated a novel and effective strategy to eliminate disease in two mouse models of quizartinib resistant acute myeloid leukemia (AML).

006 Symptomatic Improvement of Keloid with 5-Fluorouracil Injections

006 Symptomatic Improvement of Keloid with 5-Fluorouracil Injections

The «in vivo» study of blood 5-fluorouracil content by quenching of intrinsic protein fluorescence

The dynamics of blood fluorescence (FL) after intravenous injection of 5-fluorouracil (FU) to oncology patients taking chemotherapy were investigated. It was demonstrated that FU quenches FL of water solutions of tryptophan (Trp) (total concentration is 1.0 × 10−5molL−1, λmax = 353nm) and plasma protein – albumin (λmax = 340nm) with the Stern–Volmer constants 16.4 × 103Lmol−1 and 52Lmol−1, accordingly. The quenching of both Trp and albumin FL by 5-fluorouracil was concluded to proceed via the static mechanism of reversible photoinduced electron transfer (PET).

Phytochemical remedies: a key strategy towards reversing the aggressive murine colon cancer

Colon cancer accounts for about 500,000 death cases worldwide annually and represents approximately 6.5% of cancers in Egypt. This study employed a murine colon cancer model to identify the mechanism of the therapeutic value of gallic acid or ellagic acid against colon carcinogenesis in vivo. Fifty adult male rats were distributed into five groups. Group (1) was set as a negative control group. Groups (2), (3), (4), and (5) were intrarectally injected with N-methylnitrosourea to induce colon cancer. Group (2) was kept untreated, whereas group (3) and (4) were orally administered gallic acid and ellagic acid, respectively. Group (5) received intraperitoneal injection of 5-fluorouracil. The administration of gallic acid, ellagic acid or 5-fluorouracil harmonized the hazardous effect of N-methylnitrosourea in colon cancer-afflicted rats. This was evidenced by the significant depletion in both of serum tumor associated glycoprotein-72 (TAG72) and galectin-3 (GAL3) levels as well as the significant downregulation in the expression level of frizzled-8 receptor (FRZ-8) gene and significant amplification of adenomatous polyposis coli gene expression level in the colon tissues of all treated groups. Intriguingly, such treatments resulted in a notable improvement in the pathological features of colon tissue sections of N-methylnitrosourea-challenged rats. Generally speaking, the current investigation emphasizes the favorable impact of gallic acid and ellagic acid in monitoring the progression of colon cancer in vivo. We suggest that the mitigation of Wnt signaling pathway may be the probable mechanism by which these compounds can offer their therapeutic actions against colon cancer.

Chemotherapy Induces Oral Mucositis in Mice Without Additional Noxious Stimuli

Oral mucositis (OM) is a serious side effect of cancer chemotherapy. The pathobiology of oral mucositis remains incompletely understood due to lack of appropriate models which recapitulate the human condition. Existing rodent models are intraperitoneal and require radiation, chemical or mechanical injury to the chemotherapy protocol to induce oral lesions. We aimed to develop an OM mouse model that is induced solely by chemotherapy and reproduces macroscopic, histopathologic and inflammatory characteristics of the human condition. Female C57BL/6 mice were given intravenous 5-Fluorouracil (5-FU) injections every 48 hours, for 2 weeks. A high daily dose of intraperitoneal administration was tested for comparison. Mice were monitored daily for weight loss. Epithelial histomorphometric analyses in tongue, esophageal and intestinal tissues were conducted coupled with assessment of apoptosis, cell proliferation, neutrophilic infiltration and the integrity of adherens junctions by immunohistochemistry. Neutropenia was assessed in peripheral blood and bone marrow. Tissues were analyzed for pro-inflammatory cytokines at the protein and mRNA levels. Daily intraperitoneal administration of 5-FU led to rapid weight loss and intestinal mucositis, but no oral inflammatory changes. Intravenous administration triggered atrophy of the oral and esophageal epithelium accompanied by reduction in cell proliferation and increased apoptosis. Coincidental with these changes were up-regulation of NF-κB, TNFα, IL-1β, GM-CSF, IL-6 and KC. Despite neutropenia, increased oral neutrophilic infiltration and reduced E-cadherin was observed in oroesophageal mucosae. We developed a novel experimental tool for future mechanistic studies on the pathogenesis of chemotherapy-induced OM.

Preparation of 5-fluorouracil-loaded chitosan nanoparticles and study of the sustained release in vitro and in vivo

The sustained-release properties of the biodegradable nano-drug delivery systems were used to improve the residence time of the chemotherapeutic agent in the body. These drug delivery systems were widely used to deliver chemotherapeutic drugs. The 5-fluorouracil loaded chitosan nanoparticles prepared in this paper have the above advantage. Here, we found that when the mass ratio of 5-fluorouracil and chitosan was 1:1, the maximum drug loading of nanoparticles was 20.13 ± 0.007%, the encapsulation efficiency was 44.28 ± 1.69%, the particle size was 283.9 ± 5.25 nm and the zeta potential was 45.3 ± 3.23 mV. The prepared nanoparticles had both burst-release and sustained-release phases in vitro release studies. In addition, the inhibitory effect of the prepared nanoparticles on gastric cancer SGC-7901 cells was similar to that of 5-fluorouracil injection, and the blank vector had no obvious inhibitory effect on SGC-7901 cells. In the pharmacokinetic study of rats in vivo, we found that AUC (0−t), MRT (0−t) and t1/2z of nanoparticles were significantly increased in vivo compared with 5-fluorouracil solution, indicating that the prepared nanoparticles can play a role in sustained-release.

Use of subconjunctival injections of 5-fluorouracil to rescue and prolong intraocular pressure reduction for a failing Ahmed glaucoma implant.

5-Fluorouracil (5-FU) has been well described for a failing trabeculectomy bleb, but not for aqueous shunts. We sought to determine whether subconjunctival 5-FU prolongs the intraocular pressure (IOP) efficacy of Ahmed shunts. We included all patients with Ahmed FP-7 implantation by one surgeon at Yale University. Patients with <3months follow-up were excluded. Injections were done on a case-by-case basis, usually for IOP > 21 on >2 medications. Five-milligram (0.1cc) injections were made over the plate. The control group consisted of Ahmed FP-7 patients without injections. The main outcome measure was IOP. Secondary outcome was success (IOP <21mmHg, 20% decrease from preoperative IOP, and no reoperation). The average age of controls was 72.5 ± 16.6years, and 63.7 ± 18.8 with 5-FU (p = 0.02). Forty-four patients received 5-FU and 45 did not. Mean preoperative IOP in controls was 31.5 ± 11mmHg on 3.1 ± 1 medications, and 31.9 ± 9.0mmHg (p = 0.86) on 3.3 ± 0.9 medications with 5-FU (p = 0.18). At a mean 137days after surgery, mean pre-injection IOP was 25.3 ± 7.7mmHg on 2.0 ± 1.3 medications. Five years following implantation, control IOPs averaged 12.9 ± 7.1mmHg (53% decrease from preoperative IOP, p < 0.001) on 1.4 ± 1.1 medications versus 17.2 ± 4.9mmHg (46% decrease from preoperative, 32% decrease from pre-5FU IOP, p < 0.001) on 2.7 ± 0.8 medications with 5-FU. The IOP at 5years was statistically similar in both groups (p = 0.23). Five-year success rates trended higher with 5-FU (77 vs. 67%, p = 0.38). Subconjunctival injection of 5-FU sustained a significant long-term decline in intraocular pressures in eyes with failing Ahmed shunts. Outcomes between eyes receiving injections and controls were statistically similar.

Triamcinolone Acetonide and 5-Fluorouracil Intralesional Combination Injection in Keloid Treatment

Objective: To evaluate the effectiveness of steroid and 5-fluorouracil (5-FU) injection combination for keloid management. Methods: A 22-year-old female patient was presented with recurrent skin lesions. The skin lesions first appeared 10 years prior to consultation, had been surgically excised, and were given triamcinolone acetonide injection. However, no improvement was observed. A decision was made to use and evaluate treatment using an intralesional 4 mg (0.1 ml of 40 mg/ml) triamcinolone acetonide and 45 mg (0.9 ml of 50 mg/ml ) 5-FU injection combination for 5 weeks. Results: Clinical improvements were observed in the third week as the lesions softened and pruritic sensation dinimished. At the end of the fifth week, improvements in the form of keloid lesion flattening and size reduction were observed. Conclusions: Intralesional injection using a combination of triamcinolone acetonide and 5-fluorouracil is effective for keloid lesion treatment. Keywords: 5-fluorouracil, intralesional injection, keloid, triamcinolone acetonide DOI: 10.15850/ijihs.v5n1.959

Efficacy and safety of preoperative IOP reduction using a preservative-free fixed combination of dorzolamide/timolol eye drops versus oral acetazolamide and dexamethasone eye drops and assessment of the clinical outcome of trabeculectomy in glaucoma.

IntroductionTo demonstrate that preoperative treatment for 28 days with topical dorzolamide/timolol is non-inferior (Δ = 4 mm Hg) to oral acetazolamide and topical dexamethasone (standard therapy) in terms of intraocular pressure (IOP) reduction 3 and 6 months after trabeculectomy in glaucoma patients.Materials and methodsSixty-two eyes undergoing trabeculectomy with mitomycin C were included in this monocentric prospective randomized controlled study. IOP change between baseline and 3 months post-op was defined as the primary efficacy variable. Secondary efficacy variables included the number of 5-fluorouracil (5-FU) injections, needlings, suture lyses, preoperative IOP change, hypertension rate and change of conjunctival redness 3 and 6 months post-op. Safety was assessed based on the documentation of adverse events.ResultsPreoperative treatment with topical dorzolamide/timolol was non-inferior to oral acetazolamide and topical dexamethasone in terms of IOP reduction 3 months after trabeculectomy (adjusted means -8.12 mmHg versus -8.30 mmHg; Difference: 0.18; 95% CI -1.91 to 2.26, p = 0.8662). Similar results were found 6 months after trabeculectomy (-9.13 mmHg versus -9.06 mmHg; p = 0.9401). Comparable results were also shown for both groups concerning the classification of the filtering bleb, corneal staining, and numbers of treatments with 5-FU, needlings and suture lyses. More patients reported AEs in the acetazolamide/dexamethasone group than in the dorzolamide/timolol group.DiscussionPreoperative, preservative-free, fixed-dose dorzolamide/timolol seems to be equally effective as preoperative acetazolamide and dexamethasone and has a favourable safety profile.

Safety and efficacy of lobaplatin combined with 5-fluorouracil as first-line induction chemotherapy followed by lobaplatin-radiotherapy in locally advanced nasopharyngeal carcinoma: preliminary results of a prospective phase II trial

BackgroundDue to improvements in imaging and radiological techniques as well as the use of chemotherapy, distant metastasis has become the predominant mode of treatment failure in patients with locally advanced nasopharyngeal carcinoma (LA-NPC). Platinum-based systemic chemotherapy has shown survival benefits and is now the standard strategy for systemic therapy in patients with LA-NPC. Notably, the third-generation platinum reagent lobaplatin has shown anti-tumor effects in several solid tumors with lower incidences of gastrointestinal, hepatic and renal toxicity relative to other platinum drugs. However, the safety and efficacy of lobaplatin as a first-line regimen in patients with LA-NPC are undetermined.MethodsPatients with stage III–IVa-b NPC received lobaplatin at a dose of 30 mg/m2 on days 1 and 22 combined with a continuous 120-h intravenous injection of 5-fluorouracil at a dose of 4 g/m2 followed by lobaplatin at a dose of 50 mg/m2 on days 43 and 64 concomitant with intensity-modulated radiation therapy. Objective response rates and acute toxicity were assessed based on RECIST (1.1) and CTCAE v.3.0, respectively. Kaplan-Meier analysis was used to calculate survival rates.ResultsFifty-nine patients were enrolled, and 44 patients (74.6%) received allocated cycles of chemotherapy. The objective response rates were 88.1% (95% confidence interval [CI], 0.77 to 0.95) and 100% after induction chemotherapy (ICT) and concurrent chemoradiotherapy (CRT), respectively. With a median follow-up period of 44 months, the 3-year estimated progression-free survival and overall survival were 86.4% (95% CI, 69.8 to 98.8) and 94.9% (95% CI, 89.5 to 100), respectively. The most common grade 3–4 toxicities were neutropenia (8.5%) and thrombocytopenia (40.7%) after ICT and CRT, respectively.ConclusionLobaplatin combined with 5-fluorouracil followed by lobaplatin-RT treatment showed encouraging anti-tumor effects with tolerable toxicities in patients with LA-NPC. Randomized controlled trials of lobaplatin in patients with LA-NPC are warranted.Trial registrationThis trial was registered with the Chinese Clinical Trials Registry and approved on March 31st, 2012, number ChiCTR-ONC-12002060.