Leukopoiesis Is Not Affected after Intravenous Treatment with the Novel Antineoplastic Agent Taurolidine

Braumann, Chris; Menenakos, Charalambos; Atanassov, Vladimir; Pfirrmann, R. W.; Guenther, Nina; Jacobi, C. A.

doi:10.1159/000118030

Cited by 7 publications

(11 citation statements)

References 31 publications

(13 reference statements)

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“…However, previous experimental studies with tumor load showed no influence of TRD in hemopoiesis, renal and liver function which are commonly affected by usual chemotherapeutics [5,8,30] .…”

Section: Discussionmentioning

confidence: 85%

“…Moreover, after intraoperative use the overall side effects were not relevant in animal experiments [20] , and hemopoiesis was not inhibited [8] . This might be explained by a selective molecular mechanism [7] .…”

Section: Discussionmentioning

confidence: 97%

“…The biochemical properties of the antitumorigenic agent have been described in detail elsewhere [7,8] . Only clinically relevant concentrations were examined.…”

Section: Taurolidinementioning

confidence: 99%

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Wound Healing Is Not Impaired in Rats Undergoing Perioperative Treatment with the Antineoplastic Agent Taurolidine

Braumann

Guenther²,

Pohlenz³

et al. 2008

Eur Surg Res

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Background/Aim: The aim of this study was to determine whether an intravenous or an intraperitoneal application of the antineoplastic agent taurolidine (TRD) impairs wound healing in the absence of tumor load in rats. Methods: Eighty rats were randomized into eight groups (n = 10). Median laparotomy was performed in all animals. Three groups were treated by intravenous injection and three groups by local administration using a central port catheter system. For each group, 1 ml was applied: isotone sodium chloride solution (control groups), 1% TRD, 2% TRD, and 3% TRD. Fascia and skin were closed using a standardized running suture technique with 4-0 Vicryl®. Wounds were evaluated once a day. Animals were treated every 8 h for 7 days (ports were then removed) and wounds were evaluated at day 28. Macroscopic and histopathologic examinations of scar tissue biopsies (hemalaun-eosin stain) were performed at the end of the experiment. Results: No animal died. No relevant impairment of wound healing was observed independent of the different treatment strategies. Conclusion: Our results suggest that wound healing does not seem to be impaired by TRD in rats.

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Section: Discussionmentioning

confidence: 85%

Section: Discussionmentioning

confidence: 97%

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Wound Healing Is Not Impaired in Rats Undergoing Perioperative Treatment with the Antineoplastic Agent Taurolidine

Braumann

Guenther²,

Pohlenz³

et al. 2008

Eur Surg Res

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“…In this study, we decided to use the concentration as described in human standard therapy and suitable for intravenous (i.v.) injections and other animal studies with comparable total doses (28,29). We decided to use the commercially available ready-to-use TRD 2% solution, which has been already used in human i.v.…”

Section: Discussionmentioning

confidence: 99%

Divergent effects of taurolidine as potential anti-neoplastic agent: Inhibition of bladder carcinoma cells in vitro and promotion of bladder tumor in vivo

Abramjuk

Bueschges²,

Schnorr³

et al. 2009

Oncol Rep

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Abstract. We investigated taurolidine (TRD) against various human bladder cell lines and the AY-27 rat bladder carcinoma cells. In vitro we tested the effect of TRD in ascending concentrations depending on different incubation times on cell proliferation by the XTT-test. Taurolidine had an inhibitory effect on all tested cell lines. Increasing concentrations and longer incubation times decreased the proliferation depending on the primary quantities of cells. For in vivo studies, an orthotopic rat bladder carcinoma was used. The animals were treated intravenously or intravesically and the tumors were harvested and weighted after the study. In contrast to other authors we could not find any anti-proliferative effect, we actually showed that instillation into the rat urinary bladder enhanced tumor growth.

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“…A bone marrow aspirate determined that the lower neutrophil count was not due to bone marrow suppression. In a study in rats, the administration of taurolidine did not affect leucopoiesis [29]. The dog was monitored daily for over 3.5 years after the administration of taurolidine and remained healthy.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetic study and evaluation of the safety of taurolidine for dogs with osteosarcoma

Marley

Helfand

Simpson

et al. 2013

J Exp Clin Cancer Res

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BackgroundOsteosarcoma in dogs and humans share many similarities and the dog has been described as an excellent model to study this disease. The median survival in dogs has not improved in the last 25 years. Taurolidine has been shown to be cytotoxic to canine and human osteosarcoma in vitro. The goals of this study were to determine the pharmacokinetics and safety of taurolidine in healthy dogs and the safety of taurolidine in combination with doxorubicin or carboplatin in dogs with osteosarcoma.MethodsTwo percent taurolidine was infused into six healthy dogs (150 mg/kg) over a period of two hours and blood samples were taken periodically. One dog received taurolidine with polyvinylpyrrolidone (PVP) as its carrier and later received PVP-free taurolidine as did all other dogs in this study. Serum taurolidine concentrations were determined using high-performance liquid chromatography (HPLC) online coupled to ESI-MS/MS in the multiple reaction monitoring mode. Subsequently, the same dose of taurolidine was infused to seven dogs with osteosarcoma also treated with doxorubicin or carboplatin.ResultsTaurolidine infusion was safe in 6 healthy dogs and there were no significant side effects. Maximum taurolidine serum concentrations ranged between 229 to 646 μM. The dog that received taurolidine with PVP had an immediate allergic reaction but recovered fully after the infusion was stopped. Three additional dogs with osteosarcoma received doxorubicin and taurolidine without PVP. Toxicities included dilated cardiomyopathy, protein-losing nephropathy, renal insufficiency and vasculopathy at the injection site. One dog was switched to carboplatin instead of doxorubicin and an additional 4 dogs with osteosarcoma received taurolidine-carboplatin combination. One incidence of ototoxicity occurred with the taurolidine- carboplatin combination. Bone marrow and gastro-intestinal toxicity did not appear increased with taurolidine over doxorubicin or carboplatin alone.ConclusionsTaurolidine did not substantially exacerbate bone marrow or gastro-intestinal toxicity however, it is possible that taurolidine increased other toxicities of doxorubicin and carboplatin. Administering taurolidine in combination with 30 mg/m2 doxorubicin in dogs is not recommended but taurolidine in combination with carboplatin (300 mg/m2) appears safe.

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Leukopoiesis Is Not Affected after Intravenous Treatment with the Novel Antineoplastic Agent Taurolidine

Cited by 7 publications

References 31 publications

Wound Healing Is Not Impaired in Rats Undergoing Perioperative Treatment with the Antineoplastic Agent Taurolidine

Wound Healing Is Not Impaired in Rats Undergoing Perioperative Treatment with the Antineoplastic Agent Taurolidine

Divergent effects of taurolidine as potential anti-neoplastic agent: Inhibition of bladder carcinoma cells in vitro and promotion of bladder tumor in vivo

Pharmacokinetic study and evaluation of the safety of taurolidine for dogs with osteosarcoma

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