Phase I and pharmacologic study of BNP7787, a novel chemoprotector in patients with advanced non-small cell lung cancer

Abstract

PurposeWe conducted a phase I trial of BNP7787 (disodium 2,2′-dithio-bis-ethane sulfonate, Tavocept™), a novel chemoprotective and antitumor enhancing agent administered in combination with paclitaxel and cisplatin. The primary aim was to determine a safe and potentially efficacious BNP7787 dose for preventing and mitigating paclitaxel- and cisplatin-induced toxicities and to evaluate for preliminary evidence of efficacy of treatment.Patients and methodsTwenty-two patients with stage IIIB/IV non-small cell lung cancer (NSCLC) received BNP7787 alone 1 week before co-administration of BNP7787 with paclitaxel followed by cisplatin. Twenty-one patients were treated with BNP7787 in escalating doses of 4.1–41.0 g/m2 concurrently with paclitaxel 175 mg/m2 and cisplatin 75 mg/m2 every 3 weeks.ResultsThe appropriate dose was determined to be 18.4 g/m2 of BNP7787 although no dose-limiting toxicity was observed up to 41.0 g/m2. Mild intravenous site discomfort, thirst, and nausea were the most common toxicities. One patient developed grade 2 skin rash, which was severe enough to preclude further study treatment. The AUC0-inf of the metabolite mesna was approximately 6.3% of the AUC0-inf of BNP7787. Co-administration of paclitaxel and cisplatin did not appear to influence the pharmacokinetics of BNP7787 and mesna. The overall response rate was encouraging; 43% including 11 patients with prior chemotherapy.ConclusionsThe recommended dose for phase II/III studies is 18.4 mg/m2 of BNP7787 in combination with paclitaxel and cisplatin. Further studies are warranted to assess whether BNP7787 prevents and mitigates common and serious paclitaxel- and cisplatin-related side effects and enhances the efficacy of paclitaxel and cisplatin in advanced NSCLC patients.

Can Medical Herbs Stimulate Regeneration or Neuroprotection and Treat Neuropathic Pain in Chemotherapy-Induced Peripheral Neuropathy?

“…A few components which can protect different tissues from toxic agents were clinically tested, showing conflicting results. No conclusive reports confirming their effectiveness have been provided [44, 45] and a reduction of anticancer activity was suspected [46]. Several neurotrophins were tested but there was no evidence of neuroprotection [47–50].…”

Neuropathy Secondary to Chemotherapy: A Real Issue for Cancer Survivors

“…Results, however, were conflicting, and the effectiveness of these agents is inconclusive. Indeed, the use of these agents may actually reduce anticancer activity (Masuda et al, 2011;Moore et al, 2003).…”

“…Studies conducted in human tumour xenografts demonstrated that the agent does not interfere with the efficacy of chemotherapy (Boven et al, 2002). Masuda et al (2011) conducted a phase I trial of BNP7787 (disodium 2,2'-dithio-bis-ethane sulfonate, Tavocept™) primarily to determine its safety and potential efficacy to prevent and mitigate paclitaxel-and cisplatininduced toxicities. Twenty-two patients with stage IIIB/IV non-small-cell lung cancer (NSCLC) received BNP7787 alone one week before co-administration of BNP7787 with paclitaxel followed by cisplatin.…”

Clinical Evaluation of Tavocept to Decrease Diuresis Time and Volume in Dogs with Bladder Cancer Receiving Cisplatin

“…Tavocept is converted to mesna in the kidneys, which then locally inactivates the toxic platinum species . In preclinical studies, Tavocept protected against cisplatin nephrotoxicity in both rats and dogs, and the use of Tavocept before cisplatin in people allows a 75% decrease in fluid diuresis . A similar decrease in fluid diuresis volume requirements would be ideal for dogs at risk of volume overload using the standard cisplatin administration protocol.…”

“…25 In preclinical studies, Tavocept protected against cisplatin nephrotoxicity in both rats and dogs, and the use of Tavocept before cisplatin in people allows a 75% decrease in fluid diuresis. [26][27][28] A similar decrease in fluid diuresis volume requirements would be ideal for dogs at risk of volume overload using the standard cisplatin administration protocol. Tavocept does not contain the free thiol group that could diminish the antitumor effects of cisplatin.…”