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

Abstract

PURPOSE:

We 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 METHODS:

Twenty-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.

RESULTS:

The 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 AUC(0-inf) of the metabolite mesna was approximately 6.3% of the AUC(0-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.

CONCLUSIONS:

The 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.

• Authors: Noriyuki Masuda, Shunichi Negoro, Frederick Hausheer, Kazuhiko Nakagawa, Kaoru Matsui, Shinzoh Kudoh, Koji Takeda, Nobuyuki Yamamoto, Naruo Yoshimura, Yasuo Ohashi, Masahiro Fukuoka
• Journal: Cancer chemotherapy and pharmacology (Cancer Chemother Pharmacol) Vol. 67 Issue 3 Pg. 533-42 (Mar 2011) ISSN: 1432-0843 [Electronic] Germany
• PMID: 20473611 (Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 2,2'-dithiodiethanesulfonic acid
• Mesna
• Paclitaxel
• Cisplatin

Topics

• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, pharmacokinetics, pharmacology)
• Area Under Curve
• Carcinoma, Non-Small-Cell Lung (drug therapy, pathology)
• Cisplatin (administration & dosage)
• Dose-Response Relationship, Drug
• Female
• Humans
• Lung Neoplasms (drug therapy, pathology)
• Male
• Mesna (adverse effects, analogs & derivatives, pharmacokinetics, pharmacology)
• Middle Aged
• Neoplasm Staging
• Paclitaxel (administration & dosage)
• Treatment Outcome