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

Noriyuki Masuda, Shunichi Negoro, Frederick Hausheer, Kazuhiko Nakagawa, Kaoru Matsui, Shinzoh Kudoh, Koji Takeda, Nobuyuki Yamamoto, Naruo Yoshimura, Yasuo Ohashi, Masahiro Fukuoka

Research output: Contribution to journalArticle

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/m 2 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.

Original languageEnglish (US)
Pages (from-to)533-542
Number of pages10
JournalCancer Chemotherapy and Pharmacology
Volume67
Issue number3
DOIs
StatePublished - Mar 2011
Externally publishedYes

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Non-Small Cell Lung Carcinoma
Paclitaxel
Cells
Cisplatin
Mesna
Toxicity
Area Under Curve
2,2'-dithiodiethanesulfonic acid
Thirst
Pharmacokinetics
Chemotherapy
Metabolites
TP protocol
Exanthema
Antineoplastic Agents
Nausea
Skin
Drug Therapy

Keywords

  • BNP7787
  • Chemoprotector
  • Lung cancer
  • Mesna
  • Phase I study

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Pharmacology
  • Pharmacology (medical)
  • Toxicology

Cite this

Phase i and pharmacologic study of BNP7787, a novel chemoprotector in patients with advanced non-small cell lung cancer. / Masuda, Noriyuki; Negoro, Shunichi; Hausheer, Frederick; Nakagawa, Kazuhiko; Matsui, Kaoru; Kudoh, Shinzoh; Takeda, Koji; Yamamoto, Nobuyuki; Yoshimura, Naruo; Ohashi, Yasuo; Fukuoka, Masahiro.

In: Cancer Chemotherapy and Pharmacology, Vol. 67, No. 3, 03.2011, p. 533-542.

Research output: Contribution to journalArticle

Masuda, N, Negoro, S, Hausheer, F, Nakagawa, K, Matsui, K, Kudoh, S, Takeda, K, Yamamoto, N, Yoshimura, N, Ohashi, Y & Fukuoka, M 2011, 'Phase i and pharmacologic study of BNP7787, a novel chemoprotector in patients with advanced non-small cell lung cancer', Cancer Chemotherapy and Pharmacology, vol. 67, no. 3, pp. 533-542. https://doi.org/10.1007/s00280-010-1340-y
Masuda, Noriyuki ; Negoro, Shunichi ; Hausheer, Frederick ; Nakagawa, Kazuhiko ; Matsui, Kaoru ; Kudoh, Shinzoh ; Takeda, Koji ; Yamamoto, Nobuyuki ; Yoshimura, Naruo ; Ohashi, Yasuo ; Fukuoka, Masahiro. / Phase i and pharmacologic study of BNP7787, a novel chemoprotector in patients with advanced non-small cell lung cancer. In: Cancer Chemotherapy and Pharmacology. 2011 ; Vol. 67, No. 3. pp. 533-542.
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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/m 2 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.",
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AU - Hausheer, Frederick

AU - Nakagawa, Kazuhiko

AU - Matsui, Kaoru

AU - Kudoh, Shinzoh

AU - Takeda, Koji

AU - Yamamoto, Nobuyuki

AU - Yoshimura, Naruo

AU - Ohashi, Yasuo

AU - Fukuoka, Masahiro

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