Phase I and clinical pharmacological evaluation of pirozantrone hydrochloride (oxantrazole)

Matthew M. Ames, Charles Lawrence Loprinzi, Jerry M. Collins, Carol Van Haelst-Pisani, Ronald L. Richardson, Joseph Rubin, Charles G. Moertel

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Pirozantrone hydrochloride, an anthrapyrazole analogue, was selected for clinical evaluation based on broad antitumor activity against murine tumor systems and on potentially less cardiotoxicity when compared to anthracyclines. This anthrapyrazole analogue is currently under clinical evaluation, and we now report results on a Phase I clinical trial incorporating a pharmacologically guided dose-escalation scheme. Dose escalation was designed to proceed by factors of 2 until the patient drug exposure (concentration x time) was 40% of the murine exposure at the LD10 dose (90 mg/m2). Thereafter, more moderate dose escalations were employed. The target concentration x time value (59 μg-min/ml) derived from preclinical pharmacology data was exceeded in all three patients at a dose of 90 mg/m2. A dose of 160 mg/m2 was found to reproducibly result in appropriate myelosuppression. This dose is recommended for further testing in Phase II studies. Nonhematological toxicities encountered in this trial were mild, the most notable being phlebitis at the infusion site. Objective responses were observed in two patients, one with metastatic breast cancer and another with metastatic melanoma. Following a 60-min infusion, pirozantrone hydrochloride plasma elimination was monoexponential, with a half-life of approximately 30 min, mean total body clearance of 1.29 liters/min/m2, and mean steady state volume of distribution of 29 liters/m2.

Original languageEnglish (US)
Pages (from-to)3905-3909
Number of pages5
JournalCancer Research
Volume50
Issue number13
StatePublished - Jul 1 1990

Fingerprint

piroxantrone
Pharmacology
Phlebitis
Clinical Trials, Phase I
Anthracyclines
Half-Life
Melanoma
Breast Neoplasms
Pharmaceutical Preparations
Neoplasms

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Ames, M. M., Loprinzi, C. L., Collins, J. M., Van Haelst-Pisani, C., Richardson, R. L., Rubin, J., & Moertel, C. G. (1990). Phase I and clinical pharmacological evaluation of pirozantrone hydrochloride (oxantrazole). Cancer Research, 50(13), 3905-3909.

Phase I and clinical pharmacological evaluation of pirozantrone hydrochloride (oxantrazole). / Ames, Matthew M.; Loprinzi, Charles Lawrence; Collins, Jerry M.; Van Haelst-Pisani, Carol; Richardson, Ronald L.; Rubin, Joseph; Moertel, Charles G.

In: Cancer Research, Vol. 50, No. 13, 01.07.1990, p. 3905-3909.

Research output: Contribution to journalArticle

Ames, MM, Loprinzi, CL, Collins, JM, Van Haelst-Pisani, C, Richardson, RL, Rubin, J & Moertel, CG 1990, 'Phase I and clinical pharmacological evaluation of pirozantrone hydrochloride (oxantrazole)', Cancer Research, vol. 50, no. 13, pp. 3905-3909.
Ames MM, Loprinzi CL, Collins JM, Van Haelst-Pisani C, Richardson RL, Rubin J et al. Phase I and clinical pharmacological evaluation of pirozantrone hydrochloride (oxantrazole). Cancer Research. 1990 Jul 1;50(13):3905-3909.
Ames, Matthew M. ; Loprinzi, Charles Lawrence ; Collins, Jerry M. ; Van Haelst-Pisani, Carol ; Richardson, Ronald L. ; Rubin, Joseph ; Moertel, Charles G. / Phase I and clinical pharmacological evaluation of pirozantrone hydrochloride (oxantrazole). In: Cancer Research. 1990 ; Vol. 50, No. 13. pp. 3905-3909.
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