Phase I study of ethylenediamine platinum(II) malonate (NSC 146 068), a second generation platinum analogue

B. Winograd, J. B. Vermorken, W. W. Ten Bokkel Huinink, G. Simonetti, H. E. Gall, M. K. Knobf, W. J. van der Vijgh, J. G. McVie, H. M. Pinedo

Research output: Contribution to journalArticle

Abstract

Ethylenediamine platinum(II) malonate [JM-40 (NSC 146 068)] has been selected for clinical studies because of its favorable preclinical toxicity profile as a 'second generation' platinum analogue. When compared to cisplatin, JM-40 was less emetic in the ferret and less nephrotoxic in the dog, while its antitumor activity approached that of cisplatin. Twenty-nine patients received 86 courses of JM-40 as a single dose every 3-4 wk. After 13 dose escalation steps the maximum tolerable dose was reached at 1200 mg/m2. The dose limiting toxicities were nausea, vomiting, and nephrotoxicity. The renal damage seemed reversible up to a dose level of 1000 mg/m2 and consisted of a glomerular and tubular dysfunction. JM-40 did not cause any other dose related side effect or myelo-suppression. Pharmacokinetic studies at a dose of 1000 mg/m2 revealed mean terminal half-lives of 5.0 and 1.9 days for platinum in plasma and plasma ultrafiltrate, respectively. The mean cumulative excretion of platinum in urine accounted for 57% of the dose up to day 5. Two partial responses were observed in a patient with a large cell carcinoma of the lung and in one with a carcinoma of the lacrimal gland. Limited evaluation of JM-40 in phase II studies is warranted. The recommended dose is 1000 mg/m2 every 4 wk and 800 mg/m2 for patients pretreated with platinum analogues.

Original languageEnglish (US)
Pages (from-to)2148-2151
Number of pages4
JournalCancer Research
Volume46
Issue number4 II
StatePublished - 1986
Externally publishedYes

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Platinum
Cisplatin
Emetics
Large Cell Carcinoma
Lacrimal Apparatus
Ferrets
Nausea
Vomiting
ethylenediamine platinum(II) malonate
Pharmacokinetics
Urine
Dogs
Carcinoma
Kidney
Lung

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Winograd, B., Vermorken, J. B., Ten Bokkel Huinink, W. W., Simonetti, G., Gall, H. E., Knobf, M. K., ... Pinedo, H. M. (1986). Phase I study of ethylenediamine platinum(II) malonate (NSC 146 068), a second generation platinum analogue. Cancer Research, 46(4 II), 2148-2151.

Phase I study of ethylenediamine platinum(II) malonate (NSC 146 068), a second generation platinum analogue. / Winograd, B.; Vermorken, J. B.; Ten Bokkel Huinink, W. W.; Simonetti, G.; Gall, H. E.; Knobf, M. K.; van der Vijgh, W. J.; McVie, J. G.; Pinedo, H. M.

In: Cancer Research, Vol. 46, No. 4 II, 1986, p. 2148-2151.

Research output: Contribution to journalArticle

Winograd, B, Vermorken, JB, Ten Bokkel Huinink, WW, Simonetti, G, Gall, HE, Knobf, MK, van der Vijgh, WJ, McVie, JG & Pinedo, HM 1986, 'Phase I study of ethylenediamine platinum(II) malonate (NSC 146 068), a second generation platinum analogue', Cancer Research, vol. 46, no. 4 II, pp. 2148-2151.
Winograd B, Vermorken JB, Ten Bokkel Huinink WW, Simonetti G, Gall HE, Knobf MK et al. Phase I study of ethylenediamine platinum(II) malonate (NSC 146 068), a second generation platinum analogue. Cancer Research. 1986;46(4 II):2148-2151.
Winograd, B. ; Vermorken, J. B. ; Ten Bokkel Huinink, W. W. ; Simonetti, G. ; Gall, H. E. ; Knobf, M. K. ; van der Vijgh, W. J. ; McVie, J. G. ; Pinedo, H. M. / Phase I study of ethylenediamine platinum(II) malonate (NSC 146 068), a second generation platinum analogue. In: Cancer Research. 1986 ; Vol. 46, No. 4 II. pp. 2148-2151.
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AU - Simonetti, G.

AU - Gall, H. E.

AU - Knobf, M. K.

AU - van der Vijgh, W. J.

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