Phase I and pharmacologie study of the arotinoid Ro 40-8757 in combination with cisplatin and etoposide in patients with non-small cell lung cancer

Lia Van Zuylen*, Jan H.M. Schellens, Swan H. Goey, Linda C. Pronk, Maureen M. De Boer-Dennert, Walter J. Loos, Jianguo Ma, Gerrit Stoter, Jaap Verweij

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

This phase I study was performed to assess the feasibility of combining cisplatin/etoposide (VP-16) with the arotinoid Ro 40-8757 and to determine the dose-limiting toxicity (DLT) of Ro 40-8757 in this combination. Patients with non-small cell lung cancer were eligible. Treatment consisted of Ro 40-8757 p.o. day 1-21, cisplatin 100 mg/m2 i.v. on day 2 and VP-16 100 mg/m2 i.v. on day 2-4, repeated every 3 weeks. Eighteen patients were évaluable for toxicity and response. The doses of Ro 40-8757 ranged from 84 mg/m2 once daily to 42 mg/m2 thrice daily (tid). DLT consisting of delayed nausea/vomiting was reached at 42 mg/m2 tid. Consequently, the maximum tolerated dose was set at one dose level below the DLT, i.e. 28 mg/m2 tid. Skin toxicity occurred but was well manageable. Pharmacological analyses showed a small increase in the volume of distribution of cisplatin and VP-16 between the first and third course. However, no relationship with side effects was found. A response was achieved in 50% of patients. The combination of cisplatin/VP-16 with Ro 40-8757 appears to be feasible at a dose schedule of 28 mg/m2 tid. The response rate was at the upper rate of what can be expected with cisplatin and VP-16. [

Original languageEnglish
Pages (from-to)361-368
Number of pages8
JournalAnti-Cancer Drugs
Volume10
Issue number4
DOIs
Publication statusPublished - 1 Jan 1999
Externally publishedYes

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