Abstract
Giroline (RP 49532A) is a new protein-synthesis inhibitor with broad antitumor activity in experimental models. In the present phase I study, Giroline was given by 24-h i.v. infusion every 3 weeks at doses ranging from 3 to 15 mg/m2 to 12 patients with advanced refractory solid tumors. The dose-limiting toxic effects were delayed hypotension and severe asthenia. The maximum tolerated dose (MTD) was 15 mg/m2. Transient nausea and vomiting during infusion were reported at all dose levels. Mild reversible prolongation of prothrombin time and activated partial thromboplastin time was observed in most patients at dose levels above 3 mg/m2. No antitumor activity was observed. The toxicity profile of Giroline precludes further evaluation in cancer patients.
Similar content being viewed by others
References
Ahond A, Bedoya Zurita M, Colin M, Fizames C, Laboute P, Lavelle F, Laurent D, Poupat C, Pusset J, Thoison O, Potier P (1988) La Giroline, nouvelle substance antitumorale extraite de l'èpongePseudaxinyssa cantharella. C R Acad Sci [III] 307: 145–148
Alakl M, Armand JP, Gandia D, Le Bail N, Bayssas M, Chevalier P, Carde P, Escudier B, Recondo G (1991) Phase I and pharmacokinetics of RP 49532: Giroline in cancer patients. Proc Am Assoc Cancer Res 10: 310
Carter SK (1977) Clinical trials in cancer chemotherapy. Cancer 40: 544–557
Lavelle F, Fizames C, Ahond A, Poupat C, Curaudeau A (1989) Experimental properties of RP 49532, a new antitumor marine compound. Proc Am Assoc Cancer Res 30: 583
Lavelle F, Zerial A, Fizames C, Rabault B, Curaudeau A (1991) Antitumor activity and mechanism of action of the marine compound girodazole. Invest New Drugs 9: 233–244
NCI Division of Cancer Treatment (1988). NCI toxicity criteria. National Cancer Institute, Bethesda, Maryland
Schneidermann MA (1966) Mouse to man: statistical problems in bringing a drug to clinical trial In: Proceedings of the 5th Berkeley Symposium on Mathematical Statistics and Probability University of California Press, Berkeley, pp 855–866
World Health Organization (1979) Handbook for reporting results of cancer treatment. Offset publication 48. WHO, Geneva
Author information
Authors and Affiliations
Additional information
This work is dedicated to the memory of Prof. Michel Clavel
Rights and permissions
About this article
Cite this article
Catimel, G., Coquard, R., Guastalla, J.P. et al. Phase I study of RP 49532A, a new protein-synthesis inhibitor, in patients with advanced refractory solid tumors. Cancer Chemother. Pharmacol. 35, 246–248 (1995). https://doi.org/10.1007/BF00686555
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00686555