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Phase I study of RP 49532A, a new protein-synthesis inhibitor, in patients with advanced refractory solid tumors
G Catimel1, R Coquard, J P Guastalla
1Department of Medical Oncology, Centre Léon Bérard, Lyon, France.
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.
Insights
Giroline, a novel protein-synthesis inhibitor, showed significant toxicity including hypotension and asthenia in a phase I trial for advanced cancers. Its toxicity profile prevents further clinical evaluation for cancer treatment.
Area of Science:
- Oncology
- Pharmacology
Background:
- Giroline (RP 49532A) is a novel protein-synthesis inhibitor.
- Preclinical studies indicated broad antitumor activity for Giroline.
Purpose of the Study:
- To evaluate the safety and tolerability of Giroline in patients with advanced refractory solid tumors.
- To determine the maximum tolerated dose (MTD) of Giroline.
Main Methods:
- A phase I clinical trial was conducted.
- Giroline was administered via 24-hour intravenous infusion every 3 weeks.
- Doses ranged from 3 to 15 mg/m2 in 12 patients.
Main Results:
- Dose-limiting toxicities included delayed hypotension and severe asthenia.
- The maximum tolerated dose (MTD) was determined to be 15 mg/m2.
- Transient nausea, vomiting, and mild reversible coagulation time prolongation were observed. No antitumor activity was detected.
Conclusions:
- The toxicity profile of Giroline, particularly severe hypotension and asthenia, is unacceptable for further development in cancer patients.
- Giroline is not recommended for further clinical evaluation in oncology due to its adverse effects and lack of efficacy.