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01.01.2010 | Original Article

Phase 1 first-in-human clinical study of S-trans, trans-farnesylthiosalicylic acid (salirasib) in patients with solid tumors

verfasst von: Apostolia Maria Tsimberidou, Michelle A. Rudek, David Hong, Chaan S. Ng, Jessica Blair, Howard Goldsweig, Razelle Kurzrock

Erschienen in: Cancer Chemotherapy and Pharmacology | Ausgabe 2/2010

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Abstract

Purpose

This phase I first-in-human trial evaluated salirasib, an S-prenyl derivative of thiosalicylic acid that competitively blocks RAS signaling.

Methods

Patients with advanced cancers received salirasib twice daily for 21 days every 4 weeks. Doses were escalated from 100 to 200, 400, 600, and 800 mg.

Results

The most common toxicity was dose-related diarrhea (Grade 1–2, 79% of 24 patients). Other toxicities included abdominal pain, nausea, and vomiting. No Grade 3–4 toxicity was noted. Nineteen (79%) patients had no drug-related toxicity >Grade 1. Dose-limiting toxicity (DLT) was not reached, but all three patients treated with 800 mg experienced Grade 1–2 diarrhea, abrogating dose escalation. Six patients were treated at a dose of 600 mg with no DLTs. Seven (29%) patients had stable disease on salirasib for ≥4 months (range 4–23+). The salirasib pharmacokinetic profile was characterized by slow absorption and a rapid elimination phase following oral administration. Salirasib exposure (C _max; day 1 AUC_inf vs. day 15 AUC_0–12 h) was similar between days 1 and 15 (P > 0.05). The T _1/2 (mean ± SD) was 3.6 ± 2.2 h on day 1.

Conclusions

Salirasib therapy was well tolerated. The recommended dose for phase II studies is 600 mg twice daily.

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Titel: Phase 1 first-in-human clinical study of S-trans, trans-farnesylthiosalicylic acid (salirasib) in patients with solid tumors
verfasst von: Apostolia Maria Tsimberidou
Michelle A. Rudek
David Hong
Chaan S. Ng
Jessica Blair
Howard Goldsweig
Razelle Kurzrock
Publikationsdatum: 01.01.2010
Verlag: Springer-Verlag
Erschienen in: Cancer Chemotherapy and Pharmacology / Ausgabe 2/2010
Print ISSN: 0344-5704
Elektronische ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-009-1027-4

Springer Medizin

Phase 1 first-in-human clinical study of S-trans, trans-farnesylthiosalicylic acid (salirasib) in patients with solid tumors