A phase 1/1b study of satraplatin (JM-216) in combination with docetaxel in patients with advanced solid tumors and metastatic castrate-resistant prostate cancer

Abstract Background Satraplatin is an oral platinum with potential advantages over other platinum agents. This study investigated the combination of satraplatin and docetaxel in a phase 1 study of patients with advanced solid tumor malignancies followed by a phase 1b study in men with chemotherapy n...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Urologic oncology 2013-05, Vol.31 (4), p.436-441
Hauptverfasser: Cetnar, Jeremy, M.D, Wilding, George, M.D, McNeel, Douglas, M.D., Ph.D, LoConte, Noelle K., M.D, McFarland, Thomas A., M.D, Eickhoff, Jens, Ph.D, Liu, Glenn, M.D
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung:Abstract Background Satraplatin is an oral platinum with potential advantages over other platinum agents. This study investigated the combination of satraplatin and docetaxel in a phase 1 study of patients with advanced solid tumor malignancies followed by a phase 1b study in men with chemotherapy naïve metastatic castrate-resistant prostate cancer (CRPC). Methods In this single institution phase 1/1b study, patients received docetaxel on day 1 and satraplatin on days 1–5 of a 21-day cycle ± granulocyte colony stimulating factor (GCSF). For phase 1b, prednisone 10 mg daily was added. Results Twenty-nine patients received treatment. Based on 3 dose limiting toxicities (DLT) (grade 4 neutropenia) in 13 patients at dose levels 1 and −1 (docetaxel 60 mg/m2 plus satraplatin 40 mg/m2 and docetaxel 60 mg/m2 plus satraplatin 50 mg/m2 ) GCSF was administered with subsequent cohorts. A dose level of docetaxel 60 mg/m2 plus satraplatin 50 mg/m2 with GCSF was the starting dose level for phase 1b. At the highest dose in the phase 1b (docetaxel 75 mg/m2 plus satraplatin 50 mg/m2 ) there were no DLTs. Conclusion The combination of satraplatin and docetaxel is feasible in solid tumor malignancies. In advanced malignancies, the recommended phase 2 dose is docetaxel 60 mg/m2 IV day 1 with satraplatin 40 mg/m2 /d PO days 1–5, without G-CSF, and Docetaxel 70 mg/m2 IV day 1 with Satraplatin 50 mg/m2 /day PO days 1–5, with G-CSF support, repeated in 3-week cycles. For patients with CRPC the recommended phase 2 dose is docetaxel 75 mg/m2 IV day 1 with satraplatin 50 mg/m2 /d PO days 1–-5, with G-CSF and prednisone 10 mg daily, repeated in 3-week cycles.
ISSN:1078-1439
1873-2496
DOI:10.1016/j.urolonc.2011.02.007