Skip to main content
main-content

01.09.2009 | Original Article | Ausgabe 4/2009

Cancer Chemotherapy and Pharmacology 4/2009

Phase I study of bryostatin 1, a protein kinase C modulator, preceding cisplatin in patients with refractory non-hematologic tumors

Zeitschrift:
Cancer Chemotherapy and Pharmacology > Ausgabe 4/2009
Autoren:
Anna C. Pavlick, Jennifer Wu, John Roberts, Mark A. Rosenthal, Anne Hamilton, Scott Wadler, Kathleen Farrell, Michelle Carr, David Fry, Anthony J. Murgo, Ruth Oratz, Howard Hochster, Leonard Liebes, Franco Muggia
Wichtige Hinweise
The work was supported by U01 CA76642, P30 CA 16087 and GCRC MO1 RR00096.

Abstract

Purpose

Preclinical data suggested that bryostatin-1 (bryo) could potentiate the cytotoxicity of cisplatin when given prior to this drug. We designed a phase I study to achieve tolerable doses and schedules of bryo and cisplatin in combination and in this sequence.

Methods

Patients with non-hematologic malignancies received bryo followed by cisplatin in several schedules. Bryo was given as an 1 and a 24 h continuous infusion, while cisplatin was always given over 1 h at 50  and 75 mg/m2; the combined regimen was repeated on an every 3-week and later on an every 2-week schedule. Bryo doses were escalated until recommended phase II doses were defined for each schedule. Patients were evaluated with computerized tomography every 2 cycles.

Results

Fifty-three patients were entered. In an every 2-week schedule, the 1-h infusion of bryo became limited by myalgia that was clearly cumulative. With cisplatin 50 mg/m2 its recommended phase II dose was 30 μg/m2. In the 3-week schedule, dose-limiting toxicities were mostly related to cisplatin effects while myalgias were tolerable. Pharmacokinetics unfortunately proved to be unreliable due to bryo’s erratic extraction. Consistent inhibition of PKC isoform eta (η) in peripheral blood mononuclear cells was observed following bryo.

Conclusions

Bryo can be safely administered with cisplatin with minimal toxicity; however, only four patients achieved an objective response. Modulation of cisplatin cytotoxicity by bryo awaits further insight into the molecular pathways involved.

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

★ PREMIUM-INHALT
e.Med Interdisziplinär

Mit e.Med Interdisziplinär erhalten Sie Zugang zu allen CME-Fortbildungen und Fachzeitschriften auf SpringerMedizin.de. Zusätzlich können Sie eine Zeitschrift Ihrer Wahl in gedruckter Form beziehen – ohne Aufpreis.

Weitere Produktempfehlungen anzeigen
Literatur
Über diesen Artikel

Weitere Artikel der Ausgabe 4/2009

Cancer Chemotherapy and Pharmacology 4/2009 Zur Ausgabe
  1. Das kostenlose Testabonnement läuft nach 14 Tagen automatisch und formlos aus. Dieses Abonnement kann nur einmal getestet werden.

  2. Das kostenlose Testabonnement läuft nach 14 Tagen automatisch und formlos aus. Dieses Abonnement kann nur einmal getestet werden.

Neu im Fachgebiet Onkologie

Mail Icon II Newsletter

Bestellen Sie unseren kostenlosen Newsletter Update Onkologie und bleiben Sie gut informiert – ganz bequem per eMail.

Bildnachweise