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01.04.2015 | Original Article

Parallel phase Ib studies of two schedules of buparlisib (BKM120) plus carboplatin and paclitaxel (q21 days or q28 days) for patients with advanced solid tumors

verfasst von: David M. Hyman, Alexandra E. Snyder, Richard D. Carvajal, John F. Gerecitano, Martin H. Voss, Alan L. Ho, Jason Konner, Jennifer L. Winkelmann, Megan A. Stasi, Kelsey R. Monson, Alexia Iasonos, David R. Spriggs, Philip Bialer, Mario E. Lacouture, Jerrold B. Teitcher, Nora Katabi, Matthew G. Fury

Erschienen in: Cancer Chemotherapy and Pharmacology | Ausgabe 4/2015

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Abstract

Purpose

Phosphatidylinositol-3-kinase I (PI3K) inhibition sensitizes a wide range of cancer cell lines to platinum/taxane-based chemotherapy. This phase I study combines buparlisib, a pan-class 1A PI3K inhibitor, with two schedules of carboplatin and paclitaxel for patients with advanced solid tumors (ClinicalTrials.gov, NCT01297452).

Methods

There were two regimens: Group 1 received carboplatin AUC 5 and paclitaxel 175 mg/m², on day 1 of a 21-day cycle with pegfilgrastim support; Group 2 received carboplatin AUC 5 (day 1) and paclitaxel 80 mg/m² (days 1, 8, and 15) on a 28-day cycle without growth factor support. In both groups, three dose levels of buparlisib were explored: 50, 80, and 100 mg/day. Primary endpoint was to identify recommended phase II doses of buparlisib in both groups.

Results

Thirty subjects enrolled, 16 in Group 1 and 14 in Group 2. The DLTs were elevated alkaline phosphatase (n = 1) and uncomplicated neutropenia (n = 2). The median numbers of cycles were 5 (Group 1) and 6 (Group 2). The MTDs for buparlisib were 100 mg/day in Group 1 and 80 mg/day in Group 2. Among 25 patients with measurable disease, the confirmed objective response rate was 20 % (one complete response, four partial responses). Among three patients with known loss of PTEN expression, all derived clinical benefit from treatment.

Conclusion

The addition of buparlisib to carboplatin + paclitaxel was well tolerated, and preliminary activity was notable against tumors with loss of PTEN expression.

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Titel: Parallel phase Ib studies of two schedules of buparlisib (BKM120) plus carboplatin and paclitaxel (q21 days or q28 days) for patients with advanced solid tumors
verfasst von: David M. Hyman
Alexandra E. Snyder
Richard D. Carvajal
John F. Gerecitano
Martin H. Voss
Alan L. Ho
Jason Konner
Jennifer L. Winkelmann
Megan A. Stasi
Kelsey R. Monson
Alexia Iasonos
David R. Spriggs
Philip Bialer
Mario E. Lacouture
Jerrold B. Teitcher
Nora Katabi
Matthew G. Fury
Publikationsdatum: 01.04.2015
Verlag: Springer Berlin Heidelberg
Erschienen in: Cancer Chemotherapy and Pharmacology / Ausgabe 4/2015
Print ISSN: 0344-5704
Elektronische ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-015-2693-z

Springer Medizin

Parallel phase Ib studies of two schedules of buparlisib (BKM120) plus carboplatin and paclitaxel (q21 days or q28 days) for patients with advanced solid tumors