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 Journal Article
| Authors: | Hyman, D. M.; Snyder, A. E.; Carvajal, R. D.; Gerecitano, J. F.; Voss, M. H.; Ho, A. L.; Konner, J.; Winkelmann, J. L.; Stasi, M. A.; Monson, K. R.; Iasonos, A.; Spriggs, D. R.; Bialer, P.; Lacouture, M. E.; Teitcher, J. B.; Katabi, N.; Fury, M. G. |
| Article Title: | 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 |
| 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. © 2015 Springer-Verlag Berlin Heidelberg. |
| Keywords: | paclitaxel; carboplatin; pten; buparlisib; phase ib |
| Journal Title: | Cancer Chemotherapy and Pharmacology |
| Volume: | 75 |
| Issue: | 4 |
| ISSN: | 0344-5704 |
| Publisher: | Springer |
| Date Published: | 2015-04-01 |
| Start Page: | 747 |
| End Page: | 755 |
| Language: | English |
| DOI: | 10.1007/s00280-015-2693-z |
| PROVIDER: | scopus |
| PUBMED: | 25672916 |
| PMCID: | PMC6698915 |
| DOI/URL: | |
| Notes: | Export Date: 4 May 2015 -- Source: Scopus |
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