Paclitaxel/carboplatin with or without belinostat as empiric first‐line treatment for patients with carcinoma of unknown primary site: A randomized, phase 2 trial. Issue 10 (21st January 2015)

• Record Type: Journal Article
• Authors: Hainsworth, John D.; Daugaard, Gedske; Lesimple, Thierry; Hübner, Gerdt; Greco, F. Anthony; Stahl, Michael J.; Büschenfelde, Christian Meyer Zum; Allouache, Djelila; Penel, Nicolas; Knoblauch, Poul; Fizazi, Karim S.
• Is Part Of: Cancer. Volume 121:Issue 10(2015)
• Page Start: 1654
• Page End: 1661
• Publication Date: 2015-01-21
• Subjects: Cancer -- Periodicals; Cancer -- Cytopathology -- Periodicals; 616.99405
• DOI: 10.1002/cncr.29229
• Languages: English
• ISSNs: 0008-543X

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="cncr29229-sec-0001" sec-type="section"> <title>BACKGROUND</title> <p>The objective of this study was to evaluate the efficacy of belinostat, a histone deacetylase inhibitor, when added to paclitaxel/carboplatin in the empiric first‐line treatment of patients with carcinoma of unknown primary site (CUP).</p> </sec> <sec id="cncr29229-sec-0002" sec-type="section"> <title>METHODS</title> <p>In this randomized phase 2 trial, previously untreated patients with CUP were randomized to receive belinostat plus paclitaxel/carboplatin (group A) or paclitaxel/carboplatin alone (group B) repeated every 21 days. Patients were re‐evaluated every 2 cycles, and those without disease progression continued treatment for 6 cycles. Patients in group A then continued receiving single‐agent belinostat, whereas patients in group B stopped treatment. The primary endpoint was progression‐free survival (PFS): The authors postulated that the addition of belinostat would improve PFS from 5 months (expected with paclitaxel/carboplatin) to 8 months.</p> </sec> <sec id="cncr29229-sec-0003" sec-type="section"> <title>RESULTS</title> <p>In total, 89 patients were randomized (group A, n = 44; group B, n = 45), and the demographics and disease characteristics were balanced between the 2 groups. The addition of belinostat to paclitaxel/carboplatin did not improve PFS (group A, 5.4 months [95% confidence interval, 3.0‐6.0 months]; group B, 5.3 months [95% confidence interval, 2.8‐6.6 months]; <italic>P</italic> = .85). Overall survival was 12.4 months for group A versus 9.1 months for group B (<italic>P</italic> = .20). The response rate favored the belinostat group (45% vs 21%; <italic>P</italic> = .02). Belinostat resulted in a modest increase in treatment toxicity.</p> </sec> <sec id="cncr29229-sec-0004" sec-type="section"> <title>CONCLUSIONS</title> <p>The addition of belinostat to paclitaxel/carboplatin did not improve the PFS of patients with CUP who were receiving first‐line therapy, although the patients who received belinostat had a higher investigator‐assessed response rate. Future trials in CUP should focus on specific subsets, defined either by the predicted tissue of origin or by the identification of targetable molecular abnormalities. <bold><italic>Cancer</italic> 2015;121:1654–1661</bold>. © <italic>2015 American Cancer Society</italic>.</p> </sec> </abstract>