Paclitaxel/carboplatin with or without belinostat as empiric first-line treatment for patients with carcinoma of unknown primary site: A randomized, phase 2 trial.

Abstract

BACKGROUND:

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).

METHODS:

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.

RESULTS:

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]; P = .85). Overall survival was 12.4 months for group A versus 9.1 months for group B (P = .20). The response rate favored the belinostat group (45% vs 21%; P = .02). Belinostat resulted in a modest increase in treatment toxicity.

CONCLUSIONS:

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.

• Authors: John D Hainsworth, Gedske Daugaard, Thierry Lesimple, Gerdt Hübner, F Anthony Greco, Michael J Stahl, Christian Meyer Zum Büschenfelde, Djelila Allouache, Nicolas Penel, Poul Knoblauch, Karim S Fizazi
• Journal: Cancer (Cancer) Vol. 121 Issue 10 Pg. 1654-61 (May 15 2015) ISSN: 1097-0142 [Electronic] United States
• PMID: 25611313 (Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 American Cancer Society.

Chemical References

• Histone Deacetylase Inhibitors
• Hydroxamic Acids
• Sulfonamides
• Carboplatin
• belinostat
• Paclitaxel

Topics

• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Carboplatin (administration & dosage, adverse effects)
• Carcinoma (drug therapy)
• Disease-Free Survival
• Drug Administration Schedule
• Female
• Histone Deacetylase Inhibitors (administration & dosage, adverse effects)
• Humans
• Hydroxamic Acids (administration & dosage, adverse effects)
• Kaplan-Meier Estimate
• Male
• Middle Aged
• Neoplasms, Unknown Primary (drug therapy)
• Paclitaxel (administration & dosage, adverse effects)
• Sulfonamides (administration & dosage, adverse effects)
• Treatment Failure