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. Cancer 2015;121:1654–1661. © 2015 American Cancer Society.

“Metastatic Cancer of Unknown Primary” or “Primary Metastatic Cancer”?

“…The vast majority of these regimens, which frequently contain taxanes, gemcitabine and irinotecan, are based on results from single-arm, phase II data to support their use in CUP at best (23)(24)(25). Additionally, data from randomized studies are scarce and mostly come from small trials providing suggestions rather than clear guidance regarding preferred regimens (26)(27)(28). For example, the superiority of polychemotherapy compared to single agent chemotherapy is an open issue in CUP.…”

“…In the enrolled population of about 50 patients, no clear PFS advantage emerged from comparing cisplatin and gemcitabine vs. cisplatin alone. Regarding biologically targeted therapies, a single randomized trial evaluated the addition of the histone deacetylase inhibitor belinostat to paclitaxel and carboplatin (28). In this small, phase II randomized trial, belinostat did not prolong PFS, which was the primary study endpoint, but was associated with increased response rate.…”

Precision medicine based on epigenomics: the paradigm of carcinoma of unknown primary

“…28 The other 80-85% of CUP cases have a very poor response to treatment, and without any suspicion of its primary tumor, its treatment involves an empirical schedule consisting of either taxanes or platins or a combination of the two, in conjunction with gemcitabine. 29 The median survival of this group is a disheartening 6-9 months, response rates are around 20%, and the 1-year survival rate barely reaches 25%. 30 Nevertheless, within this non-specific subset of patients, two prognostic groups can be identified on the basis of their performance status and lactate dehydrogenase (LDH) serum levels.…”

Gallbladder Cancer Showing a Great Response to Paclitaxel Plus Carboplatin Chemotherapy: A Case Report

“…In Japan, paclitaxel plus carboplatin therapy has become the standard treatment for unknown primary cancer. 7 Paclitaxel, classified as an antimicrotubule agent, is a novel chemotherapeutic agent that works by stopping the cancer cells from dividing, thereby blocking the growth of cancer. Paclitaxel has already been used extensively as one of the key drugs for the treatment of ovarian, breast, and gastric cancers.…”