Randomized Phase II Trial Comparing Site-Specific Treatment Based on Gene Expression Profiling With Carboplatin and Paclitaxel for Patients With Cancer of Unknown Primary Site

J Clin Oncol. 2019 Mar 1;37(7):570-579. doi: 10.1200/JCO.18.00771. Epub 2019 Jan 17.


Purpose: Although gene expression profiling is a promising diagnostic technique to determine the tissue of origin for patients with cancer of unknown primary site (CUP), no clinical trial has evaluated yet site-specific therapy directed by this approach compared with empirical chemotherapy. We therefore performed a randomized study to assess whether such site-specific therapy improves outcome compared with empirical chemotherapy in previously untreated patients with CUP.

Patients and methods: Comprehensive gene expression profiling was performed by microarray analysis, and an established algorithm was applied to predict tumor origin. Patients with CUP were randomly assigned (1:1) to receive standard site-specific therapy or empirical paclitaxel and carboplatin (PC). The primary end point was 1-year survival rate.

Results: One hundred thirty patients were randomly assigned and had sufficient biopsy tissue for molecular analysis. Efficacy analysis was performed for 50 and 51 patients in the site-specific therapy and empirical PC arms, respectively. Cancer types most commonly predicted were pancreatic (21%), gastric (21%), and lymphoma (20%). The 1-year survival rate was 44.0% and 54.9% for site-specific treatment and empirical PC ( P = .264), respectively. Median overall and progression-free survival were 9.8 and 5.1 months, respectively, for site-specific treatment versus 12.5 and 4.8 months for empirical PC ( P = .896 and .550, respectively). Median overall survival (16.7 v 10.6 months; P = .116) and progression-free survival (5.5 v 3.9 months; P = .018) were better for predicted more-responsive than less-responsive tumor types.

Conclusion: Site-specific treatment that was based on microarray profiling did not result in a significant improvement in 1-year survival compared with empirical PC, although prediction of the original site seemed to be of prognostic value.

Publication types

  • Clinical Trial, Phase II
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Biomarkers, Tumor / genetics*
  • Carboplatin / adverse effects
  • Carboplatin / therapeutic use*
  • Female
  • Gene Expression Profiling*
  • Genetic Predisposition to Disease
  • Humans
  • Japan
  • Male
  • Middle Aged
  • Neoplasms, Unknown Primary / drug therapy*
  • Neoplasms, Unknown Primary / genetics
  • Neoplasms, Unknown Primary / pathology
  • Paclitaxel / adverse effects
  • Paclitaxel / therapeutic use*
  • Patient Selection
  • Phenotype
  • Precision Medicine / methods*
  • Predictive Value of Tests
  • Progression-Free Survival
  • Prospective Studies
  • Time Factors
  • Transcriptome*


  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Carboplatin
  • Paclitaxel

Associated data

  • UMIN-CTR/UMIN000001919