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

Hidetoshi Hayashi, Takayasu Kurata, Yuichi Takiguchi, Makoto Arai, Koji Takeda, Kohei Akiyoshi, Koji Matsumoto, Takuma Onoe, Hirofumi Mukai, Nobuaki Matsubara, Hironobu Minami, Masanori Toyoda, Yusuke Onozawa, Akira Ono, Yoshihiko Fujita, Kazuko Sakai, Yasuhiro Koh, Ayano Takeuchi, Yasuo Ohashi, Kazuto Nishio & 1 others Kazuhiko Nakagawa

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)570-579
Number of pages10
JournalJournal of Clinical Oncology
Volume37
Issue number7
DOIs
Publication statusPublished - 2019 Jan 1

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Carboplatin
Gene Expression Profiling
Paclitaxel
Neoplasms
Therapeutics
Disease-Free Survival
Survival Rate
Drug Therapy
Survival
Microarray Analysis
Clinical Trials
Biopsy

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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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. / Hayashi, Hidetoshi; Kurata, Takayasu; Takiguchi, Yuichi; Arai, Makoto; Takeda, Koji; Akiyoshi, Kohei; Matsumoto, Koji; Onoe, Takuma; Mukai, Hirofumi; Matsubara, Nobuaki; Minami, Hironobu; Toyoda, Masanori; Onozawa, Yusuke; Ono, Akira; Fujita, Yoshihiko; Sakai, Kazuko; Koh, Yasuhiro; Takeuchi, Ayano; Ohashi, Yasuo; Nishio, Kazuto; Nakagawa, Kazuhiko.

In: Journal of Clinical Oncology, Vol. 37, No. 7, 01.01.2019, p. 570-579.

Research output: Contribution to journalArticle

Hayashi, H, Kurata, T, Takiguchi, Y, Arai, M, Takeda, K, Akiyoshi, K, Matsumoto, K, Onoe, T, Mukai, H, Matsubara, N, Minami, H, Toyoda, M, Onozawa, Y, Ono, A, Fujita, Y, Sakai, K, Koh, Y, Takeuchi, A, Ohashi, Y, Nishio, K & Nakagawa, K 2019, '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', Journal of Clinical Oncology, vol. 37, no. 7, pp. 570-579. https://doi.org/10.1200/JCO.18.00771
Hayashi, Hidetoshi ; Kurata, Takayasu ; Takiguchi, Yuichi ; Arai, Makoto ; Takeda, Koji ; Akiyoshi, Kohei ; Matsumoto, Koji ; Onoe, Takuma ; Mukai, Hirofumi ; Matsubara, Nobuaki ; Minami, Hironobu ; Toyoda, Masanori ; Onozawa, Yusuke ; Ono, Akira ; Fujita, Yoshihiko ; Sakai, Kazuko ; Koh, Yasuhiro ; Takeuchi, Ayano ; Ohashi, Yasuo ; Nishio, Kazuto ; Nakagawa, Kazuhiko. / 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. In: Journal of Clinical Oncology. 2019 ; Vol. 37, No. 7. pp. 570-579.
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abstract = "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.",
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T1 - 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

AU - Hayashi, Hidetoshi

AU - Kurata, Takayasu

AU - Takiguchi, Yuichi

AU - Arai, Makoto

AU - Takeda, Koji

AU - Akiyoshi, Kohei

AU - Matsumoto, Koji

AU - Onoe, Takuma

AU - Mukai, Hirofumi

AU - Matsubara, Nobuaki

AU - Minami, Hironobu

AU - Toyoda, Masanori

AU - Onozawa, Yusuke

AU - Ono, Akira

AU - Fujita, Yoshihiko

AU - Sakai, Kazuko

AU - Koh, Yasuhiro

AU - Takeuchi, Ayano

AU - Ohashi, Yasuo

AU - Nishio, Kazuto

AU - Nakagawa, Kazuhiko

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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.

AB - 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.

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