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Evaluation of molecular targeted cancer drug by changes in tumor marker doubling times

  • Original Article—Liver, Pancreas, and Biliary Tract
  • Published:
Journal of Gastroenterology Aims and scope Submit manuscript

Abstract

Background

We evaluated the usefulness of tumor marker doubling time (DT) as an efficacy indicator of a molecular targeted anticancer agent.

Methods

Twenty-five patients with advanced hepatocellular carcinoma (HCC) received TSU-68, a multiple tyrosine kinase inhibitor. Exponential increase in HCC-specific tumor marker levels (alpha-fetoprotein or des-gamma-carboxyprothrombin) was seen in 15 of them prior to TSU-68 administration. The relationship between tumor marker DT and tumor volume DT was evaluated. Next, tumor marker DT in the first 8 weeks of TSU-68 administration was compared with tumor marker DT before treatment. Efficacy evaluation based on changes in tumor marker DT was compared with Response Evaluation Criteria In Solid Tumors (RECIST).

Results

Tumor marker DT and tumor volume DT were almost identical (r 2 = 0.94, P < 0.001) in each patient before TSU-68 administration. Efficacy evaluation based on changes in tumor marker DT on TSU-68 administration was in accordance with RECIST in 12/15 cases. Discordance was observed in three cases, for which RECIST indicated disease progression in spite of elongated tumor marker DT. Those cases showed substantial tumor necrosis without volume shrinkage or appearance of new lesions in spite of apparent effects on target lesions.

Conclusions

Serum tumor marker DT can be used to evaluate viable tumor burden irrespective of the presence of tumor necrosis which can compromise radiographic evaluation. This approach may be applicable to the evaluation of responses to chemotherapy, particularly to cytostatic agents (ClinicalTrials.gov number, NCT00784290).

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Abbreviations

AFP:

Alpha-fetoprotein

CEA:

Carcinoembryonic antigen

CR:

Complete response

CT:

Computed tomography

DCP:

Des-gamma-carboxyprothrombin

DT:

Doubling time

FGFR:

Fibroblast growth factor receptor

HCC:

Hepatocellular carcinoma

PD:

Progressive disease

PDGFR:

Platelet-derived growth factor receptor

PR:

Partial response

PSA:

Prostate-specific antigen

RECIST:

Response Evaluation Criteria In Solid Tumors

SD:

Stable disease

TACE:

Transcatheter arterial chemoembolization

VEGFR-2:

Vascular endothelial growth factor receptor-2

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Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan

    Kenichiro Enooku, Ryosuke Tateishi, Fumihiko Kanai, Yuji Kondo, Ryota Masuzaki, Tadashi Goto, Shuichiro Shiina, Haruhiko Yoshida, Masao Omata & Kazuhiko Koike

  2. Department of Gastroenterology, Chiba University Hospital, Chiba, Japan

    Fumihiko Kanai

  3. Yamanashi Prefectural Central Hospital, Kofu, Japan

    Masao Omata

Authors
  1. Kenichiro Enooku
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  2. Ryosuke Tateishi
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  3. Fumihiko Kanai
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  4. Yuji Kondo
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  5. Ryota Masuzaki
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  6. Tadashi Goto
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Correspondence to Ryosuke Tateishi.

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Enooku, K., Tateishi, R., Kanai, F. et al. Evaluation of molecular targeted cancer drug by changes in tumor marker doubling times. J Gastroenterol 47, 71–78 (2012). https://doi.org/10.1007/s00535-011-0462-2

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  • DOI: https://doi.org/10.1007/s00535-011-0462-2

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