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

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).

• Authors: Kenichiro Enooku, Ryosuke Tateishi, Fumihiko Kanai, Yuji Kondo, Ryota Masuzaki, Tadashi Goto, Shuichiro Shiina, Haruhiko Yoshida, Masao Omata, Kazuhiko Koike
• Journal: Journal of gastroenterology (J Gastroenterol) Vol. 47 Issue 1 Pg. 71-8 (Jan 2012) ISSN: 1435-5922 [Electronic] Japan
• PMID: 21935635 (Publication Type: Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article, Multicenter Study)

Chemical References

• Antineoplastic Agents
• Biomarkers
• Biomarkers, Tumor
• Indoles
• Oxindoles
• Propionates
• Protein Kinase Inhibitors
• Protein Precursors
• Pyrroles
• alpha-Fetoproteins
• acarboxyprothrombin
• Prothrombin
• orantinib

Topics

• Aged
• Antineoplastic Agents (pharmacology, therapeutic use)
• Biomarkers (blood)
• Biomarkers, Tumor (blood)
• Carcinoma, Hepatocellular (drug therapy, pathology)
• Disease Progression
• Female
• Humans
• Indoles (pharmacology, therapeutic use)
• Liver Neoplasms (drug therapy, pathology)
• Male
• Middle Aged
• Molecular Targeted Therapy (methods)
• Oxindoles
• Propionates (pharmacology, therapeutic use)
• Protein Kinase Inhibitors (pharmacology, therapeutic use)
• Protein Precursors (blood)
• Prothrombin
• Pyrroles
• Time Factors
• Treatment Outcome
• Tumor Burden (drug effects)
• alpha-Fetoproteins (metabolism)