Future prospects of personalized chemotherapy in gastric cancer patients: results of a prospective randomized pilot study.
In the present study, in order to evaluate the feasibility of personalized chemotherapy, a prospective randomized pilot study was performed in 30 advanced or recurrent gastric cancer patients. As we have demonstrated previously, the expressions of mRNA from tumor biopsy samples for seven molecular markers, i.e., dihydropyrimidine dehydrogenase (DPD), glutathione S-transferase (GST)-pi, beta-tubulin (tub), O6-methylguanine-DNA methyltransferase (MGMT), multiple drug-resistant protein (MRP)-1, NADPH/quinone oxidoreductase (NQO)-1, and cytochrome p450 (P450), were examined by reverse transcription-polymerase chain reaction (RT-PCR) analysis and therapy was recommended in a flow chart that depended on the level of expression of these predictive molecular markers. We chose 12 therapeutic plans, including best supportive care (BSC). We treated 15 patients according to the gene expression profiles, and the remaining 15 patients (controls) were treated without recommended regimens, and the therapy was continued after the expression profiles were checked. Interestingly, 11 of 26 lesions (42.3%) responded after treatment given according to gene expression analysis; however, no clinical response was detected in the control group. The prediction of the response, including resistance, was successful in 75.9% by the gene expression profiles. Moreover, the survival of the patients with the recommended treatment was better than that of patients without a recommended protocol. These results indicate that personalized treatment may be beneficial for gastric cancer chemotherapy and further randomized trials should be carried out in the future.
Yoshida
Kazuhiro
K
Department of Surgical Oncology, Research Institute for Radiation Biology and Medicine, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan.
Tanabe
Kazuaki
K
Ueno
Hideaki
H
Ohta
Kouji
K
Hihara
Jun
J
Toge
Tetsuya
T
Nishiyama
Masahiko
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D002945:Cisplatin / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004342:Drug Hypersensitivity / Q000209:etiology / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D004358:Drug Therapy / Q000639:trends*; D005260:Female; D015870:Gene Expression / Q000235:genetics; D020869:Gene Expression Profiling; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000235:genetics / Q000401:mortality; D010094:Oxonic Acid / Q000008:administration & dosage; D010865:Pilot Projects; D011237:Predictive Value of Tests; D011446:Prospective Studies; D011725:Pyridines / Q000008:administration & dosage; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D016019:Survival Analysis; D005641:Tegafur / Q000008:administration & dosage; D016896:Treatment Outcome
D000964:Antimetabolites, Antineoplastic; D004338:Drug Combinations; D011725:Pyridines; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D002945:Cisplatin