[Effects of irinotecan and 5-FU combination therapy in gastric cancer--is combination therapy synergic?]

Gan To Kagaku Ryoho. 2010 Nov;37(11):2125-9.
[Article in Japanese]

Abstract

The response rate of Irinotecan for gastric cancer is reported to be 18. 4%. The rate is improved by combination with 5-FU. However, it remains unclear whether or not the effect of the two drugs is synergy or antagonistic. The purpose of this study is to clarify whether the effect of Irinotecan and 5-FU in gastric cancer is synergy or antagonistic. We performed study using 13 specimens removed surgically and 2 specimen collected from ascites. We performed the Collagen Gel Droplet Embedded Culture Drug Sensitivity Test (CD-DST) with 3 assumptions. In the first assumption, we let 5-FU come in contact with a tumor at a level of 1 mg/mL for 24 hours. The second assumption was SN-38 at a level of 30 mg/mL for 24 hours and the 3rd assumption was SN-38 at a level of 30 mg/mL and 5-FU at a level of 1 mg/mL for 24 hours. If the combination index was more than 1, the combination therapy was judged as synergic; if less than 1, it was considered antagonistic.

Results: The inhibition rate of combination therapy was significantly higher than that of monotherapy. The inhibition rate of combination therapy was significantly correlate with that of monotherapy (Irinotecan; r=0.704, p=0.003, 5-FU; r=0.746, p=0.001). The combination index was antagonistic in only 6 of 15 cases. However, it was synergic in all well-differentiated adenocarcinomas (4/4).

Discussion: We conclude that combination therapy is antagonistic in most cases of gastric cancer in vitro. However, it may be synergic in well-differentiated adenocarcinomas.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antimetabolites, Antineoplastic / administration & dosage
  • Antineoplastic Agents, Phytogenic / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Camptothecin / administration & dosage
  • Camptothecin / analogs & derivatives
  • Drug Antagonism
  • Drug Synergism
  • Female
  • Fluorouracil / administration & dosage
  • Humans
  • In Vitro Techniques
  • Irinotecan
  • Male
  • Middle Aged
  • Stomach Neoplasms / drug therapy*

Substances

  • Antimetabolites, Antineoplastic
  • Antineoplastic Agents, Phytogenic
  • Irinotecan
  • Fluorouracil
  • Camptothecin