Insulin-Enhanced Antitumor Effect of 5-Fluorouracil in vivo

OBJECTIVE To determine if insulin treatment can enhance the antitumor effect of 5-fluorouracil(5-FU),and to explore the mech- anism of the enhancement of insulin. METHODS S180 sarcoma,H22 liver cancer and human Eca-109 esophageal cancer cells were transplanted into nude mice to evaluate the inhibitory effect on tumor growth of insulin alone or in combination with 5-FU.The levels of serum insulin-like growth factor-I(IGF-I)and insulin-like growth factor binding protein-3 (IGFBP-3)were determined. RESULTS Compared with 5-FU treatment alone,the tumor weight of H22 liver cancer and S180 sarcoma was reduced further with high,medium and low-dose insulin(0.09,0.06,0.03 U/20 g) +5-FU treatment.When a high dosage of insulin+5-FU was ad- ministered,tumor weight was significantly reduced(P<0.05).The inhibitory rate of growth of S180 sarcoma and H22 liver cancer reached 50.2% and 51.4%,respectively,which was significantly higher than 24.9% and 27.9% in the group receiving 5-FU alone (P<0.05).High,medium and low-dose insulin combined with 5-FU significantly inhibited the growth of Eca-109 cancer cells (P<0.05).Compared with the control group,the level of serum IGF-1 decreased(P<0.05),whereas the level of serum IGFBP-3 slightly increased in the 5-FU±insulin groups(P>0.05).In mice with H22 liver cancer and S180 sarcoma the IGF-1 level with high- dose insulin+5-FU treatment was significantly lower compared to treatment with 5-FU alone(P<0.05),but the difference was not significant in mice transplanted with esophageal cancer cells. CONCLUSION Insulin can enhance the anti-tumor effect of 5-FU without significantly increasing 5-FU toxicity.Although changes in the serum IGF-1 or IGFBP-3 level do not explain the mechanism of the insulin-induced enhancement on 5-FU on growth,a decrease in the level of serum IGF-1 and an increase in serum IGFBP-3 may be important in the chemotherapeutic response.

Oxaliplatin combined with 5-fluorouracil, leucovorin regimen for patients with advanced colorectal cancer

Objective: To observe the efficacy and tolerability of continuously infusing 5-fluorouracil (5-FU) / folic acid com- bined with oxaliplatin (L-OHP/5-FU/LV regimen) as first line treatment in advanced colorectal cancer. Methods: 23 patients of advanced colorectal cancer were treated with 5-FU 500 mg/d, civ, d1–d5, d8–d12, leucovorin 100 mg/d, iv gtt, d1, d8, folic acid tablet 60 mg/d, po, d2–d5, d9–d12, and oxaliplatin 65 mg/(m2?d), iv gtt, d1, d8, repeated every 21 days (one cycle).The effect was evaluated after two cycles. Results: Complete response in 2 cases and partial response in 10 cases were observed with an overall response rate of 47.18%. Adverse effects were mainly grade 1–2, including nausea, vomiting, diarrhea, dental ulcer, peripheral neuritis and myelosuppression. Conclusion: L-OHP/5-FU/LV regimen is an effective and better tolerated alterna- tive treatment in advanced colorectal cancer and yields promising clinical application.