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For many years the standard chemotherapy for advanced colorectal carcinoma has been 5-FU and leucovorin. However, despite this combination therapy, patient prognosis is not good. Pharmacokinetic modulating chemotherapy (PMC) is a new therapeutic concept in combination with continuous 5-fluolouracil (5-FU) infusion and UFT. The PMC regimen that we have advocated has proved to be highly effective in treating colorectal carcinoma.
We reported that PMC improved the prognosis of rectal carcinoma with P53 overexpression after radical resection in 1988, and markedly improved the median survival period for unresectable colorectal carcinoma in 1999. In addition, hepatic arterial infusion PMC drastically decreased hepatic recurrence after curative resection of hepatic colorectal secondaries in 2000. Thus, PMC significantly improved the prognosis of advanced colorectal carcinoma and also indicated tolerable compliance and cost effectiveness.
In 2001, an in vitro study showed that the PMC regimen is based on targeting at least two different phase of the cell cycle. These two different pathways depend on the integrity of the schedule-oriented cell cycle check points ; G2-M-phase arrest and mitotic catastrophe at a lower dose of 5-FU , and G1-S-phase arrest and apoptosis at a higher dose of 5-FU. In this study, G2-M-phase arrest and mitotic catastrophe at a lower dose of 5-FU were induced via a P53-independent pathway. In conclusion, development of a modified PMC regimen in combination with chemotherapeutic agents that target different checkpoints may heighten the efficacy and broaden the selectivity of 5-FU.
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