ANTICANCER CHEMOSENSITIVITY AND GROWTH-RATE OF FRESHLY SEPARATED HUMAN COLORECTAL-CANCER CELLS ASSESSED BY IN-VITRO DNA-SYNTHESIS INHIBITION ASSAY

The present study was designed to assess the chemosensitivity profile of freshly separated colorectal cancer cells and to screen effective a gents for the design of new combination regimens. The DNA synthesis an d chemosensitivity (% inhibition of DNA synthesis by the anticancer ag ent) were successfully assessed in 184 samples (107 primary and 77 met astatic or recurrent lesions) from 152 patients with colorectal cancer using an H-3-thymidine incorporation assay, and the correlations betw een these two measures and various clinicopathological factors were an alysed. DNA synthesis was highest in nodal metastasis followed by mali gnant effusion, primary lesion, liver metastasis, and local recurrence . DNA synthesis liver metastasis and local recurrence were significant ly lower than in other lesions. The results of the chemosensitivity as say are as follows: 5-FU seems to be the most beneficial for primary c olorectal cancer; carboquone (CQ), etoposide (VP-16), 5-FU, and mitomy cin-C (MMC) for nodal metastasis; CQ cisplatin (CDDP), 5-FU, adriamyci n (ADR) and VP-16 for malignant effusion; and VP-16, CDDP and CQ for l iver metastasis. However, the present results showing the chemosensiti vity profiles in different lesions suggest that regimens including 5-F U with VP-16 and CQ in addition to MMC or ADR may be applicable for al l kinds of colorectal cancer lesions. These results demonstrated the h eterogeneity in the chemosensitivity of colorectal eancer, which sugge sts not only the necessity of patient-specific chemotherapy dependent on the sensitivity assay, bur also the usefulness of the present resul ts in the choice of agents for widely applicable combination regimens for colorectal cancer.