Tailored dose chemotherapy and the relationship with PK.

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We developed and established a new dose-finding system, the individualized maximum repeatable dose (iMRD), suitable to induce prolonged TTP rather than tumor shrinkage, which is determined by toxicity grade 1 marrow depression. We applied this system in weekly paclitaxel therapy for・21 metastatic gastric cancer patients as second line. We determined the iMRD at the 5th week, after weekly dose adjustments. We started at 60 mg/m^2 of paclitaxel and repeated the treatment with an increase or a decrease of 10 mg/m^2 each week, if toxicity was 0 or more than grade 1, respectively. Moreover, we studied the correlation between iMRD and AUC at 60 mg/m2 of paclitaxel in 11 patients. The iMRD of weekly gemcitabine was 40 mg/m^2 in 1 patient, 50 mg/m^2 in 6 patients, 60 mg/m^2 in 6 patients, 70 mg/m^2 in 4 patients, and 80 mg/m^2 in 1 patient, demonstrating significant differences among individual patients. Grade 3 marrow depression occurred in 2 patients (9.5%). Of these 21 patients, 5 (23.8%), 12 (57.2%) and 4 (19.0%) patients showed PR, SD and PD, respectively. The median of TTP and survival was 5.0 months and 9.5 months, respectively. Means of AUC of the patients whose iMRD were less than 50 mg/m^2 (n=3), 50 mg/m^2 or 60 mg/m^2(n=4), more than 60 mg/m^2(n=3) were 4133, 3721, and 2057 ng/ml*hr, respectively. There were reverse correlation between iMRD and AUC. These results suggest that iMRD is a simple method to determine an individual's tailored dose for chemotherapy and could be the optimal dose for patients with non-curable cancers such as metastatic stomach cancer, and could be predicted by AUC of the starting dose.