Use of therapeutic drug monitoring of cancer chemotherapy to modify initial per-protocol doses.

Abstract

e13015 Background: Therapeutic drug monitoring (TDM) is not routinely used for chemotherapy agents. Nonetheless, TDM has the potential to improve the clinical benefit of chemotherapy agents due to their narrow therapeutic index and highly variable pharmacokinetics. The main objective of this study was to evaluate the dose modifications on the standard dosing regimen based on the individual pharmacokinetic (PK) parameters of six antineoplasic drugs (oxaliplatin, cisplatin, doxorubicin, irinotecan, paclitaxel, and 5-fluorouracil). Methods: A total of 187 patients (pts) (764 cycles), treated with either drug tested, were monitored and doses in second or subsequent cycles were pharmacokinetically adjusted until the patients reached the target plasma concentration. Bayesian estimates of individual PK parameters were calculated using a population PK model previously published and were used for pharmacokinetic-based dose adaptation. Patient's toxicities were assessed before each cycle using the National Cancer Institute Common Toxicity Criteria. Results: The main results are shown in the Table. In one out of four patients, the dose was increased an average of 12% without increasing the toxicity. In one out of four patients, the dose was decreased an average 16% due to toxicity caused by the complexity of the therapeutic program but not due to previous dose increases. These results evidence TDM might benefit one out of two oncology patients. Conclusions: Half of the patients evaluated did not achieve the target plasma concentration during the first cycle of chemotherapy. TDM of anticancer drugs is a tool to optimize cancer treatment and ensure that patients receive the right dose. Drug N (pts/cycles) Dose maintenance(% pts) Dose increase (% pts) Dose decrease (% pts) Avg dose increase (%) Avg dose decrease (%) Oxaliplatin 13/51 77 — 23 — 22 Cisplatin 17/62 35 47 18 14 15 Doxorubicin 21/67 52 19 29 13 13 Irinotecan 39/165 31 46 23 13 18 Paclitaxel 46/182 61 4 35 10 12 5-fluorouracil 51/237 37 51 12 12 15 Total 187/764 49 28 23 12 16 No significant financial relationships to disclose.