Recommendation of dose banding of cytotoxics according to pharmacokinetic criteria.

Abstract

2549 Background: Dose-banding has been recently suggested in order to optimize chemotherapy preparation. Ranges (or bands) of body surface area (BSA) are predefined. The individual dose of a particular patient is calculated according to a single BSA value per band, usually the mid-point of the BSA band in which the actual BSA of the patient lies. Thanks to this simple procedure, chemotherapy provision can be rationalized and chemotherapies can be prepared in advance for drugs with sufficient long-term drug stability. The primary purpose of dose-banding is to reduce patient waiting time and improve capacity planning of the pharmacy production, but additional benefits can also be found, such as reduced potential for medication errors, reduced drug wastage, and prospective quality control of preparations. The objective of this analysis was to compare dose-banding to individual BSA-dosing (current practice) according to pharmacokinetic (PK) criteria. Methods: Dose-banding was defined according to three bands of BSA: BSA<1.7m², 1.7m²≤BSA<1.9m², and BSA≥1.9m² for which the values of 1.55m², 1.80m², and 2.05m² were allocated, respectively. By using individual actual values of clearance of six drugs (cisplatin, docetaxel, paclitaxel, doxorubicin, topotecan, and irinotecan) from a total of 1,206 adult cancer patients, the AUCs corresponding to the two dosing methods were compared to a target value of AUC for each drug. Results: Over all 6 drugs, by using dose-banding the percent change of individual dose in comparison with BSA dosing ranged between -14% and +22%. In terms of capacity to attain the target AUC, there was no significant difference in precision when using dose-banding as compared to BSA-dosing for all drugs except paclitaxel (precision of 23.2% versus 21.8%, respectively). For all drugs including paclitaxel, distributions of AUC values were very similar with both dosing methods. Conclusions: For these 6 drugs and maybe others, dose-banding may be implemented without any risk of increasing interindividual plasma exposure. Dose-banding would make it possible to anticipate chemotherapy preparation and analytical control without any delay for the patients.