Dose scheduling and pharmacokinetic (PK) study of trastuzumab in patients (pts) with HER2/neu overexpressing breast cancer?

Abstract

1109 Has been demonstrated that 10–20 μg/mL is the minimum serum trough concentration (Cmin) of trastuzumab that causes maximal tumor growth inhibition. This concentration was shown to be achievable using a weekly (4 mg/kg loading dose followed by 2 mg/kg weekly) and a three-weekly (8 mg/kg loading dose followed by 6 mg/kg) schedule, but only indirect comparisons of the two schedule have been performed. We prospectively analysed the PK distribution of trastuzumab in three different schedules, as follows: weekly (cohort I), bi-weekly (trastuzumab 6 mg/kg loading dose followed by 4 mg/kg, cohort II) and three-weekly schedule (cohort III). The PK analysis was performed in 18 pts (4 pts receiving the loading dose of cohort III, 8 pts receiving the maintenance dose of cohort III, 3 pts receiving the maintenance dose of cohort II, and 3 pts receiving loading dose of cohort I). Of the 18 pts analyzed, 9 were metastatic. The median age was 54 years (range 39–76), the median weight was 61,5 kg (range 53–80). At diagnoses, 10 pts had stage I disease, 5 and 3 pts had stage II and III respectively, ER was negative in 10 pts and PgR was negative in 12 pts; Ki67 was highly expressed in 14 pts; Her/neu was overexpressed and amplified in 16 and 2 pts respectively. To evaluate preliminary interpatient variability, 3 pts receiving 6mg/kg of trastuzumab repeated the PK analysis after four cycles: the comparison between two groups was not statistically significative. Comparison of Cmax and AUC mean between groups was statistically significative (P<0.05, Bonferroni test) except for 8 mg/kg vs 6 mg/kg AUC.All the doses and schedules analysed are able to reach the minimum serum concentration of trastuzumab that causes the maximal tumor growth inhibition. [Table: see text] No significant financial relationships to disclose.

External validity of clinical trials with diverse trastuzumab-based chemotherapy regimens in advanced gastroesophageal adenocarcinoma: data from the AGAMENON-SEOM registry

“…10,13 Tratuzumab dosing in bi-weekly schedules is different, albeit there are data that suggest that these dosages are capable of reaching the minimum concentrations associated with inhibition of tumor growth. 31 One possible cause for this advantage in the AGAMENON registry is that by using ToGA or CAPOX-T regimens, there was a tendency to assume that the treatment had a pre-defined duration as considered for the CF or XP regimens, while with FOLFOX-T, FU may have been managed differently, which facilitated maintenance together with trastuzumab. Optimal treatment duration has not been well defined in advanced gastric cancer.…”

Trastuzumab therapy in breast cancer: To reload or not to reload?

“…For example, the study by Carter et al 16 seemed to plateau at 8-10 mg/mL, while Tokuda et al 13 suggested plateauing at 0.1-1.0 mg/mL from their data. However, subsequent clinical trials generally aimed for serum levels of >10-20 mg/mL 9,10,[12][13][14][15] and none was designed to achieve >50 mg/mL. A steady state of serum level is reached for the weekly and three-weekly dosing after 20 and 12 weeks, respectively.…”