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A set of 5 time-points from zero to 10 h in the 6th dose cycle was available for two of the four patients while for the other two patients only two time-points were available each, for one patient in the 7th dose-cycle and for the other patient in the 8th dose-cycle.
The two patients with only two samples per dose cycle were exposed to 1747 and 2156 ng h/mL for periods of 2.3 and 6.5 h, respectively.
The current conceptual model proposes that each anthracycline dose (cycle) induces an amount of damage to the myocardium.
In the immediate treatment arm, all patients began in state >6/12 with a 3-month loading dose cycle.
Increasing the dose to 500 mg sustained anti IL-6Rα over the dose cycle in anti IL-6Rαmilar tovertheIL-6, resulting in higher efficacy.
PK parameters (overall and by histology) following a single dose (cycle 1 day 1), and mean Ctrough values after multiple doses for dose‐compliant patients (Supporting Table 3) were consistent with those previously reported.
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In addition, blood samples for determination of trough levels of sunitinib and SU12662 were taken for Schedule 4/2 pre-dose on day 1 (cycles 1 3) and 24 h after the last dose (cycles 1 3 and 5), and for Schedule 2/1 were obtained before dosing on day 1 (cycles 1, 4, and 6), days 8 and 15 (cycle 1) and day 14 (cycles 4, 6, and 10).
Peripheral blood progenitor cells were harvested by leukapheresis after treatment with cyclophosphamide and filgrastim and re-infused after the high-dose cycle.
Serum samples were collected before and after ficlatuzumab dosing at screen or pre-dose cycle 1 day 1 (C1D1), pre-dose C3D1 and subsequent odd cycles, as well as at 1-month follow-up.
Of the 18 patients who were assessed for toxicities, 5 (27.8%) received at least one fully dosed cycle, 2 (11.1%) of whom received fully dosed cycles for all cycles administered.
No change was observed from first to second dosing cycle (Fig. 2b).
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