Page 168 - Fluorescence-guided cancer surgery

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Chapter 10
Pharmacokinetics
The maximum blood plasma concentration was achieved with each dose immediately at the end of the infusion and declined thereafter with a half- life of 2-3 hours (Figure S4, online available). Table S2 summarizes the most important pharmacokinetics (PK) parameters in each treatment group (online available) OTL38 excreted in the urine (expressed as a percentage of the dose administered) increased with increasing dose, and the highest level was approximately 11% for the highest dose (0.2 mg/kg). It is therefore reasonable to assume that the relatively low recovery is due in part to the lower limit of detection for OTL38 in urine.
Pharmacokinetics in super cial tissue
Figure 1 shows example images obtained using the Artemis imaging system. Although OTL38 was cleared from the plasma 2-3 hours after intravenous infusion, our analysis of the uorescence signal in the skin revealed that uorescence increased initially, remained increased for six hours, and then decreased with a half-life of approximately 15 hours (Figure 1).
Clinical trial in patients with ovarian cancer
Fourteen patients initially enrolled in this study. However, because the study drug was temporary unavailable, one patient could not participate, another patient withdrew from the study. Thus, a total of 12 patients, 49 to 77 years of age with a BMI of 20-41 kg/m2 received OTL38 (see Figure S5 for the CONSORT ow diagram, online available). The surgical procedure, histology, di erentiation grade, and International Federation of Gynecology and Obstetrics (FIGO) stages are summarized in Table 1.
Dose escalation
Patients 1, 2, and 3 received a starting dose of 0.025 mg/kg. After we reviewed the safety and e cacy data, the dose was increased to 0.05 mg/kg in the next three patients. However, when the 3 patients 4, 5, and 6 received this higher dose, the number and severity of symptoms (primarily consisting of abdominal discomfort, nausea, and pruritus) increased. In addition, TBR appeared to decrease. Therefore, the dose was decreased to 0.0125 mg/kg for the next three patients (patients 7, 8, and 9), yielding fewer, less severe symptoms, as well as an increase in TBR. Nevertheless, even at this lowest dose, mild, self-limiting