Abstract | BACKGROUND: PATIENTS AND METHODS: Two open-label, multicenter phase I studies evaluated weekly (3-15 mg/kg) or every-2-weeks (6-15 mg/kg) dosing of cixutumumab in patients with advanced solid tumors. Serial blood samples for PK were collected up to 168-336 h (day 8-15) following the first administration of cixutumumab. Efficacy was evaluated as best overall tumor response. RESULTS: A total of 24 and 16 patients were enrolled in the weekly and every-2-week dosing studies, respectively. Treatment-emergent adverse events (≥10%) included hyperglycemia, fatigue, anemia, nausea, and vomiting. Severe adverse events (AE) were infrequent; one serious AE (grade 3 electrocardiogram QT prolongation) was deemed possibly cixutumumab-related (10 mg/kg every-2-weeks). One death occurred due to disease progression (6 mg/kg weekly cohort). Maximum serum concentrations increased with dose. A maximum tolerated dose was not identified; pre-determined target serum minimum concentrations (60 μg/mL) were achieved with ≥6 mg/kg weekly and ≥10 mg/kg every-2-week dosing. Cixutumumab terminal elimination half-life is approximately a week (individual range, t1/2 = 4.58-9.33 days based upon 10 mg/kg every 2 weeks). Overall, stable disease was achieved in 25% of all patients. CONCLUSIONS:
Cixutumumab was associated with favorable safety and PK profiles. A dosing regimen of 10 mg/kg every 2 weeks was recommended for subsequent disease-focused clinical trials.
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Authors | C S Higano, J Berlin, M Gordon, P LoRusso, S Tang, A Dontabhaktuni, J D Schwartz, J Cosaert, J M Mehnert |
Journal | Investigational new drugs
(Invest New Drugs)
Vol. 33
Issue 2
Pg. 450-62
(Apr 2015)
ISSN: 1573-0646 [Electronic] United States |
PMID | 25749986
(Publication Type: Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antibodies, Monoclonal
- Antibodies, Monoclonal, Humanized
- Antineoplastic Agents
- cixutumumab
- Receptor, IGF Type 1
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Topics |
- Adult
- Aged
- Antibodies, Monoclonal
(administration & dosage, adverse effects, pharmacokinetics)
- Antibodies, Monoclonal, Humanized
- Antineoplastic Agents
(administration & dosage, adverse effects, pharmacokinetics)
- Area Under Curve
- Female
- Half-Life
- Humans
- Male
- Maximum Tolerated Dose
- Metabolic Clearance Rate
- Middle Aged
- Neoplasms
(drug therapy)
- Receptor, IGF Type 1
(antagonists & inhibitors)
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