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Am J Clin Oncol. 2019 Nov;42(11):862-869. doi: 10.1097/COC.0000000000000611.

Phase I Study of IGF-Methotrexate Conjugate in the Treatment of Advanced Tumors Expressing IGF-1R.

Author information

1
Department of Medicine, Division of Hematology/Oncology.
2
Departments of Pathology.
3
Gynecology-Oncology.
4
Division of Epidemiology and Biostatistics School of Public Health.
5
Department of Pharmacy Practice, College of Pharmacy.
6
Oncology Clinical Trials Office, University of Illinois at Chicago, Chicago, IL.
7
IGF Oncology LLC.
8
HealthPartners Regions Cancer Care Center, St Paul, MN.

Abstract

OBJECTIVES:

Insulin-like growth factor-methotrexate (IGF-MTX) is a conjugate of methotrexate and 765IGF, a variant of IGF-1 with high affinity for insulin-like growth factor type 1 receptor. The study aim was to determine the maximum tolerated dose of IGF-MTX in refractory solid organ and hematologic malignancies expressing insulin-like growth factor type 1 receptor.

MATERIALS AND METHODS:

This phase I trial used a modified toxicity probability interval design with 5 cohort dose levels, and expansion cohort at maximum tolerated dose. IGF-MTX was given intravenously over 90 minutes on days 1, 8, and 15 of a 28-day cycle.

RESULTS:

A total of 17 patients were enrolled. The highest tolerated dose tested was 0.80 µEq/kg with dose-limiting toxicity of grade 3 hypoglycemia. Drug-related grade 3 and 4 toxicities included abdominal pain (26%), hypoglycemia (10%), and hypotension (10%). Of the 15 evaluable for response, 3 patients (20%) had stable disease, including the patient with Hodgkin lymphoma with stable disease for 12 cycles of therapy. IGF-MTX concentrations declined rapidly, with half-lives of 5.2 to 14 minutes for the initial distribution phase and 6.5 to 7.5 hours for the terminal elimination phase. Higher IGF-R1 expression did not correlate with better outcome.

CONCLUSIONS:

IGF-MTX is well tolerated. IGF-MTX pharmacokinetics suggest rapid cellular uptake. The activity of IGF-MTX in Hodgkin lymphoma should be explored.

PMID:
31633515
DOI:
10.1097/COC.0000000000000611
[Indexed for MEDLINE]

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