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Cited by 190Glioma Diagnosis and TreatmentNanoparticle-Based Drug DeliveryDrug Transport and Resistance Mechanisms

The DOI matches its Crossref record; 50 of the 51 references it cites were found in a registry or an index.

Phase I Study of GRN1005 in Recurrent Malignant Glioma

Drappatz, Jan, Brenner, Andrew, Wong, Eric T., Eichler, April, Schiff, David, Groves, Morris D., Mikkelsen, Tom, Rosenfeld, Steve, Sarantopoulos, John, Meyers, Christina A., Fielding, Robert M., Elian, Kelly, Wang, Xiaolin, Lawrence, Betty, Shing, Mona, Kelsey, Stephen, Castaigne, Jean Paul, Wen, Patrick Y.·2013·Clinical Cancer Research
DOI 10.1158/1078-0432.ccr-12-2481
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Abstract

PURPOSE: GRN1005 is a peptide-drug conjugate with the ability to penetrate the blood-brain barrier (BBB) and tumor cells by targeting the low-density lipoprotein receptor-related protein-1. We conducted a first-in-human phase I trial of GRN1005 in patients with recurrent glioma. METHODS: Patients received GRN1005 by intravenous infusion every 3 weeks. Doses were escalated using a modified Fibonacci scheme. Study objectives included safety, tolerability, identification of the maximum tolerated dose (MTD), pharmacokinetics, and preliminary evidence of efficacy. Tumor extracted from patients undergoing surgery following administration of GRN1005 was analyzed to determine whether therapeutic concentrations of GRN1005 were achieved. RESULTS: Sixty-three patients received GRN1005 at doses of 30 to 700 mg/m(2) every 3 weeks. Therapy was well tolerated with neutropenia, leucopenia, and fatigue as the most frequent drug-associated grade 3/4 or higher toxicities. The MTD was 650 mg/m(2) every 3 weeks. Dose-limiting toxicities were grade 3 mucositis and grade 4 neutropenia. There was no evidence of central nervous system toxicity or antibody production. Pharmacokinetic analysis showed that exposure to GRN1005 was dose proportional. We observed one complete and two partial responses. Eight of 27 patients dosed ≥ 420 mg/m(2) had stable disease, which lasted a median of 51 days. Therapeutic concentrations of GRN1005 and free paclitaxel were shown in tumor tissue of surgical patients dosed with ≥ 200 mg/m(2). CONCLUSION: GRN1005 delivers paclitaxel across the BBB and achieves therapeutic concentrations in tumor tissue. It has similar toxicity to paclitaxel and appears to have activity in recurrent glioma. The recommended phase II dose is 650 mg/m(2) every 3 weeks.

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Crossref · 10.1158/1078-0432.ccr-12-2481

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Metadata

Authors
Drappatz, J., Brenner, A., Wong, E. T., Eichler, A., Schiff, D., Groves, M. D., Mikkelsen, T., Rosenfeld, S., Sarantopoulos, J., Meyers, C. A., Fielding, R. M., Elian, K., Wang, X., Lawrence, B., Shing, M., Kelsey, S., Castaigne, J. P., & Wen, P. Y.
Affiliations
Brigham and Women's Hospital (US)
ORCID
Venue
Clinical Cancer Research
Publisher
American Association for Cancer Research (AACR)
Published
2013-03-14
Volume
19
Issue
6
Pages
1567-1576
ISSN
  • 1078-0432 (ISSN-L)
  • 1557-3265
DOI
10.1158/1078-0432.ccr-12-2481
OpenAlex
W2111631341
Cited by
190
References
51
Citations by year
2026: 11 · 2025: 16 · 2024: 15 · 2023: 16 · 2022: 22 · 2021: 15 · 2020: 17 · 2019: 19 · 2018: 12 · 2017: 6 · 2016: 15 · 2015: 18 · 2014: 7 · 2013: 1
FWCI
6.73
Type
journal article
Language
en
Open access
closed
Locations
  • Clinical Cancer Research (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Oncology › Glioma Diagnosis and Treatment
  • Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
  • Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
Keywords
recurrent malignant glioma, peptide-drug conjugates, LDL receptor-related protein 1, blood-brain barrier penetration, paclitaxel, maximum tolerated dose, pharmacokinetics, dose-limiting toxicity
MeSH terms
Adult, Aged, Antineoplastic Agents, Blood-Brain Barrier, Dose-Response Relationship, Drug, Drug Administration Schedule, Female, Glioma, Humans, Male, Middle Aged, Neoplasm Recurrence, Local, Neoplasm Staging, Peptides, Paclitaxel, Maximum Tolerated Dose, Drug-Related Side Effects and Adverse Reactions

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