A phase II multicenter study of L-alanosine, a potent inhibitor of adenine biosynthesis, in patients with MTAP-deficient cancer

Kindler, Hedy Lee; Burris, Howard A.; Sandler, Alan B.; Oliff, Ira Anton

doi:10.1007/s10637-008-9160-1

Cited by 79Biochemical and Molecular ResearchAdenosine and Purinergic SignalingLung Cancer Treatments and Mutations

A phase II multicenter study of L-alanosine, a potent inhibitor of adenine biosynthesis, in patients with MTAP-deficient cancer

Kindler, Hedy Lee, Burris, Howard A., Sandler, Alan B., Oliff, Ira Anton·2009·Investigational New Drugs

DOI 10.1007/s10637-008-9160-1

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Abstract

Objective Methylthioadenosine phosphorylase (MTAP)-deficient tumors are dependent on the de novo purine synthesis pathway. These cancers are potential targets for selective chemotherapy with inhibitors of de novo adenine synthesis such as L-alanosine [L-2-amino-3-(N-hydroxy-N-nitrosamino) propionic acid]. This phase II study was designed to evaluate the efficacy and safety of L-alanosine in patients with MTAP-deficient solid tumors.Methods Patients with mesothelioma, non-small cell lung cancer (NSCLC), soft tissue sarcoma, osteosarcoma, or pancreatic cancer whose tumors were MTAP deficient by immunohistochemistry were eligible. Patients received L-alanosine at a starting dose of 80 mg/m(2) by continuous intravenous infusion daily for 5 days every 21 days. Computed tomography scans or magnetic resonance imaging were performed every 3 cycles.Results 65 patients (16 mesothelioma, 13 NSCLC, 15 soft tissue sarcoma, 7 osteosarcoma, 14 pancreatic cancer) were enrolled at 19 centers; 55 were evaluable for response. There were no objective responses; 24% had s disease, including 2 patients with mesothelioma who had prolonged stable disease lasting 7.5 and 15.2 months, respectively. Grade 3/4 toxicities included mucositis 11%, fatigue 6%, nausea 3%, and renal failure 1.5%.Conclusion At this dose and schedule, L-alanosine was ineffective in patients with advanced MTAP-deficient tumors.

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L-alanosine was clinically ineffective in patients with advanced MTAP-deficient tumors in a Phase II trial.
“but was found to be clinically ineffective in patients with advanced MTAP-deficient tumors in a Phase II trial (Kindler et al., 2009).”
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Authors: Kindler, H. L., Burris, H. A., Sandler, A. B., & Oliff, I. A.
Affiliations: University of Chicago (US)
Sarah Cannon (US)
Vanderbilt-Ingram Cancer Center (US)
Illinois CancerCare (US)
Corresponding author: Kindler, Hedy Lee
ORCID: Kindler, Hedy Lee
Burris, Howard A.
Sandler, Alan B.
Venue: Investigational New Drugs
Publisher: Springer Science and Business Media LLC
Published: 2008-07-11
Volume: 27
Issue: 1
Pages: 75-81
ISSN: 0167-6997 (ISSN-L)
1573-0646
DOI: 10.1007/s10637-008-9160-1
OpenAlex: W1998628096
Cited by: 79
References: 28
Citations by year: 2026: 2 · 2025: 2 · 2024: 4 · 2023: 10 · 2022: 6 · 2021: 4 · 2020: 3 · 2019: 8 · 2018: 2 · 2017: 4 · 2016: 6 · 2015: 2 · 2014: 3 · 2012: 8
FWCI: 2.05
Type: journal article
Language: en
Open access: closed
Licence: www.springernature.com/gp/researchers/text-and-data-mining (tdm)
www.springernature.com/gp/researchers/text-and-data-mining (vor)
Locations: Investigational New Drugs (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Molecular Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Adenosine and Purinergic Signaling
Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
Keywords: MTAP deficiency, mesothelioma, non-small cell lung cancer, soft tissue sarcoma, osteosarcoma, pancreatic cancer, stable disease, chemotherapy toxicity, renal failure
MeSH terms: Adenine, Adolescent, Adult, Aged, Alanine, Antimetabolites, Antineoplastic, Drug Administration Schedule, Female, Humans, Male, Neoplasms, Purine-Nucleoside Phosphorylase

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A phase II multicenter study of L-alanosine, a potent inhibitor of adenine biosynthesis, in patients with MTAP-deficient cancer

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