Trial reportAutophagy2014
A phase I/II trial of hydroxychloroquine in conjunction with radiation therapy and concurrent and adjuvant temozolomide in patients with newly diagnosed glioblastoma multiforme.
Trial report in Autophagy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00486603 (A Phase I/II Trial of Hydroxychloroquine in Conjunction With Radiation Therapy and Concurrent and Adjuvant Temozolomide in Patients With Newly Diagnosed Glioblastoma Multiforme), which is not on this map. Cited by 329 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Phase I/II Trial of Hydroxychloroquine in Conjunction With Radiation Therapy and Concurrent and Adjuvant Temozolomide in Patients With Newly Diagnosed Glioblastoma Multiforme
Who cites it
329 citing papers in PubMed, 2 syntheses or guidelines pooled it, 521 citations in OpenAlex.
- Enhancing radiation sensitivity in malignant brain tumors with chloroquine: a systematic review.Journal of neuro-oncology · 2025Pooled it
- Congress of neurological surgeons systematic review and evidence-based guidelines update on the role of emerging developments in the management of newly diagnosed glioblastoma.Journal of neuro-oncology · 2020Pooled it
- Autophagy Inhibition to Augment mTOR Inhibition: a Phase I/II Trial of Everolimus and Hydroxychloroquine in Patients with Previously Treated Renal Cell Carcinoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019Trial
- Autophagy modulation in cancer.Nature reviews. Drug discovery · 2026Review
- Harnessing Repurposed Drugs to Enhance Temozolomide Efficacy in Glioblastoma.Cancer reports (Hoboken, N.J.) · 2026Review
- Autophagy in Melanoma: Molecular Mechanisms and Therapeutic Perspectives.International journal of molecular sciences · 2026Review
- Targeting lysosome-dependent cell death in cancer: towards therapeutic strategies.Biomarker research · 2026Review
- Targeting programmed cell death: a novel therapeutic paradigm for cancer based on mode-of-death classification.Apoptosis : an international journal on programmed cell death · 2026Review
- Dual-responsive peptide nanoplatform for improved lung cancer therapy via the synergistic suppression of autophagy and drug efflux.Materials today. Bio · 2026Article
- Autophagy is essential for survival and function of polyploid giant cancer cells under therapeutic stress.Cancer letters · 2026Article
- Photocaged Chloroquine Derivatives for the Light-Dependent Inhibition of Autophagy in Cancer Stem Cells.ACS chemical biology · 2026Article
- The CHI3L1 protein plays role as a protecting factor against autophagy in glioblastoma cells.Apoptosis : an international journal on programmed cell death · 2026Article
- Structure-Activity Relationship Studies Enable Optimization of a Small-Molecule Autophagy Activator and Evaluation of Effects on Cell Death Pathways.ACS pharmacology & translational science · 2026Article
- The multifaceted functions of selective autophagy in cancer: molecular basis, consequences, and clinical prospects.Molecular cancer · 2026Review
- A small molecule targets LIC1 to suppress lung tumor growth by inducing autophagy.Nature chemical biology · 2026Article
- Crosstalk Between Autophagy and Paraptosis: A New Frontier in Cancer Therapy.International journal of molecular sciences · 2026Review
- Overcoming Chemoresistance in Glioblastoma: Mechanisms, Therapeutic Strategies, and Functional Precision Medicine.International journal of molecular sciences · 2026Review
- Effects of Disulfiram and Copper in Combination with Temozolomide on Survival, Tumor Size and Autophagy Markers in an F98 Rat Glioma Model.International journal of molecular sciences · 2026Article
- Unlocking glioma vulnerabilities: targeting regulated cell death pathways for innovative therapies.Cell death discovery · 2026Review
- A bibliometric analysis of global research trends in autophagy and glioblastomas.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
269 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
20 authors at 10 institutions in 1 country.
Funding
Abstract
Preclinical studies indicate autophagy inhibition with hydroxychloroquine (HCQ) can augment the efficacy of DNA-damaging therapy. The primary objective of this trial was to determine the maximum tolerated dose (MTD) and efficacy of HCQ in combination with radiation therapy (RT) and temozolomide (TMZ) for newly diagnosed glioblastoma (GB). A 3 + 3 phase I trial design followed by a noncomparative phase II study was conducted in GB patients after initial resection. Patients received HCQ (200 to 800 mg oral daily) with RT and concurrent and adjuvant TMZ. Quantitative electron microscopy and immunoblotting were used to assess changes in autophagic vacuoles (AVs) in peripheral blood mononuclear cells (PBMC). Population pharmacokinetic (PK) modeling enabled PK-pharmacodynamic correlations. Sixteen phase I subjects were evaluable for dose-limiting toxicities. At 800 mg HCQ/d, 3/3 subjects experienced Grade 3 and 4 neutropenia and thrombocytopenia, 1 with sepsis. HCQ 600 mg/d was found to be the MTD in this combination. The phase II cohort (n = 76) had a median survival of 15.6 mos with survival rates at 12, 18, and 24 mo of 70%, 36%, and 25%. PK analysis indicated dose-proportional exposure for HCQ. Significant therapy-associated increases in AV and LC3-II were observed in PBMC and correlated with higher HCQ exposure. These data establish that autophagy inhibition is achievable with HCQ, but dose-limiting toxicity prevented escalation to higher doses of HCQ. At HCQ 600 mg/d, autophagy inhibition was not consistently achieved in patients treated with this regimen, and no significant improvement in overall survival was observed. Therefore, a definitive test of the role of autophagy inhibition in the adjuvant setting for glioma patients awaits the development of lower-toxicity compounds that can achieve more consistent inhibition of autophagy than HCQ.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.