ArticleAutophagy2014
Phase I trial of hydroxychloroquine with dose-intense temozolomide in patients with advanced solid tumors and melanoma.
Article 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 NCT04353037 (PATCH 2 & 3), which is not on this map. Cited by 227 papers, 1 of them a synthesis 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.
PATCH 2 & 3: (Prevention and Treatment of COVID-19 With Hydroxychloroquine) A Double-blind Placebo Controlled Randomized Trial of Hydroxychloroquine in the Prevention and Treatment of COVID-19
Who cites it
227 citing papers in PubMed, 1 synthesis or guideline pooled it, 358 citations in OpenAlex.
- Targeting Autophagy in Cancer: Update on Clinical Trials and Novel Inhibitors.International journal of molecular sciences · 2017Pooled it
- A Phase II Open-Label Trial of Binimetinib and Hydroxychloroquine in Patients With Advanced KRAS-Mutant Non-Small Cell Lung Cancer.The oncologist · 2023Trial
- BAMM (BRAF Autophagy and MEK Inhibition in Melanoma): A Phase I/II Trial of Dabrafenib, Trametinib, and Hydroxychloroquine in Advanced BRAFV600-mutant Melanoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Trial
- Trial
- Effect of High vs Low Doses of Chloroquine Diphosphate as Adjunctive Therapy for Patients Hospitalized With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection: A Randomized Clinical Trial.JAMA network open · 2020Trial
- 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
- Safety and Biologic Response of Pre-operative Autophagy Inhibition in Combination with Gemcitabine in Patients with Pancreatic Adenocarcinoma.Annals of surgical oncology · 2015Trial
- Drugging small-molecule compounds in autophagy-dependent cell death to overcome cancer therapy resistance.Apoptosis : an international journal on programmed cell death · 2026Review
- Emerging perspectives in proteostasis: bridging mechanisms and therapeutics for human diseases.Signal transduction and targeted therapy · 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
- Autophagy-Apoptosis Crosstalk in Cancer: Mechanisms, Signaling Pathways, and Therapeutic Targeting.Cancers · 2026Review
- Photocaged Chloroquine Derivatives for the Light-Dependent Inhibition of Autophagy in Cancer Stem Cells.ACS chemical biology · 2026Article
- Annexin A1 triggers autophagy to orchestrate radioiodine resistance in thyroid cancer via upregulating HMGB1.Cancer cell international · 2026Article
- The multifaceted functions of selective autophagy in cancer: molecular basis, consequences, and clinical prospects.Molecular cancer · 2026Review
- Crosstalk Between Autophagy and Paraptosis: A New Frontier in Cancer Therapy.International journal of molecular sciences · 2026Review
- Autophagy in Cancer: Context-Dependent Regulation and Precision Nanomedicine-Enabled Therapeutic Targeting.Biomedicines · 2026Review
- Article
- Autophagy modulation in gynaecologic oncology: insights into immune regulation and therapeutic potential.Frontiers in immunology · 2026Review
- Innovative horizons: harnessing drug repositioning for targeted therapeutics in colorectal cancer.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- The Expendables: Overlooked Medications with Anti-Cancer Properties.Current oncology reports · 2025Review
167 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 5 institutions in 1 country.
Funding
Abstract
Blocking autophagy with hydroxychloroquine (HCQ) augments cell death associated with alkylating chemotherapy in preclinical models. This phase I study evaluated the maximum tolerated dose (MTD), safety, preliminary activity, pharmacokinetics, and pharmacodynamics of HCQ in combination with dose-intense temozolomide (TMZ) in patients with advanced solid malignancies. Forty patients (73% metastatic melanoma) were treated with oral HCQ 200 to 1200 mg daily with dose-intense oral TMZ 150 mg/m (2) daily for 7/14 d. This combination was well tolerated with no recurrent dose-limiting toxicities observed. An MTD was not reached for HCQ and the recommended phase II dose was HCQ 600 mg twice daily combined with dose-intense TMZ. Common toxicities included grade 2 fatigue (55%), anorexia (28%), nausea (48%), constipation (20%), and diarrhea (20%). Partial responses and stable disease were observed in 3/22 (14%) and 6/22 (27%) patients with metastatic melanoma. In the final dose cohort 2/6 patients with refractory BRAF wild-type melanoma had a near complete response, and prolonged stable disease, respectively. A significant accumulation in autophagic vacuoles (AV) in peripheral blood mononuclear cells was observed in response to combined therapy. Population pharmacokinetics (PK) modeling, individual PK simulations, and PK-pharmacodynamics (PD) analysis identified a threshold HCQ peak concentration that predicts therapy-associated AV accumulation. This study indicates that the combination of high-dose HCQ and dose-intense TMZ is safe and tolerable, and is associated with autophagy modulation in patients. Prolonged stable disease and responses suggest antitumor activity in melanoma patients, warranting further studies of this combination, or combinations of more potent autophagy inhibitors and chemotherapy in melanoma.
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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.