The DOI matches its Crossref record; 5 of the 5 references it cites were found in a registry or an index.
Phase I trial of hydroxychloroquine with dose-intense temozolomide in patients with advanced solid tumors and melanoma
Open accessAbstract
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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Cites
Radiotherapy Plus Concomitant and Adjuvant Temozolomide for Glioblastoma
Stupp, R., Mason, W. P., van den Bent, M. J., Weller, M., Fisher, B., Taphoorn, M. J. B., Belanger, K., Brandes, A. A., Marosi, C., Bogdahn, U., et al. (2005) · New England Journal of Medicine · doi:10.1056/nejmoa043330 · Cited by 21,807
New Guidelines to Evaluate the Response to Treatment in Solid Tumors
Therasse, P., Arbuck, S. G., Eisenhauer, E. A., Wanders, J., Kaplan, R. S., Rubinstein, L., Verweij, J., Van Glabbeke, M., van Oosterom, A. T., Christian, M. C., et al. (2000) · JNCI: Journal of the National Cancer Institute · doi:10.1093/jnci/92.3.205 · Cited by 15,660
Pancreatic cancers require autophagy for tumor growth
Yang, S., Wang, X., Contino, G., Liesa, M., Sahin, E., Ying, H., Bause, A., Li, Y., Stommel, J. M., Dell'Antonio, G., et al. (2011) · Genes & Development · doi:10.1101/gad.2016111 · Cited by 1,498
Activated Ras requires autophagy to maintain oxidative metabolism and tumorigenesis
Guo, J. Y., Chen, H.-Y., Mathew, R., Fan, J., Strohecker, A. M., Karsli-Uzunbas, G., Kamphorst, J. J., Chen, G., Lemons, J. M. S., Karantza, V., et al. (2011) · Genes & Development · doi:10.1101/gad.2016311 · Cited by 1,323
Autophagy Sustains Mitochondrial Glutamine Metabolism and Growth of Braf V600E–Driven Lung Tumors
Strohecker, A. M., Guo, J. Y., Karsli-Uzunbas, G., Price, S. M., Chen, G. J., Mathew, R., McMahon, M., & White, E. (2013) · Cancer Discovery · doi:10.1158/2159-8290.cd-13-0397 · Cited by 435
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Levy, J. M. M., Towers, C. G., & Thorburn, A. (2017) · Nature Reviews Cancer · doi:10.1038/nrc.2017.53 · Cited by 2,526
Mechanisms of action of hydroxychloroquine and chloroquine:implications for rheumatology
Schrezenmeier, E., & Dörner, T. (2020) · Nature Reviews Rheumatology · doi:10.1038/s41584-020-0372-x · Cited by 1,468
Autophagy in malignant transformation and cancer progression
Galluzzi, L., Pietrocola, F., Bravo‐San Pedro, J. M., Amaravadi, R. K., Baehrecke, E. H., Cecconi, F., Codogno, P., Debnath, J., Gewirtz, D. A., Karantza, V., et al. (2015) · The EMBO Journal · doi:10.15252/embj.201490784 · Cited by 1,182
Self-citationBorba, M. G. S., Val, F. F. A., Sampaio, V. S., Alexandre, M. A. A., Melo, G. C., Brito, M., Mourão, M. P. G., Brito-Sousa, J. D., Baía-da-Silva, D., Guerra, M. V. F., et al. (2020) · JAMA Network Open · doi:10.1001/jamanetworkopen.2020.8857 · Cited by 1,038
Targeting Autophagy in Cancer: Recent Advances and Future Directions
Amaravadi, R. K., Kimmelman, A. C., & Debnath, J. (2019) · Cancer Discovery · doi:10.1158/2159-8290.cd-19-0292 · Cited by 928
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Metadata
- Authors
- Rangwala, R., Leone, R., Chang, Y. C., Fecher, L. A., Schuchter, L. M., Kramer, A., Tan, K.-S., Heitjan, D. F., Rodgers, G., Gallagher, M., Piao, S., Troxel, A. B., Evans, T. L., DeMichele, A. M., Nathanson, K. L., O’Dwyer, P. J., Kaiser, J., Pontiggia, L., Davis, L. E., & Amaravadi, R. K.
- Venue
- Autophagy
- Publisher
- Informa UK Limited
- Published
- 2014-05-20
- Volume
- 10
- Issue
- 8
- Pages
- 1369-1379
- ISSN
- 1554-8627 (ISSN-L)
- 1554-8635
- OpenAlex
- W2055510039
- Cited by
- 367
- References
- 5
- FWCI
- 27.19
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Rangwala, R., Leone, R., Chang, Y. C., Fecher, L. A., Schuchter, L. M., Kramer, A., Tan, K.-S., Heitjan, D. F., Rodgers, G., Gallagher, M., Piao, S., Troxel, A. B., Evans, T. L., DeMichele, A. M., Nathanson, K. L., O’Dwyer, P. J., Kaiser, J., Pontiggia, L., Davis, L. E., & Amaravadi, R. K. (2014). Phase I trial of hydroxychloroquine with dose-intense temozolomide in patients with advanced solid tumors and melanoma. Autophagy. https://doi.org/10.4161/auto.29118
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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