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Systematic Review

Systematic Review of Gossypol/AT-101 in Cancer Clinical Trials

1
Department of Nutritional Biochemistry, Institute of Nutritional Sciences, University of Hohenheim, 70599 Stuttgart, Germany
2
Institute of Nutritional Medicine and Prevention, University of Hohenheim, 70599 Stuttgart, Germany
3
Department of Internal Medicine VIII, University Hospital Tuebingen, 72076 Tuebingen, Germany
4
German Cancer Consortium (DKTK), DKFZ Partner Site, 72076 Tuebingen, Germany
5
Department of Vegetative and Clinical Physiology, Institute of Physiology, University of Tuebingen, 72074 Tuebingen, Germany
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Célia Cabral
Pharmaceuticals 2022, 15(2), 144; https://doi.org/10.3390/ph15020144
Received: 15 December 2021 / Revised: 17 January 2022 / Accepted: 21 January 2022 / Published: 26 January 2022
(This article belongs to the Section Natural Products)
The potential of gossypol and of its R-(−)-enantiomer (R-(−)-gossypol acetic acid, AT-101), has been evaluated for treatment of cancer as an independent agent and in combination with standard chemo-radiation-therapies, respectively. This review assesses the evidence for safety and clinical effectiveness of oral gossypol/AT-101 in treating various types of cancer. The databases PubMed, MEDLINE, Cochrane, and ClinicalTrials.gov were examined. Phase I and II trials as well as single arm and randomized trials were included in this review. Results were screened to determine if they met inclusion criteria and then summarized using a narrative approach. A total of 17 trials involving 759 patients met the inclusion criteria. Overall, orally applied gossypol/AT-101 at low doses (30 mg daily or lower) was determined as well tolerable either as monotherapy or in combination with chemo-radiation. Adverse events should be strictly monitored and were successfully managed by dose-reduction or treating symptoms. There are four randomized trials, two performed in patients with advanced non-small cell lung cancer, one in subjects with head and neck cancer, and one in patients with metastatic castration-resistant prostate cancer. Thereby, standard chemotherapy (either docetaxel (two trials) or docetaxel plus cisplatin or docetaxel plus prednisone) was tested with and without AT-101. Within these trials, a potential benefit was observed in high-risk patients or in some patients with prolongation in progression-free survival or in overall survival. Strikingly, the most recent clinical trial combined low dose AT-101 with docetaxel, fluorouracil, and radiation, achieving complete responses in 11 of 13 patients with gastroesophageal carcinoma (median duration of 12 months) and a median progression-free survival of 52 months. The promising results shown in subsets of patients supports the need of further specification of AT-101 sensitive cancers as well as for the establishment of effective AT-101-based therapy. In addition, the lowest recommended dose of gossypol and its precise toxicity profile need to be confirmed in further studies. Randomized placebo-controlled trials should be performed to validate these data in large cohorts. View Full-Text
Keywords: oral gossypol; AT-101; clinical trial; cancer; oncologic patients oral gossypol; AT-101; clinical trial; cancer; oncologic patients
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MDPI and ACS Style

Renner, O.; Mayer, M.; Leischner, C.; Burkard, M.; Berger, A.; Lauer, U.M.; Venturelli, S.; Bischoff, S.C. Systematic Review of Gossypol/AT-101 in Cancer Clinical Trials. Pharmaceuticals 2022, 15, 144. https://doi.org/10.3390/ph15020144

AMA Style

Renner O, Mayer M, Leischner C, Burkard M, Berger A, Lauer UM, Venturelli S, Bischoff SC. Systematic Review of Gossypol/AT-101 in Cancer Clinical Trials. Pharmaceuticals. 2022; 15(2):144. https://doi.org/10.3390/ph15020144

Chicago/Turabian Style

Renner, Olga, Mascha Mayer, Christian Leischner, Markus Burkard, Alexander Berger, Ulrich M. Lauer, Sascha Venturelli, and Stephan C. Bischoff. 2022. "Systematic Review of Gossypol/AT-101 in Cancer Clinical Trials" Pharmaceuticals 15, no. 2: 144. https://doi.org/10.3390/ph15020144

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