Patient with Recurrent Glioblastoma Responding Favorably to Ketogenic Diet Combined with Intranasal Delivery of Perillyl Alcohol: A Case Report and Literature Review

Santos, Juliana; Cruz, Wanise Maria Souza Da; Schönthal, Axel H.; Salazar, Marcela d’Alincourt; Fontes, Cristina Asvolinsque Pantaleão; Quirico-Santos, Thereza; Fonseca, Clóvis Orlando da

doi:10.1055/s-0037-1605588

Cited by 2 publications

(4 citation statements)

References 38 publications

(54 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A list of relevant KD studies published in peer-reviewed journals is given in Table 1, and Fig. 3 shows their chronological appearance relating to Brünings’ publications 7 , 10, 11, 12, 13, 14 , 32 , 34 , 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65. It took almost half a century after Brünings’ first publication until what is generally considered the first clinical study treating cancer patients with a KD was published (Fearon et al.…”

Section: Discussionmentioning

confidence: 99%

“…2017Controlled case study (registered)542 (37–69)Low and high grade gliomaNone (1), bevacizumab (4)8 (2–31) monthsNoYes (4:1 KetoCal ® )İyikesici et al 60 2017Case study129Stage IV triple-negative breast cancerMetabolically (insulin-) supported CT, hyperbaric oxygen, hyperthermia1 yearNoNoSantos et al 61 2017Case study154Recurrent glioblastomaIntranasal perillylalcohol3 monthsNoNoTóth & Clemens 62 2017Case study162Rectal cancerRT (6 weeks), then none24 monthsNoNoZahra et al 13 …”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Wilhelm Brünings' forgotten contribution to the metabolic treatment of cancer utilizing hypoglycemia and a very low carbohydrate (ketogenic) diet

Klement

2019

Journal of Traditional and Complementary Medicine

View full text Add to dashboard Cite

The growing interest in the alterations of tumor cell metabolism and their possible therapeutic exploitation also spurred new complementary and integrative approaches such as treating patients with a ketogenic diet (KD). KDs aim at inhibiting glycolytic tumor metabolism and growth, and have therefore been proposed as adjuncts not only to standard-of-care, but also to other therapies targeting tumor metabolism. Here I describe the life and forgotten work of one of the earliest researchers who realized the importance of altered tumor cell metabolism and its possible exploitation through metabolic modifications: Wilhelm Brünings. Brünings was a German natural scientist and physician famous for his innovative contributions to the fields of physiology and otorhinolaryngology. Based on the findings of Otto Warburg and his physiological reasoning he started to experiment with insulin administration and KDs in his patients with head and neck cancers, aiming to maximally lower blood glucose concentrations. He obtained encouraging short-term results, although most tumors became refractory to treatment after several weeks. His pioneering work is worth revisiting, especially for an international readership that may be unaware of his efforts, as hypoglycemic treatments, including the use of insulin injections and KDs, are currently being re-investigated as complementary and integrative cancer treatments.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Wilhelm Brünings' forgotten contribution to the metabolic treatment of cancer utilizing hypoglycemia and a very low carbohydrate (ketogenic) diet

Klement

2019

Journal of Traditional and Complementary Medicine

View full text Add to dashboard Cite

show abstract

“…A recently published case study [127] reported on a patient with recurrent GB who responded favorably to KD combined with intranasal POH. This patient had undergone surgery, followed by standard chemoradiation (6 weeks of radiation plus temozolomide), followed by 3 cycles of adjuvant temozolomide.…”

Section: Perillyl Alcoholmentioning

confidence: 99%

“…At the same time, there was some weight loss, along with a small increase in muscle mass. It was concluded that this therapeutic regimen was very well tolerated and appeared to have therapeutic benefit [127].…”

Section: Perillyl Alcoholmentioning

confidence: 99%

Intranasal Perillyl Alcohol for Glioma Therapy: Molecular Mechanisms and Clinical Development

Chen

Fonseca

Schönthal

2018

IJMS

Self Cite

View full text Add to dashboard Cite

Intracranial malignancies, such as primary brain cancers and brain-localized metastases derived from peripheral cancers, are particularly difficult to treat with therapeutic agents, because the blood-brain barrier (BBB) effectively minimizes brain entry of the vast majority of agents arriving from the systemic circulation. Intranasal administration of cancer drugs has the potential to reach the brain via direct nose-to-brain transport, thereby circumventing the obstacle posed by the BBB. However, in the field of cancer therapy, there is a paucity of studies reporting positive results with this type of approach. A remarkable exception is the natural compound perillyl alcohol (POH). Its potent anticancer activity was convincingly established in preclinical studies, but it nonetheless failed in subsequent clinical trials, where it was given orally and displayed hard-to-tolerate gastrointestinal side effects. Intriguingly, when switched to intranasal delivery, POH yielded highly promising activity in recurrent glioma patients and was well tolerated. As of 2018, POH is the only intranasally delivered compound in the field of cancer therapy (outside of cancer pain) that has advanced to active clinical trials. In the following, we will introduce this compound, summarize its molecular mechanisms of action, and present the latest data on its clinical evaluation as an intranasally administered agent for glioma.

show abstract

Patient with Recurrent Glioblastoma Responding Favorably to Ketogenic Diet Combined with Intranasal Delivery of Perillyl Alcohol: A Case Report and Literature Review

Cited by 2 publications

References 38 publications

Wilhelm Brünings' forgotten contribution to the metabolic treatment of cancer utilizing hypoglycemia and a very low carbohydrate (ketogenic) diet

Wilhelm Brünings' forgotten contribution to the metabolic treatment of cancer utilizing hypoglycemia and a very low carbohydrate (ketogenic) diet

Intranasal Perillyl Alcohol for Glioma Therapy: Molecular Mechanisms and Clinical Development

Contact Info

Product

Resources

About