Feasibility study of metabolically supported chemotherapy with weekly carboplatin/paclitaxel combined with ketogenic diet, hyperthermia and hyperbaric oxygen therapy in metastatic non-small cell lung cancer

Iyikesici, M. S.

doi:10.1080/02656736.2019.1589584

Cited by 53 publications

(37 citation statements)

References 86 publications

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“…We also have some evidence for synergistic effects between KDs and other therapies, in accordance with predictions from animal studies [2]. In stage IV non-small cell lung cancer patients a KD combined with hyperthermia, hyperbaric oxygen, and short-term fasting prior to chemotherapy resulted in a 3 − 8 times longer overall and progression-free survival than expected from other studies applying the same type of chemotherapy [24]. In metastasized pancreatic cancer patients, the same combination of complementary treatments together with gemcitabine or FOLFIRINOX chemotherapy resulted in a median overall and progression-free survival of 15.8 months (95% CI, 10.5-21.1) and 12.9 months (95% CI, 11.2-14.6), respectively [25].…”

Section: Current State Of the Researchsupporting

confidence: 86%

Addressing the controversial role of ketogenic diets in cancer treatment

Klement

2020

Expert Review of Anticancer Therapy

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Section: Current State Of the Researchsupporting

confidence: 86%

Addressing the controversial role of ketogenic diets in cancer treatment

Klement

2020

Expert Review of Anticancer Therapy

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“…Rapamycin was selected for the current animal study because it a) has the potential to be a successful anti-cancer drug when administered at doses known to be normo-glycemic in mice b) it may yet have utility in humans and c) has been an FDA approved drug since 1999 [11]. The principle of combining a ketogenic diet with other forms of anti-cancer chemotherapies for widely metastatic disease has been reported to have additive effects in mice [12] [13] [14], as well as in limited human studies [4] [15] [16] [17]. As above, rapamycin is not expected to induce hyperglycemia in our mouse model and we wished to determine if a KD would exert its cytotoxic effects even in the absence of hyperglycemia.…”

Section: Introductionmentioning

confidence: 99%

The Effect of a Ketogenic Diet and Synergy with Rapamycin in a Mouse Model of Breast Cancer

Zou

Fineberg

Pearlman

et al. 2020

Preprint

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14 Background: The effects of diet in cancer, in general, and breast cancer in particular, 15 are not well understood. Insulin inhibition in ketogenic, high fat diets, modulate 16 downstream signaling molecules and are postulated to have therapeutic benefits.17 Obesity and diabetes have been associated with higher incidence of breast cancer.18 Addition of anti-cancer drugs together with diet is also not well studied.19 Methods: Two diets, one ketogenic, the other standard mouse chow, were tested in a 20 spontaneous breast cancer model in mice. The diets were implemented either with or 21 without added rapamycin, an mTOR inhibitor and potential anti-cancer drug.22 Results: Blood glucose and insulin concentrations in mice ingesting the ketogenic diet 23 (KD) were significantly lower, whereas beta hydroxybutyrate (BHB) levels were 24 significantly higher, respectively, than in mice on the standard diet (SD). Growth of 25 primary breast tumors and lung metastases were inhibited, and lifespans were longer in 26 the KD mice compared to mice on the SD (p<0.005). Rapamycin improved survival in 27 both mouse diet groups, but when combined with the KD was more effective than when 28 combined with the SD.29 Conclusions: The study provides proof of principle that a ketogenic diet a) results in 30 serum insulin reduction and ketosis in a spontaneous breast cancer mouse model; b) 31 can serve as a therapeutic anti-cancer agent; and c) can enhance the effects of 32 rapamycin, an anti-cancer drug, permitting dose reduction for comparable effect.33 Further, the ketogenic diet in this model produces superior cancer control than standard 34 mouse chow whether with or without added rapamycin. 36 Introduction 37Insulin inhibition by a ketogenic diet has been shown to slow cancer growth and 38 prolong survival in animal models and has shown safety and feasibility in small pilot 39 studies in humans [1], [2] [3] [4] . We previously demonstrated in a pilot study of ten 40 people with diverse, metastatic PET positive cancers that higher levels of ketosis 41 correlated with stability vs. disease progression [5]. The full potential of ketosis in 42 cancer therapy, however, may reside in its potential to synergize with anti-cancer drugs 43 and other modalities of treatment. Increased overall efficacy may permit lower drug 44 doses, thereby reducing their toxicities and side effects. Accordingly, it may be possible 45 that the overall improvement in therapy will result in extended survival with a better 46 quality of life. 47 An understanding of ketogenic diets (KD) in cancer is limited at this point but it 48 seems unlikely that KDs by themselves can control all the features of the oncogenic 49 state. There is much interest, therefore, in the possibility of synergy with other drugs or 50 other therapies. Hsieh, et al., for example, demonstrated that a squamous cell 51 carcinoma that over expressed GLUT1 receptors showed attenuated growth when 52 animals were on a KD [6]. There was, however, little regression of tumors. The addition 53 of th...

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“…A failure to continue with the KMT protocol was considered responsible in part for her tumor recurrence (154). Nevertheless, a subsequent clinical study showed that a ketogenic diet combined with carboplatin/paclitaxel, hyperthermia, and hyperbaric oxygen therapy significantly improved progressionfree and overall survival in patients with advanced non-small cell lung cancer (211). Currently, neoadjuvant therapies are commonly prescribed for a subset of invasive or late-stage cancers, including breast cancers.…”

Section: Kmt As a Complementary Or Alternative To Socmentioning

confidence: 99%

Consideration of Ketogenic Metabolic Therapy as a Complementary or Alternative Approach for Managing Breast Cancer

et al. 2020

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Breast cancer remains as a significant cause of morbidity and mortality in women. Ultrastructural and biochemical evidence from breast biopsy tissue and cancer cells shows mitochondrial abnormalities that are incompatible with energy production through oxidative phosphorylation (OxPhos). Consequently, breast cancer, like most cancers, will become more reliant on substrate level phosphorylation (fermentation) than on oxidative phosphorylation (OxPhos) for growth consistent with the mitochondrial metabolic theory of cancer. Glucose and glutamine are the prime fermentable fuels that underlie therapy resistance and drive breast cancer growth through substrate level phosphorylation (SLP) in both the cytoplasm (Warburg effect) and the mitochondria (Q-effect), respectively. Emerging evidence indicates that ketogenic metabolic therapy (KMT) can reduce glucose availability to tumor cells while simultaneously elevating ketone bodies, a non-fermentable metabolic fuel. It is suggested that KMT would be most effective when used together with glutamine targeting. Information is reviewed for suggesting how KMT could reduce systemic inflammation and target tumor cells without causing damage to normal cells. Implementation of KMT in the clinic could improve progression free and overall survival for patients with breast cancer.

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Feasibility study of metabolically supported chemotherapy with weekly carboplatin/paclitaxel combined with ketogenic diet, hyperthermia and hyperbaric oxygen therapy in metastatic non-small cell lung cancer

Cited by 53 publications

References 86 publications

Addressing the controversial role of ketogenic diets in cancer treatment

Addressing the controversial role of ketogenic diets in cancer treatment

The Effect of a Ketogenic Diet and Synergy with Rapamycin in a Mouse Model of Breast Cancer

Consideration of Ketogenic Metabolic Therapy as a Complementary or Alternative Approach for Managing Breast Cancer

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