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Metabolically Supported Chemotherapy for Managing End-Stage Breast Cancer: A Complete and Durable Response. Cureus. 2021 Apr 26;13(4).

Abstract

Breast cancer accounts for significant morbidity and mortality worldwide. Currently, treatment options in metastatic breast cancer consist of chemotherapy, along with endocrine, radiation, and/or biological therapies. Although advances in management have improved overall survival times, the treatment options for women with end-stage disease are mostly limited to supportive care.

Herein, we present a case report that highlights the response of a 47-year-old premenopausal woman with end-stage (T4N3M1) breast cancer treated with metabolically supported chemotherapy (MSCT), ketogenic diet (KD), hyperthermia (HT), and hyperbaric oxygen therapy (HBOT). The patient first noticed a right breast mass in late 2016, which was initially evaluated and ruled out as a cyst. Skin ulceration was observed in the region of the suspected cyst in May 2017. Subsequent bilateral breast ultrasound identified masses in both breasts and an enlarged right axillary lymph node. The diagnosis following biopsy was grade 3, estrogen receptor-positive (ER+), progesterone receptor-positive (PR+), human epidermal growth factor receptor 2 negative (HER2-), invasive ductal carcinoma of the breast. Initially, the patient refused to receive conventional chemotherapy because of its potential for side effects and toxicity, but she sought medical treatment in August 2018 following extensive disease progression and deterioration of general health.

On re-evaluation, the patient was considered ineligible for conventional treatment due to her advanced endstage disease, poor performance status (Eastern Cooperative Oncology Group score: 3), and advanced respiratory symptoms. Exploring other options, the patient was admitted to the ChemoThermia Oncology Center, Istanbul, Turkey in November 2018. At that time, the patient weighed 38 kg (body mass index: 18.1 kg/m2) and had extensive metastatic disease with lesions in the brain, lungs, mediastinum, liver, abdomen, and bones that were detected by magnetic resonance imaging of the brain (with contrast) and whole-body (18F)-fluorodeoxyglucose-positron emission tomography-computed tomography. The patient received a sixmonth treatment protocol comprised of MSCT, KD, HT, and HBOT, which eliminated all detectable lesions.

The therapeutic response was sustained for two years with maintenance treatment comprising KD, dietary supplements, and repurposed medications. This single case report presents evidence of a complete and durable response to a treatment protocol combining MSCT and a novel metabolic therapy in a patient withend-stage breast cancer.

 

Survival Outcomes of Metabolically Supported Chemotherapy Combined with Ketogenic Diet, Hyperthermia, and Hyperbaric Oxygen Therapy in Advanced Gastric Cancer. Niger J Clin Pract 2020;23:734-40.

Abstract
Background: Survival outcomes are still far from being satisfactory in patients with advanced gastric cancer, despite availability of novel chemotherapeutic regimens.

Aim: This study evaluated the outcomes of patients with advanced gastric cancer who received chemotherapy along with additional treatment modalities targeting multiple tumor cell vulnerabilities.

Materials and Methods: A total of 24 patients diagnosed with stage III–IV locally advanced or metastatic gastric adenocarcinoma that received metabolically supported chemotherapy (MSCT) combined with ketogenic diet, local hyperthermia, and hyperbaric oxygen therapy (HBOT) between April 2014 and October 2017 were included in this retrospective study. Survival outcomes were evaluated.

Results: In 22 patients (88.0%), complete response was achieved. Mean duration of follow-up was 23.9 ± 12.7 months. Mean overall survival was 39.5 months (95% confidence interval [CI]: 28.1–51.0) and mean progression free survival was 36.5 months (95% CI: 25.7–47.2). No problems were encountered due to fasting, hypoglycemia, ketogenic diethyperthermia or HBOT.

Conclusions: The combination treatment used in this study (MSCT together with a ketogenic diethyperthermia and HBOT) appears to be promising in the treatment of advanced gastric cancer. Further research and comparative clinical trials are warranted to support and standardize this novel treatment protocol.

 

Preliminary results of metabolically supported chemotherapy combined with ketogenic diet, hyperthermia and hyperbaric oxygen therapy in stage II-IV rectal cancer. Arch Clin Exp Med 2020;5(1):16-20.

Abstract
Aim: Systemic chemotherapy is a part of multi-modality treatment in patients with stage II-IV rectal cancer. In particular, patients not eligible for curative resection at the time of diagnosis require more efficient approaches to improve outcomes. Metabolically supported chemotherapy (MSCT) is a novel approach targeting dysregulated energy mechanism of the tumor cell. This study aimed to examine the efficacy of MSCT combined with ketogenic diet, hyperthermia and hyperbaric oxygen therapy (HBOT) in patients with stage II-IV rectal cancer not eligible for surgery at baseline.

Methods: Twenty-one patients diagnosed with stage II-IV rectal carcinoma who received metabolically supported chemotherapy (MSCT) combined with ketogenic diet, hyperthermia and HBOT were included. Firstline chemotherapy regimen was oxaliplatin-based, whereas second line regimen was irinotecan-based. Overall survival and progression-free survival were estimated.

Results: Mean duration of follow-up was 33.3±22.0 months. Mean overall survival was 58.6 months (95% CI, 43.3 – 73.9) and corresponding figure for progression-free survival was 45.1 months (95% CI, 28.9-61.2). Mean overall survival for patients with metastatic disease was 35.7 months. Multivariate analysis identified male gender and stage IV disease as independent predictors of worse progression free survival. No other parameter effected survival outcomes.

Conclusion: Findings of this study are promising for potential use of this novel combinatorial protocol targeting multiple vulnerabilities of tumor cells in patients with advanced rectal cancer, particularly for patients with metastatic disease, without additional safety concerns. However, long term results are needed to draw firm conclusions.

 

Long-Term Survival Outcomes of Metabolically Supported Chemotherapy with Gemcitabine-Based or FOLFIRINOX Regimen Combined with Ketogenic Diet, Hyperthermia, and Hyperbaric Oxygen Therapy in Metastatic Pancreatic Cancer. Complement Med Res. 2020;27(1):31-39.

Abstract
Background: Despite introduction of new chemotherapeutic agents, outcomes of patients with metastatic pancreatic cancer are still poor. Metabolically supported chemotherapy (MSCT) is a novel approach targeting dysregulated energy mechanism of the tumor cell.

Objectives: This study aimed to examine the efficacy of metabolically supported administration of chemotherapy combined with ketogenic diet, hyperthermia, and hyperbaric oxygen therapy (HBOT) in patients with metastatic pancreatic cancer.

Method: This retrospective observational study included 25 patients with metastatic pancreatic ductal carcinoma (stage IV) who received MSCT (either gemcitabine-based or FOLFIRINOX regimen administered concomitantly with induced hypoglycemia) plus ketogenic diet, hyperthermia, and HBOT combination. Survival outcomes were evaluated.

Results: During the mean follow-up duration of 25.4 ± 19.3 months, median overall survival and median progression-free survival were 15.8 months (95% CI, 10.5–21.1) and 12.9 months (95% CI, 11.2–14.6), respectively. Age and gender did not have any effect on overall survival (p > 0.05 for all).

Conclusions: MSCT administered together with ketogenic diet, hyperthermia, and HBOT appears to be a viable option with the potential to improve survival outcomes in patients diagnosed with metastatic pancreatic cancer. Further research, particularly with larger comparative clinical trials, is warranted.

 

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. Int Jn Hyperthermia. 2019;36(1):446-455.

Abstract

Background: Previous evidence suggests that metabolically supported chemotherapy (MSCT), ketogenic diet, hyperthermia and hyperbaric oxygen therapy (HBOT) could all target vulnerabilities of cancer cells. This study aimed to evaluate the efficacy and the tolerability of this combination therapy in the treatment of stage IV non-small cell lung cancer (NSCLC).

Methods: Forty-four NSCLC patients with distant metastasis that received MSCT (administration of chemotherapy regimen following induced hypoglycemia) plus ketogenic diet, hyperthermia and HBOT combination were included in this retrospective study. Survival and treatment response rates as well as toxicities were evaluated.

Results: Overall response rate (ORR, complete response plus partial response) was 61.4%; whereas, 15.9% and 22.7% of patients had stable disease (SD) and progressive disease (PD), respectively. Mean overall survival (OS) and progression-free survival (PFS) was 42.9months (95% CI: 34.0–51.8) and 41.0months (95% CI: 31.1–50.9), respectively. A higher Eastern Cooperative Oncology Group (ECOG) performance status (ECOG 2) was associated with worse OS and PFS. Patients received chemotherapy cycles with acceptable toxicity and adverse events. No problems were encountered due to fasting, hypoglycemia, ketogenic diet, hyperthermia or hyperbaric oxygen therapy.

Conclusions: Findings of this study suggest that MSCT combined with other modalities targeting multiple pathways and cellular vulnerabilities may bring about remarkable improvements in survival outcomes and treatment response rates in metastatic NSCLC, without additional safety concerns. Large comparative studies are warranted to draw robust conclusions.

 

Efficacy of Metabolically Supported Chemotherapy Combined with Ketogenic Diet, Hyperthermia, and Hyperbaric Oxygen Therapy for Stage IV Triple-Negative Breast Cancer. Cureus. 2017 Jul 7;9(7).

Abstract

Triple-negative breast cancer (TNBC) is more aggressive and metastatic than other breast cancer types. Cytotoxic chemotherapy is presently the predominant systemic therapy for TNBC patients. This case report highlights the influence of metabolically supported chemotherapy (MSCT), ketogenic diet (KD), hyperthermia (HT), and hyperbaric oxygen therapy (HBOT) in an overweight 29-year-old woman with stage IV (T4N3M1) triple-negative invasive ductal carcinoma of the breast. The patient presented with an observable mass in her left breast detected during a physical examination in December 2015. Magnetic resonance imaging revealed a Breast Imaging Reporting and Data System Category 5 tumor and multiple lymphadenomegaly in the left axilla. A Tru-Cut biopsy led to the diagnosis of a triple-negative nuclear grade 2 invasive ductal carcinoma. The patient was admitted to ChemoThermia Oncology Center, Istanbul, Turkey in October 2016, and a whole body (18F)-fluorodeoxyglucose (FDG)-positron emission tomography-computed tomography (PET-CT) scan revealed a 77 mm x 55 mm primary tumor in her left breast, multiple left pectoral and axillary lymph nodes, multiple widespread liver masses, and an upper left nodular abdominal lesion. The patient received a treatment protocol consisting of MSCT, KD, HT, and HBOT. A follow-up whole body 18F-FDG PET-CT scan in February 2017 showed a complete therapeutic response with no evidence of abnormal FDG uptake. The patient continued to receive this treatment protocol and in April 2017 underwent a mastectomy, which revealed a complete pathological response consistent with the response indicated by her PET-CT imaging. This single case study presents evidence of a complete clinical, radiological, and pathological response following a six-month treatment period using a combination of MSCT and a novel metabolic therapy in a patient with stage IV TNBC.

 

Complete Response of Locally Advanced (stage III) Rectal Cancer to Metabolically Supported Chemoradiotherapy with Hyperthermia. Int J Cancer Res Mol Mech. 2016:2(1).

Abstract
Background: Locally advanced rectal cancer is defined as a rectal mass that cannot be resected without a high probability of leaving residual disease at the tumor site. While the standard treatment for locally advanced rectal cancer is chemoradiotherapy followed by surgery, this study reports a locally invasive rectal adenocarcinoma patient who achieved complete pathological and clinical remission after receiving a combination of metabolically supported chemotherapy (MSCT), radiotherapy (RT) and hyperthermia (HT).

Case presentation: An 81-year-old female underwent a rectosigmoidoscopy at a referring hospital following a complaint of bloody stools for a period of 20 days. The rectosigmoidoscopy revealed an ulcerated tumor beginning at the level of the anal sphincter. A pathological examination of biopsy material revealed moderately differentiated invasive adenocarcinoma and the patient received a diagnosis of stage III (T3N2Mx) low-lying rectal cancer. When further follow-up revealed colonic obstruction, the patient was recommended an abdominoperineal resection (APR) and was referred after refusing surgical treatment. The patient received a metabolically supported combination of oxaliplatin, 5-florouracil (5-FU) and calcium folinate (FOLFOX6) concomitant to RT and local HT and, ultimately, never underwent surgery. 27 months since her disease-free PET-CT scan, the patient remains with no sign of disease recurrence.

Conclusion: According to the findings of the present study, the non-surgical treatment and achievement of complete clinical and pathological remission of locally advanced rectal adenocarcinoma may be possible by means of a combination of MSCT, RT and HT.

 

Long-Term Outcomes of the Treatment of Unresectable (StageIII-IV) Ductal Pancreatic Adenocarcinoma Using Metabolically Supported Chemotherapy (MSCT): A Retrospective Study. J Pancreas (Online) 2016 Jan 08; 17(1):36-41.

Abstract
Background: Metabolically supported chemotherapy, is defined as the application of standard chemotherapy protocols concomitant to the administration of pharmacological doses of regular insulin and the development of hypoglycemia, and following fasting starting the previous day. This study aims to present the effects of metabolically supported chemotherapy on the overall survival of locally advanced and metastatic (stage III and stage IV, respectively), or simply unresectable pancreatic adenocarcinoma patients.

Material and methods: This study is a retrospective analysis of a prospectively maintained database of patients. It includes all patients that applied to our clinic between July 2012 and December 2014 that  were  diagnosed  with  unresectable (stage  III-IV)  pancreatic  adenocarcinoma.  The  demographic data  of  all  the  patients  as  well as  the  chemotherapy  regimen  received,  date of  treatment  initiation, date  of  disease remission,  mortality  and  overall  survival of  all  patients  were  analyzed using SPSS 20.0. Patient follow-up was performed by means of computed tomography and positron emission
tomography–computed tomography scans.

Results: 33 patients, 24(73%) males and 9(27%) females, were included in our study. The majority, 27(81%) patients, had metastatic disease at the time of diagnosis and were stage IV. While 11(33%) of the patients were treated using a gemcitabine-based protocol, 13(39%) received  FOLFIRINOX.  9(27%)  of  the  patients were  initially  treated  using  gemcitabine, but  began  receiving  FOLFIRINOX  following progression  as  second-line  chemotherapy. Statistical  analysis  revealed  a  median survival  of  19.5  months  and  a  1-year survival  rate  of  82.5%.  Presently, 18(54%) of the patients remain healthy and alive, free of disease progression with eastern cooperative oncology group performance statuses  ranging between  Grade  0  -1.  4(22%)  of  these patients  ultimately  underwent  radical  pancreatic surgery:  3(17%)  having  undergone pancreaticoduodenectomies (Whipple procedures) and 1(5%) having undergone a distal pancreatectomy.

Conclusion: This study demonstrates that a metabolically supported form of applying standard chemotherapy regimens may enhance the overall survival rates of unresectable (stage III-IV) pancreatic adenocarcinoma patients.