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

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.

Addressing the controversial role of ketogenic diets in cancer treatment

“…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]. Finally, a randomized controlled trial in breast cancer patients receiving neoadjuvant chemotherapy found that a KD resulted in significantly longer overall survival compared to a control diet over a follow-up period of 30 months [22].…”

Evre II-IV rektum kanserinde metabolik destekli kemoterapinin ketojenik diyet, hipertermi ve hiperbarik oksijen tedavisi ile kombinasyonunun ön sonuçları

“…Clinical evidence on the potential benefit of MSCT comes from clinical studies with pancreatic cancer patients and non-small cell lung cancer patients as well as from two case reports. In a recent study with stage IV ductal pancreatic adenocarcinoma patients, metabolically supported administration of chemotherapy resulted in promising survival outcomes with a reported median survival of 15.8 months [9]. Another recent study reported encouraging results in stage IV non-small cell lung cancer with a mean 42.9 months overall survival rate [10].…”

“…All eligible patients were advised to adapt a ketogenic diet during the study period and they were asked to fast for 12 hours before each chemotherapy session. In addition to the premedication with 45.5 mg pheniramine maleate and 0.25 mg palonosetron HCl, each patient received regular insulin (Humulin® R) in doses ranging between 5-20 IU prior to chemotherapy administration in order to achieve a state of mild hypoglycemia with blood glucose levels around 50-60 mg/dl for normoglycemic patients and in accordance with MSCT protocols [7][8][9][10]. Following each MSCT administration, patients received a 60-minute session of hyperthermia and a 60-minute session of HBOT.…”

“…Metabolically Supported Chemotherapy (MSCT) is a novel chemotherapy application strategy targeting metabolic vulnerabilities of cancer cells [7][8][9][10]. Cancer cells have a dysregulated energy metabolism almost evident in all tumor types [11], which was first recognized by Otto Warburg, in 1924 [12,13].…”

“…Adopting a ketogenic diet further decreases circulating glucose levels. A high-fat, carbohydrate-restricted ketogenic diet has been shown to slow the progression of cancer [8,9,17,18].…”