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INTERNATIONAL JOURNAL OF HYPERTHERMIA
2019, VOL. 36, NO. 1, 445–454

https://doi.org/10.1080/02656736.2019.1589584
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
Mehmet Salih Iyikesicia,b
a
Department of Medical Oncology, School of Medicine, Altinbas University, Istanbul, Turkey; bChemoThermia Oncology Center,
Istanbul, Turkey
ABSTRACT ARTICLE HISTORY

Background: Previous evidence suggests that metabolically supported chemotherapy (MSCT), keto- Received 10 September 2018
genic diet, hyperthermia and hyperbaric oxygen therapy (HBOT) could all target vulnerabilities of can- Revised 22 February 2019
cer cells. This study aimed to evaluate the efficacy and the tolerability of this combination therapy in Accepted 27 February 2019
the treatment of stage IV non-small cell lung cancer (NSCLC).
Methods: Forty-four NSCLC patients with distant metastasis that received MSCT (administration of KEYWORDS
chemotherapy regimen following induced hypoglycemia) plus ketogenic diet, hyperthermia and HBOT Non-small cell lung cancer
combination were included in this retrospective study. Survival and treatment response rates as well (NSCLC); metabolically
as toxicities were evaluated. supported chemotherapy
Results: Overall response rate (ORR, complete response plus partial response) was 61.4%; whereas, (MSCT); ketogenic diet;
15.9% and 22.7% of patients had stable disease (SD) and progressive disease (PD), respectively. Mean hyperbaric oxygen therapy
overall survival (OS) and progression-free survival (PFS) was 42.9 months (95% CI: 34.0–51.8) and (HBOT); hyperthermia;
41.0 months (95% CI: 31.1–50.9), respectively. A higher Eastern Cooperative Oncology Group (ECOG) warburg hypothesis
performance status (ECOG 2) was associated with worse OS and PFS. Patients received chemother-
apy 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 mul-
tiple pathways and cellular vulnerabilities may bring about remarkable improvements in survival out-
comes and treatment response rates in metastatic NSCLC, without additional safety concerns. Large
comparative studies are warranted to draw robust conclusions.
Introduction patients with advanced NSCLC [7,8]. Although several regi-

mens have demonstrated very similar efficacy in large phase
Lung cancer is the most common cancer worldwide with
III trials, at present, carboplatin combined with paclitaxel is a
1.8 million new patients diagnosed globally in 2012; and it
commonly administered combination regimen, due to more
is the leading cause of cancer-related mortality causing an
favorable toxicity profile of carboplatin allowing administra-
estimated 1.6 million deaths in the same year [1,2]. Lung tion on an outpatient basis [9]. In addition, the use of
cancer is categorized into two broad classes: small cell lung immunotherapy for advanced NSCLC is newly immerging in
carcinoma (SCLC) and non-small cell lung carcinoma (NSCLC). the field and has been started to be integrated into the first
NSCLC accounts for about 85% of all malignancies originat- line treatment [10–14].
ing from the lungs [3,4]. Despite advances in monitoring and Over the past decade, several trials have been conducted
diagnostic imaging techniques, nearly 40% of all NSCLC to evaluate different schedules of carboplatin/paclitaxel
patients are diagnosed at advanced stages with distant administration with the aim of enhancing efficacy and toler-
metastasis [4,5]. ability [7,15–18]; however, trials focusing on patients with
In patients diagnosed with stage I, II or III NSCLC, treat- impaired performance status and related comorbidities are
ment is generally with curative intent and usually includes a lacking [19].
combination of surgery, radiation therapy (RT) and chemo- Unlike normally differentiated cells, cancer cells exhibit a
therapy. However, in the case of stage IV patients in whom dysregulated energy metabolism. Similar to normal develop-
toxicity is a major concern, optimal management is not well- ing cells and proliferating cells, they exhibit an increased glu-
defined [6,7]. Currently, cytotoxic chemotherapy with a plat- cose uptake leading to the lactate production, even in the
inum-based doublet is the first-line treatment modality for presence of oxygen [20]. This phenomenon is called the
CONTACT Mehmet Salih Iyikesici [email protected] Altinbas Universitesi Tip Fakultesi, Tibbi Onkoloji Bolumu, Bahcelievler E-5 Karayolu Kultur Sokak
No:1 Bahcelievler, Istanbul 34180, Turkey
ß 2019 The Author(s). Published with license by Taylor & Francis Group, LLC
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use,
distribution, and reproduction in any medium, provided the original work is properly cited.

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INTERNATIONAL JOURNAL OF HYPERTHERMIA

2019, VOL. 36, NO. 1, 445–454

Feasibility study of metabolically supported chemotherapy with weekly

ABSTRACT ARTICLE HISTORY

Introduction patients with advanced NSCLC [7,8]. Although several regi-

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