Effects of Short-term Fasting on Tolerance to Chemotherapy

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine the effect of short-term fasting on tolerance to adjuvant chemotherapy in breast cancer patients

Detailed Description
-----------------
Evidence from experimental animals provides strong support for the concept that caloric restriction (CR) increases resistance to multiple forms of stress. CR decreases plasma levels of growth factors, e.g. insulin-like growth factor-I (IGF-I), thereby diverting energy from growth to maintenance. Accordingly, the currently available information suggests that short-term fasting protects normal cells against the perils of (high dose) chemotherapy. In contrast, cancer cells are not (or less) protected as a result of their self-sufficiency in growth signals. This phenomenon is termed Differential Stress Resistance (DSR). DSR reduces the severity of side-effects caused by the toxicity of chemotherapy, without interfering with its effect on reduction of tumour volume or tumour markers. A recent report, sketching a case series of 10 cancer patients, suggests that short term fasting protects against the side effects of chemotherapy in humans. Indeed, the majority of patients preferred fasting over feeding in preparation of their therapy. This study aims to further evaluate the impact of fasting on tolerance to chemotherapy in humans.

Official Title
-----------------
Effects of Short-term Fasting on Tolerance to Adjuvant Chemotherapy in Breast Cancer Patients

Conditions
-----------------
Breast Cancer

Intervention / Treatment
-----------------
* Other: Short-term fasting
* Other: Healthy nutrition


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Female breast cancer patients, receiving adjuvant TAC-chemotherapy Age ≥ 18 years old WHO performance status 0-2 Adequate bone marrow function: white blood cells (WBCs) ≥ 3.0 x 109/l, neutrophils ≥ 1.5 x 109/l, platelets ≥ 100 x 109/l Adequate liver function: bilirubin ≤ 1.5 x upper limit of normal (UNL) range, ALAT and/or ASAT ≤ 2.5 x UNL, Alkaline Phosphatase ≤5 x UNL Adequate renal function: the calculated creatinine clearance should be ≥ 50 mL/min Survival expectation > 3 months Patients must be accessible for treatment and follow-up Written informed consent according to the local Ethics Committee requirements Exclusion Criteria: Serious other diseases such as recent myocardial infarction, clinical signs of cardiac failure or clinically significant arrhythmias Diabetes Mellitus body mass index (BMI) < 19 kg/m2 Pregnancy or lactating Medical or psychological condition which in the opinion of the investigator would not permit the patient to complete the study or sign meaningful informed consent

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Short-term fasting<br>short term fasting (i.e. 24 hours before and 24 hours after administration of chemotherapy) in 20 breast cancer patients | Other: Short-term fasting<br>* Short-term fasting, i.e. 24 hours before and 24 hours after administration of chemotherapy<br>|
| Placebo Comparator: Healthy nutrition<br>20 breast cancer patients eat according to the current guidelines for healthy nutrition as from 24 hours before until 24 hours after the beginning of administration of chemotherapy. | Other: Healthy nutrition<br>* Eating according to the current guidelines for healthy nutrition as from 24 hours before until 24 hours after the beginning of administration of chemotherapy. Dietary instructions will be given by a dietician and actual food intake will be recorded in a journal.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| chemotherapy-induced neutropenia | Neutrophil count after 6 cycles of chemotherapy (6x 21 days) | approximately 126 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| chemotherapy-induced DNA damage in leukocytes | chemotherapy-induced DNA damage in leukocytes will be determined after each cycle of chemotherapy (i.e. every 21 days) | 21 days | 
| perceived side effects of chemotherapy | To determine the effect of short-term fasting on perceived side effects after each cycle of chemotherapy (i.e. every 21 days) | 21 days | 
| effect of short-term fasting on the body's inflammatory response to chemotherapy | To determine the effect of short-term fasting on the body's inflammatory response to chemotherapy, inflammation parameters will be measured after each cycle of chemotherapy | 21 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
short-term fasting, adjuvant chemotherapy, toxicity, side-effects