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INTRODUCTION
Chemotherapy can extend survival in patients diagnosed
with a wide range of malignancies. However, side
effects caused by toxicity to normal cells and tissues limit
Researchpaper
chemotherapy dose density and intensity, which may
compromise efficacy. For instance, the cardiotoxicity
and nephrotoxicity associated with the widely
prescribed anti-cancer drugs, doxorubicin and cisplatin
respectively limit their full therapeutic potential [1, 4].
www.impactaging.com AGING, December 2009 Vol.1 No 12
FastingandCancerTreatmentinHumans:ACaseseriesreport
FernandoM.Safdie1,6,TanyaDorff2,3,6,DavidQuinn2,3,LuigiFontana4,MinWei1,Changhan
Lee1,PinchasCohen5,andValterD.Longo1
1AndrusGerontologyCenterandDepartmentofBiologicalSciences,UniversityofSouthernCalifornia,Los
Angeles,CA90089,USA
2UniversityofSouthernCaliforniaKeckSchoolofMedicine,LosAngeles,CA90089,USA
3UniversityofSouthernCaliforniaNorrisCancerCenter,LosAngeles,CA90089,USA
4DivisionofGeriatricsandNutritionalScience.CenterforHumanNutrition,WashingtonUniversitySchoolof
Medicine.DivisionofNutritionandAging.IstitutoSuperiorediSanità,Rome,Italy
5UCLADept.ofPediatricEndocrinology,LosAngeles,CA90095,USA
6Theseauthorscontributedequallytothiswork
Runningtitle:FastingandCancerTreatment
Keywords:fasting,Cancer,Chemotherapy,Toxicity,Side‐effect,IGF‐I
Correspondence:ValterD.Longo,PhD,AndrusGerontologyCenterandDepartmentofBiologicalSciences,Universityof
SouthernCalifornia,3715McClintockAvenue,LosAngeles,CA90089‐0191
Received:12/22/09;accepted:12/30/09;publishedonline:12/31/09
E‐mail:vlongo@usc.edu
Copyright:©Safdieetal.Thisisanopen‐accessarticledistributedunderthetermsoftheCreativeCommonsAttribution
License,whichpermitsunrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalauthorandsource
arecredited
Abstract:Short‐termfasting(48hours)wasshowntobeeffectiveinprotectingnormalcellsandmicebutnotcancercells
againsthighdosechemotherapy,termedDifferentialStressResistance(DSR),butthefeasibilityandeffectoffastingin
cancerpatientsundergoingchemotherapyisunknown.Herewedescribe10casesinwhichpatientsdiagnosedwitha
varietyofmalignancieshadvoluntarilyfastedpriorto(48‐140hours)and/orfollowing(5‐56hours)chemotherapy.Noneof
thesepatients,whoreceivedanaverageof4cyclesofvariouschemotherapydrugsincombinationwithfasting,reported
significantsideeffectscausedbythefastingitselfotherthanhungerandlightheadedness.Chemotherapyassociated
toxicitywasgradedaccordingtotheCommonTerminologyCriteriaforAdverseEvents(CTCAE)oftheNationalCancer
Institute(NCI).Thesixpatientswhounderwentchemotherapywithorwithoutfastingreportedareductioninfatigue,
weakness,andgastrointestinalsideeffectswhilefasting.Inthosepatientswhosecancerprogressioncouldbeassessed,
fastingdidnotpreventthechemotherapy‐inducedreductionoftumorvolumeortumormarkers.Althoughthe10cases
presentedheresuggestthatfastingincombinationwithchemotherapyisfeasible,safe,andhasthepotentialto
amelioratesideeffectscausedbychemotherapies,theyarenotmeanttoestablishpracticeguidelinesforpatients
undergoingchemotherapy.Onlycontrolled‐randomizedclinicaltrialswilldeterminetheeffectoffastingonclinical
outcomesincludingqualityoflifeandtherapeuticindex.
www.impactaging.com 1AGING,December2009,Vol.1No.12
Thus, reduction of undesired toxicity by selective
protection of normal cells without compromising the
killing of malignant cells represents a promising
strategy to enhance cancer treatment.
Calorie restriction (CR) is an effective and reproducible
intervention for increasing life span, reducing oxidative
damage, enhancing stress resistance and delaying/preven-
ting aging and age-associated diseases such as cancer in
various species, including mammals (mice, rats, and non-
human primates) [5-8]. Recently, a fasting-based
intervention capable of differentially protecting normal
and cancer cells against high-dose chemotherapy in cell
culture and in neuroblastoma-bearing mice was reported
[9]. In the neuroblastoma xenograft model, mice were
allowed to consume only water for 48 hours prior to
etoposide treatment. Whereas high dose etoposide led to
50% lethality in ad libitum fed mice, fasting protected
against the chemotoxicity without compromising the
killing of neuroblastoma cells [9].
Table1.Toxicitysideeffectsurvey
Fatigue ** 0 1 2 3
4 Being extreme Fatigue
Weakness *** 0 1 2 3 4
4 Being Extreme Weakness
Hair Loss 0 1 2 3 4
4 Being Maximum Hair Loss
36.5°C
/97.7°
37.0°C
/98.6°
37.5°C
/99.5°
38.0°C
/100.4°
38.5°C
/101.3°
39.0°C
/102.2°
39.5°C
/103.1°
40.0°C
/104°
40.5°C
/104.9°
41.0°C
/105.8°
Body Temperature
Head Aches 0 1 2 3 4
4 Being the Worst Headache
Gastrointestinal Side Effects
Appetite 0 1 2 3 4
4 Being Strong Appetite
Nausea 0 1 2 3 4
4 Being Unbearable Nausea
Mild Moderate Severe
0
Vomiting < 2 times/Day 3-5 times/ Day >5 times/Day
Mild Moderate Severe
0
Diarrhea < 2 times/Day 3-5 times/ Day >5 times/Day
Abdominal Cramps
0 1 2 3 4
4 Being Extreme Abdominal
Cramps
Mouth Sores 0 1 2 3 4
4 Being Extremely Painful
Dry Mouth 0 1 2 3 4
4 Extreme Dryness
CNS AND PNS Side Effects
Short memory impairment 0
www.impactaging.com 2AGING,December2009,Vol.1No.12
4
4 Being High Impairment
Numbness 0 1 2 3 4
4 Being Maximum
Tingling 0 1 2 3 4
4 Being Maximum
Neuropathy-motor 0 1 2 3 4
4 Being = Paralysis
*Grade:0nosymptom,1to4frommild,moderate,severeandlifethreatening(requiresmedicalassistance)
**Fatigue:unusualtirednesswhichisnotrelievedbyeitheragoodnightofsleeporrest.
***Weakness:lackofstrength,vigororfirmness
Previous human studies have shown that alternate day
dietary restriction and short-term fasting (5 days) are
well tolerated and safe [10-12]. In fact, children ranging
from 6 months to 15 years of age were able to complete
14 to 40 hours of fasting in a clinical study carried out
at the Children’s hospital of Philadelphia [13].
Furthermore, alternate day calorie restriction caused
clinical improvements and reduced markers of
inflammation and oxidative stress in obese asthmatic
patients [12, 14].
Here, we report 10 cases of patients diagnosed with
various types of cancer, who have voluntarily fasted
prior to and following chemotherapy. The results
presented here, which are based on self-assessed health
outcomes (Table 1) and laboratory reports, suggest that
fasting is safe and raise the possibility that it can reduce
chemotherapy-associated side effects. However, only a
randomized controlled clinical trial can establish its
efficacy.
RESULTS
Ten cancer patients receiving chemotherapy, 7 females
and 3 males with a median age of 61 years (range 44-78
yrs), are presented in this case series report. Four suffered
from breast cancer, two from prostate cancer, and one
each from ovarian, uterine, non small cell carcinoma of
the lung, and esophageal adenocarcinoma. All patients
voluntarily fasted for a total of 48 to 140 hours prior to
and/or 5 to 56 hours following chemotherapy
administered by their treating oncologists (Tables 2, 3).
Figure1.Self‐reportedside‐effectsafterchemotherapywithorwithoutfasting.Data
representaverageofCTCAEgradefrommatchingfastingandnon‐fastingcycles(AdLib).6patients
receivedeitherchemotherapy‐aloneorchemo‐fastingtreatments.Self‐reportedsideeffectsfrom
theclosesttwocycleswerecomparedoneanother.Statisticanalysiswasperformedonlyfrom
matchingcycles.Datapresentedasstandarderrorofthemean(SEM).Pvaluewascalculatedwith
unpaired,twotailttest.(*,P<0.05).
www.impactaging.com 3AGING,December2009,Vol.1No.12
Table2.Additionaldatafrompatients,includingschemeofchemotherapycycles,fastingregimens
andtumorresponse
Cycle
#
Fast
(hours)
Chemotherapy Tumor Response
Case 1 1 140 pre
40 post
Docetaxel 75mg/m2 +
Cyclophosphamide 600mg/m2 n/a
4 120 pre
24 post
Docetaxel 75mg/m2 +
Cyclophosphamide 600mg/m2 n/a
Case 2 4 72 pre
51 post
Docetaxel 64.6mg/m2 + carboplatin 485mg
+ 5FU 2415.7 mg/m2 ---
5 48 pre
56 post
Docetaxel 79 mg/m2 + carboplatin 470mg
+ 5FU 2415.7 mg/m2 Stable disease on CT/PET
6 48 pre
56 post
Docetaxel 79 mg/m2 + carboplatin 470mg
+ 5FU 2415.7 mg/m2
Improvement on CT/PET.
Refer to text.
7 48 pre
56 post
Docetaxel 79 mg/m2 + carboplatin 470mg
+ 5FU 2415.7 mg/m2 ---
8 48 pre
56 post
Docetaxel 79 mg/m2 + carboplatin 470mg
+ 5FU 2415.7 mg/m2
Progression of Disease on
CT/PET
Case 3 5- 12 60-66 pre
24 post
Docetaxel 75 mg/m2 See PSA Graph
Case 4 6 48 pre
24 post
Docetaxel 75mg/m2 + carboplatin 540mg Stable disease CT/PET refer to
text
Case 5 2 36 pre Carboplatin 480 mg + Paclitaxel 280 mg ---
3-4 60 pre Carboplatin 480 mg + Paclitaxel 280 mg 87% decline in CA 125,
Reduction in lymph nodes on
CT
5-6 60 pre
24post
Carboplatin 480 mg + Paclitaxel 280 mg
Case 6 3 62 pre
24post
Gemcitabine 720 mg/m2 (day1) +
GMZ 720 mg/m2 Docetaxel 80 mg/m2 (Day8) ---
4 62 pre
24post
Gemcitabine 720 mg/m2 (day1) +
GMZ 720 mg/m2 Docetaxel 80 mg/m2 (Day8) ---
5-6 62 pre
24post
Gemcitabine 900 mg/m2 (day1) +
GMZ 900 mg/m2 Docetaxel 100 mg/m2 (Day8)
Stable disease on PET scan,
No new METS.
Case 7 1 65 pre
8 post
Docetaxel 60 mg/m2 See PSA Graph
2-8 65 pre
25post*^
Docetaxel 75 mg/m2 See PSA Graph
Case 8 1-4 64 pre
24 post**
Docetaxel 75 mg/m2 + Cyclophosphamide 600
mg/m2 n/a
Case 9 1 48 pre Doxorubicin 110 mg +
Cyclophosphamide 1100 mg n/a
2-4 61 pre
4 post
Doxorubicin 110 mg +
Cyclophosphamide 1100 mg n/a
Case 10 1 60 pre Docetaxel 75 mg/m2 + Carboplatin 400mg n/a
2 48 pre Docetaxel 75 mg/m2 + carboplatin 400mg n/a
3 40 pre
24post
Docetaxel 75 mg/m2 + carboplatin 400mg n/a
4 48 pre
24post
Docetaxel 75 mg/m2 + carboplatin 400mg n/a
5 36 pre
24post
Docetaxel 75 mg/m2 + carboplatin 400mg n/a
6 20 pre
20post
Docetaxel 75 mg/m2 + carboplatin 400mg n/a
*alsoutilizedlowglycemicdietfor24hourspriortofast.
**alsoutilizedliquiddietfor24hoursafterfast.
n/a=notapplicable,duetochemotherapybeingadministeredintheadjuvantsetting.
www.impactaging.com 4AGING,December2009,Vol.1No.12
Case 1
This is a 51-year-old Caucasian woman diagnosed with
stage IIA breast cancer receiving adjuvant chemo-
therapy consisting of docetaxel (TAX) and cyclo-
phosphamide (CTX). She fasted prior to her first
chemotherapy administration. The fasting regimen
consisted of a complete caloric deprivation for 140
hours prior and 40 hours after chemotherapy (180 hours
total), during which she consumed only water and
vitamins. The patient completed this prolonged fasting
without major inconvenience and lost 7 pounds, which
were recovered by the end of the treatment (Figure 2H).
After the fasting-chemotherapy cycle, the patient
experienced mild fatigue, dry mouth and hiccups
(Figure 2I); nevertheless she was able to carry out her
daily activities (working up to 12 hours a day). By
contrast, in the subsequent second and third treatment,
she received chemotherapy accompanied by a regular
Table3.Additionaldemographicalandclinicalinformationofpatients
Gender Age Primary Neoplasia Stage at Diagnosis
Case 1 Female 51 Breast IIA
Case 2 Male 68 Esophagus IVB
Case 3 Male 74 Prostate II
Case 4 Female 61 Lung (NSCLC) IV
Case 5 Female 74 Uterus IV
Case 6 Female 44 Ovary IA
Case 7 Male 66 Prostate IV/DI
Case 8 Female 51 Breast IIA
Case 9 Female 48 Breast IIA
Case 10 Female 78 Breast IIA
diet and complained of moderate to severe fatigue,
weakness, nausea, abdominal cramps and diarrhea
(Figure 2I). This time the side effects forced her to
withdraw from her regular work schedule. For the forth
cycle, she opted to fast again, although with a different
regimen which consisted of fasting 120 hours prior to
and 24 hours post chemotherapy. Notably, her self-
reported side effects were lower despite the expected
cumulative toxicity from previous cycles. Total white
blood cell (WBC) and absolute neutrophil counts (ANC)
were slightly better at nadir when chemotherapy was
preceded by fasting (Figure 2A, C; Table S1).
Furthermore, platelets level decreased by 7-19% during
cycles 2 and 3 (ad libitum diet) but did not drop during
the first and forthcycles (fasting), (Figure 2D). After the
forthchemotherapy cycle combined with 144-hour fast
her ANC, WBC, and platelet counts reached their
highest level since the start of chemotherapy 80 days
earlier (Figure 2A, C and D).
www.impactaging.com 5AGING,December2009,Vol.1No.12
Case 2
This is a 68-year-old Caucasian male diagnosed in
February 2008 with esophageal adenocarcinoma
metastasic to the left adrenal gland. The initial treatment
consisted of 5-fluorouracil (5-FU) combined with
cisplatin (CDDP) concurrent with radiation for the first
two cycles. Throughout these first two cycles, the patient
Figure2.Laboratoryvaluesofbloodcellcountsforcase1.(A)Neutrophils;(B)Lymphocytes;(C)Whitebloodcells,WBC;(D)Platelets;
(E)Redbloodcells,RBC(F)Hemoglobin,Hgb;(G)Hematocrit,Hct;(H)Bodyweight.Filledtriangleindicatesdayofchemotherapy;open
squareindicatesfasting.Normalrangesoflaboratoryvaluesareindicatebydashlines;(I)Self‐reportedside‐effectsafterchemotherapyfor
case1.Datarepresenttheaverageof2cyclesofchemo‐alonevstheaverageof2cyclesofchemo‐fastingtreatments.
experienced multiple side effects including severe
weakness, fatigue, mucositis, vomits and grade 2-3
peripheral neuropathy (Figure 3). During the third
cycle, 5-FU administration was interrupted due to
severe nausea and refractory vomiting (Figure 3). In
spite of the aggressive approach with chemotherapy and
radiation, his disease progressed with new metastases to
the right adrenal gland, lung nodules, left sacrum, and
www.impactaging.com 6AGING,December2009,Vol.1No.12
coracoid process documented by computed tomography
- positron emission tomography (CT-PET) performed in
August 2008. These prompted a change in his
chemotherapy regimen for the fourth cycle to
carboplatin (CBDCA) in combination with TAX and 5-
FU (96 hour infusion) (Table 2). During the fourth
cycle, the patient incorporated a 72-hour fast prior to
chemotherapy and continued the fast for 51 hours
afterward, consuming only water. The rationale for the
51 hour post-chemotherapy fasting was to cover the
period of continuous infusion of 5-FU. The patient lost
approximately 7 pounds, of which 4 were regained
during the first few days after resuming ad libitum diet
(data not shown). Although a combination of three
chemotherapeutic agents were used during this cycle,
self-reported side effects were consistently less severe
compared to cycles in which calories were consumed ad
lib (Figure 3). Prior to his fifth cycle the patient opted to
fast again. Instead of receiving the 5-FU infusion for 96
hours, as he did previously, the same dose of the drug
was administered within 48 hours, and the fasting
regimen was also modified to 48 hours prior and 56
hours post chemotherapy delivery. Self-reported side
effects were again less severe than those in association
with ad libitum diet and the restaging CT-PET scan
indicated objective tumor response, with decreased
standard uptake values (SUV) in the esophageal mass,
the adrenal gland metastases, and the lung nodule. From
the sixth to eight cycle, the patient fasted prior to and
following chemotherapy treatments (Table 2). Fasting
was well tolerated in all cycles and chemotherapy-
dependent side effects were reduced except for mild
diarrhea and abdominal cramps that were developed
during the seventh cycle (Figure 3). Ultimately, the
patient’s disease progressed and the patient died in
February 2009.
Figure3.Sel
f
‐reportedside‐effectsafterchemotherapyforcase2.Datarepresentthe
averageof3cyclesofchemo‐alonevstheaverageof5cyclesofchemo‐fastingtreatments.
www.impactaging.com 7AGING,December2009,Vol.1No.12
Case 3
This is a 74-year-old Caucasian man who was
diagnosed in July 2000 with stage II prostate adeno-
carcinoma, Gleason score 7 and baseline PSA level of
5.8 ng/ml. He achieved an undetectable PSA nadir after
radical prostatectomy performed in September of 2000,
but experienced biochemical recurrence in January 2003
when PSA rose to 1.4 ng/ml. Leuprolide acetate
together with bicalutamide and finasteride were
prescribed. However, administration of these drugs had
to be suspended in April 2004 due to severe side effects
related to testosterone deprivation. Additional therapies
including triptorelin pamoate, nilutamide, thalidomide,
CTX and ketoconazole failed to control the disease. In
2007 the patient’s PSA level reached 9 ng/ml and new
metastases were detected on bone scan. Despite that
TAX at 25mg/m2 was administered on weekly basis, the
PSA level continued to increase, reaching 40.6 ng/ml
(data not shown). Bevacizumab was added to the
treatment and only then did the PSA drop significantly
(data not shown). Throughout the cycles with
chemotherapy the patient experienced significant side
effects including fatigue, weakness, metallic taste, dizzi-
Figure4.Laboratoryvaluesofbloodcellcountsforcase3.(A)Neutrophils;(B)Lymphocytes;(C)Whitebloodcells,WBC;(D)
Platelets;(E)Redbloodcells,RBC(F)Hemoglobin,Hgb;(G)Hematocrit,Hct;(H)Prostatespecificantigen(PSA)level.Thepatientwas
enrolledinabirateroneacetate(CYP17inhibitor)trialfor90daysindicatedbyverticaldashlines.ThepatientalsoreceivedG‐CSF
(Neulasta)onthedayofchemotherapyexceptduringthetreatmentwithabirateroneacetate.Filledtriangleindicatesdayof
chemotherapy;opensquareindicatesfasting,arrowindicatestestosteroneapplication(cream1%).Normalrangesoflaboratoryvalues
areindicatedbyhorizontaldashlines;(I)Self‐reportedside‐effectsafterchemotherapyforcase3.Datarepresenttheaverageof5cycles
ofchemo‐alonevstheaverageof7cyclesofchemo‐fastingtreatments.
www.impactaging.com 8AGING,December2009,Vol.1No.12
ness, forgetfulness, short-term memory impairment and
peripheral neuropathy (Figure 4I). After discontinuing
the chemotherapy, his PSA rose rapidly. TAX was
resumed at 75mg/m2 every 21 days, and was
complemented with granulocytic colony stimulating
factor (G-CSF). Once again the patient suffered
significant side effects (Figure 4I). In June 2008,
chemotherapy was halted. The patient was enrolled in a
phase III clinical trial with abiraterone acetate, a drug that
can selectively block CYP17, a microsomal enzyme that
catalyzes a series of reactions critical to nongonadal
androgen biosynthesis [15]. During the trial, the patient’s
PSA levels increased to 20.9ng/dl (Figure 4H),
prompting resumption of chemotherapy and G-CSF. This
time the patient opted to fast prior to chemotherapy. His
fasting schedule consisted of 60 hours prior to and 24
post drug administration (Table 2). Upon restarting
chemotherapy with fasting the PSA level dropped, and
notably, the patient reported considerably lower side
effects than in previous cycles in which he consumed
calories ad-lib (Figure 4I). He also experienced reduced
myelosuppression (Figure 4A-G). During the last three
cycles, in addition to fasting, the patient applied
testosterone (cream, 1%) for five days prior to
chemotherapy. As a consequence the PSA level along
with the testosterone level increased dramatically.
Nonetheless, 3 cycles of chemotherapy combined with
fasting reduced PSA from 34.2 to 6.43 ng/ml (Figure
4H). These results imply that the cytotoxic activity of
TAX to cancer cells was not blocked by fasting.
Figure5.Laboratoryvaluesofbloodcellcountsforcase4.(A)Neutrophils;(B)Lymphocytes;(C)Whitebloodcells,WBC;(D)
Platelets;(E)Redbloodcells,RBC(F)Hemoglobin,Hgb;(G)Hematocrit,Hct;Filledtriangleindicatesdayofchemotherapy;opensquare
indicatesfasting.Normalrangesoflaboratoryvaluesareindicatedbydashlines;(H)Self‐reportedside‐effectsafterchemotherapyfor
case4.Datarepresenttheaverageof5cyclesofchemo‐alonevs1cycleofchemo‐fastingtreatment.
www.impactaging.com 9AGING,December2009,Vol.1No.12
Case 4
This is a 61-year-old Caucasian female who was
diagnosed in June 2008 with poorly differentiated non-
small cell lung carcinoma (NSCLC). A staging PET scan
documented a hypermetabolic lung mass, multiple
mediastinal and left perihilar lymph nodes, and
widespread metastatic disease to the bones, liver, spleen,
and pancreas. The initial treatment commenced with the
administration of TAX 75 mg/m2 and CBDCA 540mg
every 21 days. Although she was on a regular diet, during
the first 5 cycles she lost an average of 4 pounds after
each treatment, most likely due to chemotherapy-induced
anorexia. The patient reported that she did return to her
original weight but only after three weeks of the drug
administration, just before a new cycle. Additional side
effects included severe muscle spasms, peripheral
neuropathy, significant fatigue, mucositis, easy bruising
and bowel discomfort (Figure 5H). During the sixth
cycle, which consisted of the same drugs and dosages, the
patient fasted for 48-hours-prior and 24-hours-post
chemotherapy. She lost approximately 6 pounds during
the fasting period, which she recovered within 10 days
(data not shown). Besides mild fatigue and weakness, the
patient did not complain of any other side effect which
was experienced during the five previous cycles (Figure
5H). Cumulative side effects such as peripheral
neuropathy, hair loss and cognitive impairment were not
reversed. By contrast self-reported acute toxic side
effects were consistently reduced when chemotherapy
was administered in association with fasting (Figure 5H).
In the sixth and last cycle, the patient reported that her
strength returned more quickly after the chemotherapy so
that she was able to walk 3 miles three days after the drug
administration, whereas in previous cycles (ad libitum
diet) she had experienced severe weakness and fatigue
which limited any physical activity. No significant
differences were observed in the patient’s blood analysis
(Figure 5A-G). The last PET scan performed on February
2009 showed stable disease in the main mass (lungs) and
decreased uptake in the spleen and liver when compared
to her baseline study.
Case 5
This is a 74 year-old woman diagnosed in 2008 with
stage IV uterine papillary serous carcinoma. Surgery
(Total Abdominal Hysterectomy-Bilateral Salpingo-
Oopherectomy, TAH-BSO, with lymph node
dissection) followed by adjuvant chemotherapy were
recommended. Due to significant enlargement of the
right ureter, a right nephrectomy was also performed.
Post-operatively, six cycles of CBDCA (480mg) and
paclitaxel (280mg) were administered every 21-days.
During the first treatment the patient maintained her
regular diet and experienced fatigue, weakness, hair
loss, headache and gastrointestinal discomfort (Figure
6). By contrast, during cycles 2-6, the patient fasted
before and after chemotherapy, and reported a reduction
in the severity of chemotherapy-associated side effects
(Table 2; Figure 6). Fasting did not appear to interfere
with chemotherapy efficacy, as indicated by the 87%
reduction in the tumor marker CA-125 after the forth
cycle (data not shown).
Figure6.Self‐reportedside‐effectsafterchemotherapyforcase5.Datarepresent1cycle
ofchemotherapy‐alone(firstcycle)vstheaverageof5cyclesofchemo‐fastingtreatments.
www.impactaging.com 10AGING,December2009,Vol.1No.12
Case 6
This is a 44-year-old Caucasian female diagnosed with a
right ovarian mass (10x12 cm.) in July 2007. Surgery
(TAH-BSO) revealed stage IA carcinosarcoma of the
ovary with no lymph node involvement. Adjuvant
treatment consisted of six cycles of ifosfamide and
CDDP, administered from July to November of 2007.
She remained free of disease until an MRI revealed
multiple new pulmonary nodules in August 2008. Conse-
quently chemotherapy with taxol, carboplatin and
bevacizumab was initiated. By November, however, a
CT scan showed progression of the cancer. Treatment
was changed to gemcitabine plus TAX complemented
with G-CSF (Neulasta) (Table 2 and Table S2). After the
first dose of gemcitabine (900 mg/m2), the patient
experienced prolonged neutropenia (Figure 7A) and
thrombocytopenia (Figure 7D), which forced a delay of
day 8 dosing. During the second cycle the patient
received a reduced dose of gemcitabine (720 mg/m2), but
Figure7.Laboratoryvaluesofbloodcellcountsforcase6.(A)Neutrophils;(B)Lymphocytes;(C)Whitebloodcells,WBC;(D)
Platelets;(E)Redbloodcells,RBC(F)Hemoglobin,Hgb;(G)Hematocrit,Hct;Filledtriangleindicatesdayofchemotherapy;opensquare
indicatesfasting.Normalrangesoflaboratoryvaluesareindicatedbydashlines.Thepatientreceivedredbloodcelltransfusion(3units)
onday71andalsoreceivedG‐CSF(Neulasta)asindicated.
www.impactaging.com 11AGING,December2009,Vol.1No.12
again developed prolonged neutropenia and thrombo-
cytopenia, causing dose delays. For the third and
subsequent cycles, the patient fasted for 62 hours prior to
and 24 hours after chemotherapy. The patient not only
did not find hardship on carrying out the fasting but also
showed a faster recovery of her blood cell counts,
allowing the completion of the chemotherapy regimen
(gemcitabine 720mg/m2 on day 1 plus gemcitabine
720mg/m2 and TAX 80mg/m2 on day 8). During the fifth
cycle, she fasted under the same regimen and received a
full dose of gemcitabine (900mg/m2) and TAX (Table 2
and S2). Her complete blood count showed consistent
improvement during the cycles in which chemotherapy
was combined with fasting. A trend in which nadirs were
slightly less pronounced and the zeniths were
considerably higher in ANC, lymphocyte and WBC
counts was observed (Figure 7A, B, C, respectively;
Table S2). During the first and second cycle (ad libitum
diet) gemcitabine alone induced prolonged thrombo-
cytopenia, which took 11 and 12 days to recover,
respectively (Figure 7D; Table S2) but following the first
combined fasting-gemcitabine treatment (third and
subsequent cycles), the duration of thrombocytopenia
was significantly shorter (Figure 7D; Table S2).
Figure8.Laboratoryvaluesofbloodcellcountsforcase7.(A)Neutrophils;(B)Lymphocytes;(C)Whitebloodcells,WBC;(D)
Platelets;(E)Redbloodcells,RBC(F)Hemoglobin,Hgb;(G)Hematocrit,Hct;(H)Prostatespecificantigen(PSA)level.Filledtriangle
indicatesdayofchemotherapy;opensquareindicatesfasting,arrowindicatesabirateroneadministration.Normalrangesoflaboratory
valuesareindicatebydashlines.ThepatientalsoreceivedG‐CSF(Neulasta)asindicated;(I)Self‐reportedside‐effectsafter
chemotherapyforcase7.Datarepresenttheaverageof8cyclesofchemo‐fastingtreatments.
www.impactaging.com 12AGING,December2009,Vol.1No.12
Case 7
This is a 66-year-old Caucasian male who was
diagnosed in July 1998 with prostate adenocarcinoma,
Gleason score 8. A Prosta Scint study performed in the
same year displayed positive uptake of the radiotracer in
the right iliac nodes, consistent with stage D1 disease.
The patient was treated with leuprolide, bicalutamide
and finasteride. In December 2000, the diseases
progressed. He started on a second cycle with leuprolide
acetate and also received High Dose Rate (HDR)
brachytherapy and external beam radiation with
Intensity Modulated Radiation Therapy (IMRT) to the
prostate and pelvis. In April 2008, a Combidex scan
revealed a 3 x 5 cm pelvic mass and left hydronephrosis
prompting initiation of TAX chemotherapy supplement-
ed with G-CSF. The patient received 60-75 mg/m2 of
TAX for 8 cycles. Throughout this period the patient
fasted for 60-66 prior to and 8-24 hours following
chemotherapy (Table 2). Side effects from fasting
included grade one lightheadedness (accordingly CTCAE
3.0) and a drop in blood pressure, none of which
interfered with his routine. Chemotherapy-associated
self-reported side effects included grade one sensory
neuropathy (Figure 8I). The patient’s ANC, WBC, plate-
let and lymphocyte levels remained in the normal range
throughout treatment, although he did develop anemia
(Figure 8A-G). PSA levels consistently decreased,
suggesting that fasting did not interfere with the
therapeutic benefit of the chemo-treatment (Figure 8H).
Case 8
This is a 53-year-old Caucasian female who was
diagnosed with stage IIA breast cancer (HER2+) in
2008. After a lumpectomy procedure, she received 4
cycles of adjuvant chemotherapy with TAX (75mg/m2)
and CTX (600mg/m2) every 21 days. For all 4 cycles
the patient fasted 64 hours prior to and 24 hours post
chemotherapy administration (Table 2). Self-reported
side effects included mild weakness and short-term
memory impairment (Figure 9).
Figure9.Sel
f
‐reportedside‐effectsafterchemotherapyforcase8.
Datarepresenttheaverageof4cyclesofchemo‐fastingtreatments.
www.impactaging.com 13AGING,December2009,Vol.1No.12
Case 9
This is a 48 year-old Caucasian female diagnosed with
breast cancer. Her adjuvant chemotherapy consisted of
4 cycles of doxorubicin (DXR, 110mg/dose) combined
with CTX (1100mg/dose) followed by weekly
paclitaxel and trastuzumab for 12 weeks. Prior to her
first chemotherapy treatment, the patient fasted for 48
hours and reported no adverse effects. During the
second and subsequent cycles the patient fasted for 60
hours prior to the chemotherapy followed by 5 hours
post drug administration (Table 2). She reported no
difficulties in completing the fasting. Although she
experienced alopecia and mild weakness, the patient did
not suffer from other commonly reported side effects
associated with these chemotherapy drugs (Figure 10).
Case 10
This is a 78 year-old Caucasian female diagnosed with
HER2 positive breast cancer. After mastectomy, six
cycles of adjuvant chemotherapy were prescribed with
CBDCA 400 mg (AUC= 6), TAX (75mg/m2)
complemented with G-CSF (Neulasta), followed by 6
months of trastuzumab (Table 2). Throughout the
treatment the patient fasted prior and after
chemotherapy administration. Although the patient
adopted fasting regimens of variable length, no severe
side effects were reported (Figure 11H; Table 2). Her
WBC, ANC, platelet and lymphocyte counts remained
within normal levels (Figure 11A-D) throughout the
treatment, but she developed anemia (Figure 11E-G).
Figure10.Sel
f
‐reportedside‐effectsafterchemotherapyforcase9.
Datarepresenttheaverageof4cyclesofchemo‐fastingtreatments.
www.impactaging.com 14AGING,December2009,Vol.1No.12
DISCUSSION
Dietary recommendations during cancer treatment are
based on the prevention or reversal of nutrient
deficiencies to preserve lean body mass and minimize
nutrition-related side effects, such as decreased appetite,
nausea, taste changes, or bowel changes [16].
Consequently, for cancer patients who have been
weakened by prior chemotherapy cycles or are
emaciated, many oncologists could consider a fasting-
based strategy to be potentially harmful. Nevertheless
Figure11.Laboratoryvaluesofbloodcellcountsforcase10.(A)Neutrophils;(B)Lymphocytes;(C)Whitebloodcells,WBC;(D)
Platelets;(E)Redbloodcells,RBC(F)Hemoglobin,Hgb;(G)Hematocrit,Hct.Filledtriangleindicatesdayofchemotherapy;opensquare
indicatesfasting.Normalrangesoflaboratoryvaluesareindicatedbydashlines.ThepatientalsoreceivedG‐CSF(Neulasta)asindicated.
(H)Self‐reportedside‐effectsafterchemotherapyforcase10.Datarepresenttheaverageof6cyclesofchemo‐fastingtreatments.
studies in cell culture and animal models indicate that
fasting may actually reduce chemotherapy side effects
by selectively protecting normal cells [9]. Following the
publication of this pre-clinical work, several patients,
diagnosed with a wide variety of cancers, elected to
undertake fasting prior to chemotherapy and shared
their experiences with us. In this heterogeneous group
of men and women fasting was safely repeated in
multiple cycles for up to 180 hours prior and/or
following chemotherapy. Minor complaints that arose
during fasting included dizziness, hunger, and headaches
www.impactaging.com 15AGING,December2009,Vol.1No.12
at a level that did not interfere with daily activities.
Weight lost during fasting was rapidly recovered in most
of the patients and did not lead to any detectable harm.
We obtained self-reported assessments of toxicity from
all 10 patients who incorporated fasting with their
chemotherapy treatments. Since many of the
chemotoxicities are cumulative, we evaluated serial data
including all the combined fasting- and non-fasting (ad
libitum diet) associated chemotherapy cycles (Figure
S1). Toxicity was graded utilizing a questionnaire based
on the Common Terminology Criteria for Adverse
Events of National Cancer Institute, version 3.0 (Table 1).
Although the lack of prospective collection of toxicity
data and grading are a significant limitation, this series
provide an early insight into the feasibility and potential
benefit of combining fasting with chemotherapy. Fewer
and less severe chemotherapy-induced toxicity was
reported by all the patients in combination with fasting,
even though fasting cycles were often carried out in the
later portion of the therapy (Figure S1). Nausea,
vomiting, diarrhea, abdominal cramps, and mucositis
were virtually absent from the reports of all 10 patients
in the cycles in which fasting was undertaken prior to
and/or following chemotherapy; whereas at least one of
these symptoms was reported by 5 out of the 6 patients
during cycles in which they ate ad libitum (Figure S1).
The four patients that fasted throughout their treatments
reported low severity for the majority of the side effects,
in contrast to the typical experience of cancer patients
receiving the same chemotherapy regimens (Figures 8I,
9, 10, 11H). For the 6 patients who received
chemotherapy with or without fasting, we compared the
severity of the self-reported side effects in the 2 closest
fasting/non-fasting (ad libitum diet) cycles in which the
patient received the same chemotherapy drugs at the
same dose. There was a general and substantial
reduction in the self-reported side effects in
combination with fasting (Figure 1). Symptoms such as
fatigue and weakness were reported to be significantly
reduced (p< 0.001 and p< 0.00193, respectively),
whereas vomiting and diarrhea were virtually absent in
combination with fasting (Figure 1). In addition, there
was no side effect whose average severity was reported
to be increased during fasting-chemotherapy cycles
(Figure 1 and Figure S1).
Challenging conditions such as fasting or severe CR
stimulate organisms to suppress growth and
reproduction, and divert the energy towards cellular
maintenance and repair to maximize the chance of
survival [17, 19]. In simple organisms such as yeast,
resistance to oxidants and chemotherapy drugs can be
increased by up to 10-fold in response to fasting/starve-
tion and up to 1,000-fold in those cells lacking
homologs of Ras, AKT and S6 kinase [9]. Nevertheless,
such protection and oxidative stress resistance is
completely reversed by the expression of oncogene-like
genes [9,18]. In mammals, the mechanism(s) responsib-
le for the protective effect of fasting against
chemotherapy induced-toxic side effects is not
completely understood. It may involve reduction in
anabolic and mitogenic hormones and growth factors
such as insulin and insuline-like growth factor 1 (IGF-1)
as well as up-regulation of several stress resistance
proteins[20-25]. In fact, mice with liver specific IGF-I
gene-deletion (LID) which have ~80% reduction of
circulating IGF-I and mice with genetic disruptions in
the IGF-I receptor (heterozygous knockout IGF-IR +/-)
or its downstream elements have been shown to be
more resistant against multiple chemotherapy agents
and oxidative stress, respectively [26, 27]. Alternatively,
fasting-dependent DSR may be, in part, mediated by
cell cycle arrest in normal cells whereas transformed
cells continue to proliferate, remaining vulnerable to
anticancer drugs [25, 28]. Although mutations driving
cancer progression are heterogeneous across tumor
types, the majority of the oncogenic mutations render
cancer cells independent of growth signals [28, 29],
which we hypothesize prevents cancer cells from
responding to the fasting-induced switch to a protected
mode [9]. Therefore, DSR would have the potential to
be applied independently of the cancer type. Although
this has not been yet demonstrated, the remarkable
effects of fasting on the down-regulation of a number of
growth factors and signal transduction pathways
targeted by anti-cancer drugs, including IGF-I and the
TOR/S6 kinase pathways, raises the possibility that it
could enhance the efficacy of cancer treatment drugs
and may even be as effective as some of them.
In summary, in this small and heterogeneous group of
cancer patients, fasting was well-tolerated and was
associated with a self-reported reduction in multiple
chemotherapy-induced side effects. Although bias could
affect the estimation of the side effects by the patients,
the case reports presented here are in agreement with the
results obtained in animal studies and provide prelimina-
ry data indicating that fasting is feasible, safe and has the
potential to differentially protect normal and cancer cells
against chemotherapy in humans. Nevertheless, only a
clinical trial, such as the randomized controlled clinical
trial currently carried out at the USC Norris Cancer Cen-
ter, can establish whether fasting protects normal cells
and increases the therapeutic index of chemotherapies.
METHODS
From April 2008 to August 2009, 10 unrelated patients
diagnosed with a variety of cancer volunteered to
www.impactaging.com 16AGING,December2009,Vol.1No.12
incorporate fasting with their chemo-treatments. We
invited these patients to complete a self-assessment
survey based on the Common Terminology Criteria for
Adverse Events of The National Cancer Institute
version 3.0. For the purpose of this study only, we
developed a questionnaire that contained 16 easy
identifiable and commonly reported side effects; the
seriousness of the symptoms was graded from 0 to 4
with each consecutive number corresponding to no side
effect/mild/moderate/severe and life threatening.
Adverse effects were further divided into 3 major
categories including, general, gastrointestinal and
central/peripheral nervous system side effects, (Table 1,
original questionnaire). The survey was delivered to
patients by mail, e mail or fax and every patient was
instructed to complete it 7 days after each treatment
cycle. Explanation and assistance to patient’s concern
were offered throughout the study. The eligibility
criterion to participate was subjected to those patients
that had voluntarily fasted prior and/or post
chemotherapy. Medical records including basic
demographical information, diagnosis, treatments,
imaging studies and laboratory analysis were also
retrospectively reviewed (Tables 2, 3). All the
aforementioned procedures were in compliance with the
Internal review Board of the University of Southern
California (USC).
ACKNOWLEDGEMENTS
We thank the patients, nurses and oncologists at a
number of clinics for devoting a considerable amount of
time to collecting the information contained in this case
series. We thank Dr. Charles Loprinzi and Dr. Roxana
Dronca for valuable comments and suggestions. This
study was sponsored in part by the Bakewell
Foundation.
CONFLICT OF INTERESTS STATEMENT
The authors of this manuscript have no conflict of
interest to declare.
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SUPPLEMENTARY MATERIAL
FigureS1.Sel
f
‐reportedside‐effectsafterchemotherapywithorwithoutfasting.
DatarepresentaverageofCTCAEgradereportedbyallthepatientsinthisstudy.18
chemotherapycyclesunderad‐libdietwerecomparedto46chemo‐fastingcycles.
www.impactaging.com 18AGING,December2009,Vol.1No.12
TableS1.Summaryofcase1
Days Treatment Fasting
(hr)
WBC ANC
Nadir* Recovery**
Zenith
Nadir* Recovery**
Zenith
Pre Post (Days) cell/uL (Days)
cell/uL
(Days) cell/uL (Days)
cell/uL
3 Docetaxel 140 40 15 1700 4 3900 15 561 4 2601
75mg/m2 +
Cyclophosphamide
600mg/m2 ad lib - 24 Docetaxel 12 1200 6 4600 12 120 6 3036
75mg/m2 +
Cyclophosphamide
600mg/m2 ad lib
-
45 Docetaxel 12 1500 8 4100 12 216 8 2932
75mg/m2 +
Cyclophosphamide
600mg/m2
66 Docetaxel 120 24 - - - 5200 - - - 3567
75mg/m2 +
Cyclophosphamide
600mg/m2
*Time(indays)toreachthelowestbloodcellcountafterchemotherapy.
**Time(indays)toreachnormallevelofbloodcellcountfromnadirday.
TableS2.Summaryofcase6
D
ays Treatment Fasting
(hr)
WBC ANC PLT
pre
post
G-
CSF
Nadir*
(Days)
cell/
uL
Recove
ry**
(Days)
Zenith
cell/ul
Nadir
*
(Days) cell/uL
Recove
ry**
(Days)
Zenith
cell/uL
Nadir*
(Days)
cell/u
L
Recove
ry**
(Days)
Zenith
cell/uL
4 Gemcitabine
(900mg/m2)
ad
Lib
− − 7 900 16 9000 7 400 16 7500 10 63 11 203
25 G-
CSF
27 Gemcitabine
(720mg/m2)
ad
Lib
− − 5 700 2 9200 5 700 2 8100 9 59 12 177
32 G-
CSF
33 G-
CSF
34 G-
CSF
36 G-
CSF
39 G-
CSF
41 G-
CSF
42 G-
CSF
43 Gemcitabine
(720mg/m2)
62 24 − 5 700 5 7800 5 700 5 6400 − −
48 G-
CSF
49 G-
CSF
50 G-
CSF
51 G-
CSF
53 Gemcitabine
720 mg/m2
Docetaxel
(80 mg/m2)
62 24 − 4 1800 3 11800 4 1300 3 10700 8 27 10 280
54 G-
CSF
67 Gemcitabine
(720mg/m2)
62 24 − 9 2700 5 21400 9 1600 2 18600 − −
76 Gemcitabine
720 mg/m2
Docetaxel
(80 mg/m2)
62 24 − − − − − 8 38 6 286
78 G-
CSF
91 Gemcitabine
(900mg/m2)
62 24 −
96 − 6 2300 1 16500 6 1500 1 15300 − − − −
97 G-
CSF
98 Gemcitabine
(900
mg/m2)
Docetaxel
(100
mg/m2)
62 24 − 6 2300 1 14600 6 1700 1 12800 7 16 7 250
99 G-
CSF
112 Gemcitabine
(900mg/m2)
−
*Time(indays)toreachthelowestbloodcellcountafterchemotherapy.
**Time(indays)toreachnormallevelofbloodcellcountfromnadirday.
www.impactaging.com 20AGING,December2009,Vol.1No.12
