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The B-AHEAD 2 Trial
Randomised controlled trial of intermittent
versus continuous energy restriction during
adjuvant chemotherapy:
Dr Michelle Harvie
Research Dietitian The Nightingale and Prevent Breast Cancer Centre
University Hospital of South Manchester
Background
• Excess weight at diagnosis and weight gain after diagnosis increase risk of recurrence and mortality
(Chan et al Ann Oncology 2014
• Daily energy restriction and exercise is only partially effective for weight control in pts receiving chemotherapy for early breast cancer (-0.8Kg)
(Harvie et al B – AHEAD study)
• We have reported greater weight loss with intermittent vs. standard daily energy restriction in healthy overweight / obese women
(Harvie et al Br J Cancer 2013)
• Animal studies and case series suggest intermittent energy restriction reduce chemotherapy toxicity
(Brandhorst & Metabolism & Cancer Springer 2016)
Aim
•To test whether IER is feasible amongst women receiving chemotherapy for early breast cancer.
•To compare intermittent energy restriction vs. continuous energy restriction for :
Primary endpoints
• Changes in weight, body fat and fat free mass (DXA)
• Chemotherapy toxicity: -Self reported CTCAE scores, dose reduction, dose delay, hospitalisation, -Blood toxicity biomarkers; serum CK18 (epithelial toxicity) & plasma FLT 3 ligand (myelosuppression) (n = 55)
“Research findings may be coupled with suggestions and guesses to build up
concepts which by pyramided repetition become accepted”
Tannenbaum & Silverstone 1953 Early intermittent fasting researchers
Dept of Cancer research Michael Reese Hospital Chicago , USA
The IER and CER diets
70% of subjects Overweight / obese Aim to lose weight
Overall 25% energy restriction
IER 2 days low carb, 50-70% ER/wk 650-800kcal +5 days week Mediterranean diet
CER 25% energy restricted Mediterranean diet 7 days /week
30% of subjects Normal weight
Aim to maintain weight i.e. prevent wt gain
No energy restriction
IER 2 days low carb, 50-70% ER/wk 650-800kcal +5 days week Mediterranean diet cal
CER Mediterranean diet 7 days /week to meet estimated energy requirements
Outcomes assessed 3 weeks after final chemotherapy
n = 172
Scheduled to receive adjuvant or neoadjuvant chemotherapy
• 2 day / week IER (& physical activity)
• Individual face to face advice
• Telephone support (alternate weeks)
• Mailings (alternate weeks)
IER n=86
CER n=86
• Continuous energy restricted diet (&
physical activity)
• Individual face to face advice
• Telephone support (alternate weeks)
• Mailings (alternate weeks)
Study design 4
.5 –
6 m
onth
s o
f chem
oth
era
py
Inclusion criteria • Scheduled to have standard adjuvant or neoadjuvant chemotherapy
• Breast cancer stage I–III
• Any age >18 years
• BMI>19 kg / m2. We aim to prevent weight gain (normal wt) & promote wt loss (overweight / obese)
• Resident within Greater Manchester or Cheshire area
• Clear routine staging CT scan (for patients scheduled to receive neoadjuvant chemotherapy & patients with 4 or more axillary nodes)
Exclusion criteria • Metastatic disease
• Had previous chemotherapy within the last 2 years
• Serious cardiovascular, respiratory, musculoskeletal, digestive or psychiatric condition
• Medications affecting weight e.g. daily steroids (2-3 days with chemotherapy ok)
• Diabetics on insulin or sulphonylureas as could cause hypoglycaemia on
2 day diet
• Already commenced current course of chemotherapy
Recruitment
Not eligible n = 192 (29%)
25% - Already started chemotherapy
19% - Co morbidities
7% - Metastatic disease
5% - Low BMI
6% - IDDM
7% - Language
31% - Other
470 eligible
Not want to join n = 298 (45%)
18% - Did not want extra appts
15% - Not interested
12% - Too anxious
9% - Travel issues
5% - Not want to diet during chemo
3% - Already eats healthily
1% - Not want to be randomised
27% - Unknown
36% uptake of eligible women (8-50% in the centres)
Number screened in 11 cancer centres
n = 662
Baseline characteristics
IER ( n = 86) CER (n = 86)
Age (years) 51.3(9.0) 52.6(10.1)
BMI (Kg/m2) 28.1(6.1) 28.4(6.1)
Overweight/ obese/ normal wt - % 69/ 31 71/ 29
Premenopausal % 56 55
Ethnicity, Caucasian-% 96 88
Grade Invasive 1/2/3 /DCIS -% 4/ 30/ 64/ 2 5 / 43 / 51/ 1
ER +/ER- % 31 / 69 33 / 67
Chemotherapy -%
FEC –docetaxel
FEC-paclitaxel
Other
59
13
28
56
13
31
Adjuvant / neoadjuvant % 93/ 7 93/ 7
Current smoker % 7 3.5
Mean (SD)
Retention to trial Intermittent Continuous Withdrawn
2 1 Excluded after consent as not eligible
1 0 Developed mets during study
1 2 Too busy/Too many appts
6 3 Loss of contact
3 1 Not coping with chemo
2 2 Not tolerate diet
4 0 Other illness / feels too unwell
19 9 Total
22% 10% % Withdrawn
IER n = 86 CER n = 86
Calls received 7.6/10 7.5/10
% compliance with IER 2 days/ week during trial All patients (n = 86) Completers only (n = 67)
57% 62%
N/A
Adherence
Conclusion • Good uptake and retention show diet & exercise interventions
are feasible & welcomed amongst chemotherapy patients
• IER is feasible amongst chemotherapy patients
• Further analysis will inform the safety, harms of IER & CER i.e. dose information, hospitalisation, quality of life & objective blood markers of toxicity
Acknowledgements
Prevent Breast Cancer
Breast Cancer Research Trust
Our Trial Participants
Funding Lifestyle Research
Team
Co- investigators
Sacha Howell
Tony Howell
Anne Armstrong
Nigel Bundred
Lee Graves
Mark Mattson
Judy Adams
Louise Gorman
Mary Pegington
Nina Brogden
Claire Lindsay
Kath Sellers
Grace Cooper
Debbie McMullen
Pam Coates
Lesley Coates
Cheryl Barlow
Prevent BC Volunteers
PI’s & research nurses in
recruiting centres