- Click here for explanation of classification scheme.

To determine whether continuous intravenous nutrition (at hospital and home) could protect normal body composition during chemotherapy and thereby improve body functions measured as respiratory gas exchanges and exercise capacity.

• Testicular carcinoma

Not described

Recruitment Not described

 

Design Randomized clinical trial

 

Blinding used (if applicable) Not described

 

Intervention (if applicable)

• Subjects randomized prior to chemotherapy according to a computerized stratification algorithm including age, weight, weight loss, tumor stage, hostological classification of the tumor, surgical procedure and tumor markers to one of the following:
  • TPN plus spontaneous oral intake
  • Spontaneous oral intake (control group)
• All subjects were admitted to the hospital for nutritional assessment prior to chemotherapy
• Medical intervention
  • All subjects received cisplatinum, vinblastine/etoposide and bleomycin every three weeks
  • Subjects spent weeks 1, 4, 7, and in some cases, 10 in the hospital where chemotherapy was administered during Monday-Friday.
    • Ten subjects received chemotherapy for 8 weeks (4 in the TPN group, 6 in the control group)
    • 23 subjects received chemotherapy for 10 weeks (15 in the TPN group, 8 in the control group
  • Bleomycin was administered each Wed throughout the entire course at 30 mg
  • Cisplatinum was given IV (20 mg/m² body surface area) days 1-5.
  • Vinblastine (0.15 mg/kg body weight) was given days 1-2 to four subjects in the TPN group and five in the control group
  • Due to neurological side effects, etoposide (100 mg/m2 days 1-5) was given instead of vinblastine to 15 subjects in the TPN group and to 9 in the control group.
  • Central venous catheters were used for chemotherapy and infusions in all subjects.
• Study procedures
  • Dietary intake
    • All subjects were asked to record their daily spontaneous oral food intake during the whole chemotherapy period (56-70 days). Records were analyzed by a dietitian.
    • During the hospital stay all subjects were served ordinary hospital food (48% carbohydrate, 34% fat,  18% protein).
  • Biochemical tests and blood transfusions
  • Body composition
  • Exercise capacity

 

Statistical Analysis

• Values are given as mean ± SD.
• Alterations before and after treatment within groups were tested by a paired t-test, while mean values between groups were tested by Student's t-test.

 

Timing of Measurements

•  Baseline
  • Predicted REE calculated according to the Harris Benedict equation
• Before and after
  • REE
  • Resting heart rate
  • Triceps skinfold
  • Arm muscle circumference
  • Tumor markers
  • Urine creatinine
  • Plasma thyroid hormone levels
  • Plasma lactate
• Weekly
  • Weight
  • Hemoglobin: routine hospital measurement
  • Blood leukocytes: routine hospital measurement
  • Thrombocytes: routine hospital measurement 
  • Total body potassium
  • Total body nitrogen
  • Serum albumin

 

Dependent Variables

• Body composition
  • Total body potassium was measured in a total body counter
  • Total body nitrogen was measured by a whole body neutron activation technique
  • Total body water was measured by an isotope dilution technique with tritiated water as tracer
  • Anthropometrics
    • Triceps skinfold
    • Arm muscle circumference 
• Exercise capacity
  • Maximum physical exercise capacity was measured on a bed mounted cycle ergometer under standardized conditions.
  • Oxygen uptake and measurement of blood lactate concentrations were measured at maximum and submaximal exercise.
  • The cycle ergometer was constructed to deliver a constant load (watts) irrespective of the ergometer speed within a certain range as continuously shown to the patient on a speedmeter in front of the patient during exercise.
  • To determine maximal exercise capacity, subjects started to cycle at 60 watts for 3 min. The work load was increased by 10 watts every following minute until the subject stopped exercising due to exhaustion.
  • Heart rate was continuously monitored by EKG equipment.
  • Submaximal exercise started for 3 min without any load applied. Without interruption, a load was applied from the computer unit and the subject continued to cycle for 5-7 min at 20 watts followed by a 5 min rest period. The procedure was then r epeated at 35 and 50 watts, respectively.
  • Pulse rate and respiratory frequency were registered immediately before, during and after exercise as well as after the 5 min rest period.

 

Independent Variables

• TPN from day 1 for the duration of chemotherapy
  • Daily infusion with non-protein calories corresponding to 150% of REE determined by indirect calorimetry
  • Nitrogen: 0.2 kg/body weight/day
    • Amino acids were administered as a crystalline amino acid solution
  • Non-protein calories were comprised of 30% fat (Intralipid 20%) and 70% glucose 
  • Fat and water soluble vitamins and trace elements were added according to basal needs.
  • TPN was administered via an all in one system for 12-16 hours during the night
    • Specially trained nurses administered TPN in the home setting
  • Unrestricted oral intake

Control Variables

 

 

Initial N: 33 males

• TPN group: N=19
• Spontaneous oral intake: N=14

Attrition (final N): N=33

Age: 34 ± 4 years

Ethnicity: not described

Other relevant demographics: not described

Anthropometrics

• Height (cm): 181±2
• Weight reduction (kg): 4±1
• Weight index (ratio between actual vs expected weight): 0.86±0.02
• Weight (kg): 74.5±2.1
• Total body potassium (mmol): 4175±131
• Total body potassium index (ratio between actual vs expected body potassium): 1.0±0.02
• Total body nitrogen (kg): 1.90±0.1
• Triceps skinfold (mm): 10.1±1.0
• Arm muscle circumference (cm): 27.4±0.4
• Urine creatinine (mmol/24 hr): 15.1±0.9
• Albumin (g/l): 39.1±1
• Other information:
  • None had any impairment of the gastrointestinal tract.
  • Clinical staging performed by CT-scan or laparotomy.
  • None had been operated upon (testicular ablation and staging) within 6 weeks before treatment.

Location: University of Gothenburg, Sahlgrenska Hospital, Gothenburg, Sweden

 

 Total Dose of Chemotherapy. Mean ± SE

	TPN	Control
Weeks of Treatment	10.5±0.2	10.1±0.3
Tumor stage (1-4) (median)	3	3
Cisplatinum total dose (mg)	797±28	741±47
Vinblastine total dose (mg)	3782±259*	2633±472
Etoposide total dose (mg)	75±5	74±7
Bleomycin dose (mg)	257±14	259±12

*P<0.05 vs control group

1.  Chemotherapeutic treatment became comparable between the two groups, although there was a larger dose of Vinblastine given to the TPN subjects.
2. A difference in ß-HCG between the groups was due to one subject in the TPN group with extremely high levels. Recalculation of the results without this subject does not change any of the results of the study and gives a ß-HCG cocnentration of 19.8±14.7 IU/L beofre and 3.0±0.3 IU/L after treatment, respectively.

Tumor Markers and Blood Cell Concentrations (Mean±SE)

	TPN		Control
	Before	After	Before	After
Alpha fetoprotein (IU/ml)	110±72	6±1	7±2	6±1
ß-HCG (IU/l)	666±452	1681±1164	214±202	3±1
Erythrocyte Sedimentation Rate (mm/h)	32±10	47±11	27±12	33±5
Hemoglobin (g/l)	137±5	100±4§	143±5	110±5§
WBC (x109/l)	7.7±0.6	3.0±0.4§	7.7±0.7	3.8±0.9§
Thrombocyte blood count (x109/l)	297±23	132±19*§	329±35	224±26

 * P<0.05 TPN vs control after treatment

§ P<0.05 before vs after treatment within the groups

1. Both groups showed similar toxic reaction to the bone marrow with reduction in WBC and thrombocyte blood count.
2. The groups had similar sedimentation rates before and after treatment.

 

Body Composition (Mean±SE)

	TPN		Control
	Before	After	Before	After
Weight Index	0.86±0.02	0.88±0.02*	0.85±0.03	0.80±0.02
Weight (kg)	74.5±2.1	76.0±2.1§	73.8±3.2	69.6±3.2§
Total body potassium (mmol)	4175±131	3857±171§	4339±168	3873±223§
Total body potassium index	1.0±0.02	0.96±0.03§	1.0±0.04	0.93±0.05§
Total body nitrogen (kg)	1.90±0.1	1.57±0.1§	2.10±0.1	1.72±0.1§
Distribution volume of body water	44.0±1.7	44.8±3.01	45.6±3.1	41.1±2.21
Triceps Skinfold (mm)	10.1±1.0	13.1±1.5*§	9.9±0.8	8.5±0.8§
Arm muscle circumference (cm)	27.4±0.4	26.5±0.4§	27.3±0.7	25.6±0.9§
Urine creatinine (mmol/24 hr)	15.1±0.9	14.1±0.9	13.6±1.1	11.8±1.8
Albumin (g/L)	39±1	37±1§	39±2	39±1

 Body weight index and total body potassium index are the ratio between actual vs expected weight and body potassium.

* P<0.05 TPN vs control after treatment

§ P <0.05 before vs after treatment within groups

1. TPN group gained 2.3±1.0 kg and the control group lost 4.2±1.1 kg body weight which corresponded to 3±1 and 6±1%, respectively.
2. TPN group showed increased subcutaneous fat (TSF) by 31±9%, while the control group showed a decrease around 10%.
3. Fat was the only essential contribution to weight gain in the TPN group, since both groups showed comparable reductions in whole body protein content measured directly as total body nitrogen, and indirectly as total body potassium, arm muscle circumference and creatinine excretion.

 

Plasma Thyroid Hormone Concentrations and Energy Expenditure (mean ± SE)

	TPN		Control
	Before	Afte	Before	After
T4 (nmol/L)	17±2	15±1	16±1	17±1
T3 (nmol/L	1.9±0.08	2.3±0.1§	1.8±0.1	2.2±0.1§
Free T4 (pmol/L)	86±6	114±6§	92±5	126±10§
Free T3 (pmol/L)	6.1±0.3	6.2±0.4	5.8±0.6	5.9±0.6
Reversed T3 (nmol/L)	0.36±0.04	0.39±0.05	0.35±0.02	0.41±0.06
TSH (nmol/L)	1.8±2	1.8±0.1	1.9±0.2	1.6±0.2
Plasma lactate (mmol/L) Rest	1.1±0.08	1.4±0.2	1.1±0.1	1.1±0.1
Plasma lactate (mmol/L) after submaximal exercise	6.7±0.9	5.7±0.4	6.9±1.2	6.4±1.4
Resting heart rate (beats/min)	73±2	80±3	76±2	79±3
Maximal exercise capacity (watts/kg LBM)	4.9±0.2	4.2±0.2**	5.2±0.4	4.8±0.3***
REE (kcal/day)	1779±37	1650±85*	1624±61	1401±75§
Predicted REE (kcal/day)	1735±37	1777±42§	1759±62	1706±66§
Whole body oxygen uptake
(µmol/kg min)	155±5	132±5§	152±8	143±5
ml/kg min	3.47±0.11	2.96±0.11§	3.40±0.17	3.20±0.11
Respiratory quotient	0.77±0.01	0.79±0.02	0.80±0.01	0.79±0.02

* P<0.05 TPN vs control after treatment

§ P<0.05 before vs after treatment within the groups

1. REE was significantly higher in the TPN group after treatment.
2. Predicted energy expenditure calculated according to Harris-Benedict overestimated the enrngy expenditure at the end of treatment in both groups.
3. Plasma lactate concentrations were not different between the groups at rest or after submaximal exercise.
4. The reduction in maximum working capacity (watts) was identical between the groups at the end of chemotherapy (P<0.001), but the relationship between oxygen uptake and submaximal work was not significantly influenced by themotherapy or TPN in either of the two groups.
5. The decrease in maximal exercise ability (watts/kg LBM) was significant in the TPN group (P<0.01) but not in the control group (P<0.06).
6. The heart rate at maximum exercise did not differ between the groups before and after chemotherapy. The heart rate at the various levels of submaximal work loads was the same in both groups.

Other Findings

1. Average spontaneous oral caloric intake was 1014±153 kcal/day in the TPN group and 1484±200 kcal/day in the control group (P<0.07).
2. Average spontaneous oral protein intake was 35±5 g/day in the TPN group and 51.6±6 g/day in the control group (P<0.06).
   • TPN group: average total protein intake was around 1.7 g/kg/day (TPN + oral)
   • Control group: average total protein intake was around 0.7g/kg/day
3. Eleven subjects in the TPN group and 9 subjects in the control group provided complete food intake data.
4. TPN group was in energy balance as confirmed by maintained or increased body weight, while the control group was in overall negative energy balance.
   • It is estimated that energy balance was +850 kcal/day in the TPN group (mean total energy expenditure was 2286 kcal/day) and -532 kcal/day in the control group (mean total energy expenditure was 2016 kcal/day). The authors assumed that the activity related expenditure  was 125% of the REE.
5. Four septic episodes occurred (one in the control group, 3 in the TPN group) all of which were successfully treated with antibiotics after the catheter was withdrawn and  replaced after 3-4 days.

 

 

• This study demonstrates that TPN is insufficient to protect either body composition, whole body nitrogen sparing or working capacity when given daily for more than 8 weeks as adjunct to chemotherapy in patients with oral food intake reduced by 25-30%.
• Fat accumulation was the only measurable benefit.
• It is proposed that this is another example of the inefficiency of artificial nutrition to protect lean body mass in various groups of patients with upcoming or established undernutrition.

Government:	Swedish Medical Research Council
Not-for-profit	0 Foundation associated with industry:

Little information provided re: inclusion/exclusion criteria, although randomization scheme seems to account for some of this.

Attrition/intention to treat: All subjects completed chemotherapy so assuming all subjects completed study. Not stated in the paper or the tables.

Measurement of triceps skinfold depends on the skill of the technician. No info provided on the measurement process or the skill of the individual(s) performing measurement.

No sample size calculation. Small sample.

No information provided regarding compliance to TPN regimen. Compliance presented for food record intake and unsure whether this include volume of TPN received.