EAL

ONC: Prostate Cancer (2006)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

The purpose of the research was to determine the effectiveness of modified citrus pectin [MCP] at increasing prostate-specific antigen doubling time [PSADT].

Inclusion Criteria:

Biopsy-confirmed adenocarcinoma of the prostate
Untreated at time of entry into study
Low but progressively rising prostate-specific antigen [PSA] levels (< 10 ng/ml)
Biochemical PSA failure following an attempt at local curative therapy (radical prostatectomy, external beam radiation, or cryosurgery)
At least 3 rising PSA levels documented prestudy over no less than a 6-month interval
If patient had been treated with androgen-deprivation therapy [ADT], he must have had a stable serum testosterone level (> 150 ng/ml) at least 6 months prior to inclusion in the study

Exclusion Criteria:

Not specifically mentioned; it is assumed that patients who did not meet inclusion criteria were excluded

Description of Study Protocol:

Recruitment:

The subjects were prostate cancer patients at the Daniel Freeman Memorial Hospital

Design:

Initial evaluation included:
- Baseline physical examination by physician
- System review
- Performance status assessment using Eastern Cooperative Oncology Group [ECOG] assessment
- PSA, chemistry, and hepatic panels
Each subject served as his own control, since the rate of PSA change or PSADT was being compared before and after intervention
All subjects were instructed to make no changes in their usual diet, use of nutritional supplements, or current prescription medications during the pre- and post-study period
Each study participant received Pecta-Sol (Econugenics Santa Rosa, CA) in 1800 mg, powder-filled capsules
- Subjects consumed 14.4 g MCP, or 18 capsules, each day
- The capsules were taken in three divided doses, along with eight ounces water or fruit juice
Patient tolerability of Pecta-Sol was assessed by comparing weekly self-assessment diaries with baseline assessments
No formal method of measuring study compliance was used; however, investigators questioned clients monthly about compliance and it was thought to be good
The rate of change in PSA or the PSADT was measured before and after the start of MCP
Patients took Pecta-Sol for 12 months

Blinding used (if applicable): NA

Intervention (if applicable):

The intervention was the use of MCP
- Citrus pectin is found in the peel and pulp of citrus fruits
  - Complex polysaccharide with galactosyl (sugar carbohydrate) residues
- MCP is citrus pectin that has been chemically altered in the laboratory to produce smaller, shorter chain molecules
  - MCP is more easily absorbed in the intestinal tract than citrus pectin
Prostate cancer research indicates that PSA levels continue to increase if there is no intervention
- The increase in PSA is expressed as a constant linear rate with time, log PSA
- Because serum PSA appears to be a reliable marker of cancer growth, an increased PSADT should indicate decrease cancer growth

Statistical Analysis:

The spline fit method was used to compare pre- and post-treatment PSADT measurements
- A single regression analysis is used for all pre- and post-treatment data to fit a broken line, with the break occurring at initiation of treatment
P < 0.05

Data Collection Summary:

Timing of Measurements:

At study initiation:
- Baseline physical examination by physician
- System review
- Performance status assessment using Eastern Cooperative Oncology Group [ECOG] assessment
- PSA, chemistry, and hepatic panels
System review, ECOG assessment, PSA, chemistry, and hepatic panels were completed every 4 weeks
- PSA measurements were taken in a single laboratory by the same technician
Self-assessment diaries were examined weekly

Dependent Variables

Variable 1:
- Rate of change in PSA, expressed as PSADT, before and after the start of treatment

Independent Variables

Prostate cancer
Use of MCP

Control Variables

Each subject served as his own control
- Rate of change in PSA prior to treatment and rate of change in PSA post-treatment were compared

Description of Actual Data Sample:

Initial N: N = 13 males

Attrition (final N): N = 10 males

3 subjects withdrew due to mild gastrointestinal side effects
- 2 withdrew due to mild abdominal cramping
- 1 withdrew due to mild diarrhea

Age: Mean 69.6 yrs [62 - 79]

Ethnicity: Not mentioned

Other relevant demographics: Not provided

Anthropometrics

Pre-study PSA (ng/ml) : 1.103 [1.020 - 4.2]
Pre-study baseline testosterone (ng/ml) : 389.0 [210 - 587]

Location: Daniel Freeman Memorial Hospital

Summary of Results:

PSA doubling time before and after MCP

Patient	PSA doubling time in months, Pre - MCP	PSA doubling time in months, Post - MCP	Percent increase	Statistical Significance of Difference
#1	3.97	13.43	238	< 0.0001
#2	1.12	2.83	152.5	0.0014
#3	3.3	7.66	132	0.0002
#4	30.82	54.93	78	0.2352
#5	10.49	7.96	-24	0.8279
#6	3.64	3.28	-10	0.5667
#7	1.96	5.56	183.6	0.0004
#8	2.33	3.24	38.9	0.01
#9	6.596	33.3	404.8	<0.0001
#10	5.18	50.13	867.7	0.00065

Other Findings

Eight of ten evaluable patients had an increase in PSADT post-study
Seven of ten had a statistically significant increase in PSADT
No patient's absolute PSA decreased
MCP was well tolerated by all 10 patients evaluated
- 3 of the intial 13 patients withdrew due to mild gastrointestinal side effects
- No serious side effects were noted

Author Conclusion:

The authors concluded that seven (70%) of 10 patients had a statistically significant increase in PSADT after taking MCP for 12 months, when compared to before taking MCP.
The authors state that because rising PSA levels are associated with progression of cancer, it would seem that increasing PSADT would mean slower cancer progression, and possibly longer survival.
PSADT has a well-established use as a predictor of those who will develop progressive disease, but it has not been established whether increasing PSADT will impact development of metasteses or survival.
The authors note the following study limitations:
- Tumor volume was not directly measured, so it is not known whether changes resulted from the death of cancer cells or from some other mechanism
- The 12-month study period was long enough to evaluate the effect of MCP on PSA; however, it was not long enough to evaluate survival
The authors call for further research on the role of MCP in prostate cancer treatment

Funding Source:

University/Hospital:

University of California at Los Angeles,

Reviewer Comments:

Very small sample size
No formal method of assessing compliance with MCP regimen or dietary instructions
Study period was not long enough to assess impact of intervention on survival
Spline fit method of statistical analysis was appropriate and effective
23% dropout rate due to gastrointestinal side effects

Quality Criteria Checklist: Primary Research
Relevance Questions
	1.	Would implementing the studied intervention or procedure (if found successful) result in improved outcomes for the patients/clients/population group? (Not Applicable for some epidemiological studies)	Yes
	2.	Did the authors study an outcome (dependent variable) or topic that the patients/clients/population group would care about?	Yes
	3.	Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to dieteticspractice?	Yes
	4.	Is the intervention or procedure feasible? (NA for some epidemiological studies)	Yes

Validity Questions
1.	Was the research question clearly stated?		Yes
	1.1.	Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified?	Yes
	1.2.	Was (were) the outcome(s) [dependent variable(s)] clearly indicated?	Yes
	1.3.	Were the target population and setting specified?	Yes
2.	Was the selection of study subjects/patients free from bias?		???
	2.1.	Were inclusion/exclusion criteria specified (e.g., risk, point in disease progression, diagnostic or prognosis criteria), and with sufficient detail and without omitting criteria critical to the study?	Yes
	2.2.	Were criteria applied equally to all study groups?	Yes
	2.3.	Were health, demographics, and other characteristics of subjects described?	Yes
	2.4.	Were the subjects/patients a representative sample of the relevant population?	???
3.	Were study groups comparable?		N/A
	3.1.	Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT)	N/A
	3.2.	Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline?	N/A
	3.3.	Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.)	No
	3.4.	If cohort study or cross-sectional study, were groups comparable on important confounding factors and/or were preexisting differences accounted for by using appropriate adjustments in statistical analysis?	N/A
	3.5.	If case control study, were potential confounding factors comparable for cases and controls? (If case series or trial with subjects serving as own control, this criterion is not applicable.)	N/A
	3.6.	If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")?	N/A
4.	Was method of handling withdrawals described?		Yes
	4.1.	Were follow-up methods described and the same for all groups?	Yes
	4.2.	Was the number, characteristics of withdrawals (i.e., dropouts, lost to follow up, attrition rate) and/or response rate (cross-sectional studies) described for each group? (Follow up goal for a strong study is 80%.)	Yes
	4.3.	Were all enrolled subjects/patients (in the original sample) accounted for?	No
	4.4.	Were reasons for withdrawals similar across groups?	N/A
	4.5.	If diagnostic test, was decision to perform reference test not dependent on results of test under study?	N/A
5.	Was blinding used to prevent introduction of bias?		No
	5.1.	In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate?	N/A
	5.2.	Were data collectors blinded for outcomes assessment? (If outcome is measured using an objective test, such as a lab value, this criterion is assumed to be met.)	No
	5.3.	In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded?	N/A
	5.4.	In case control study, was case definition explicit and case ascertainment not influenced by exposure status?	N/A
	5.5.	In diagnostic study, were test results blinded to patient history and other test results?	N/A
6.	Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described?		Yes
	6.1.	In RCT or other intervention trial, were protocols described for all regimens studied?	Yes
	6.2.	In observational study, were interventions, study settings, and clinicians/provider described?	N/A
	6.3.	Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect?	Yes
	6.4.	Was the amount of exposure and, if relevant, subject/patient compliance measured?	No
	6.5.	Were co-interventions (e.g., ancillary treatments, other therapies) described?	Yes
	6.6.	Were extra or unplanned treatments described?	N/A
	6.7.	Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups?	N/A
	6.8.	In diagnostic study, were details of test administration and replication sufficient?	N/A
7.	Were outcomes clearly defined and the measurements valid and reliable?		Yes
	7.1.	Were primary and secondary endpoints described and relevant to the question?	Yes
	7.2.	Were nutrition measures appropriate to question and outcomes of concern?	Yes
	7.3.	Was the period of follow-up long enough for important outcome(s) to occur?	Yes
	7.4.	Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures?	Yes
	7.5.	Was the measurement of effect at an appropriate level of precision?	Yes
	7.6.	Were other factors accounted for (measured) that could affect outcomes?	No
	7.7.	Were the measurements conducted consistently across groups?	N/A
8.	Was the statistical analysis appropriate for the study design and type of outcome indicators?		Yes
	8.1.	Were statistical analyses adequately described and the results reported appropriately?	Yes
	8.2.	Were correct statistical tests used and assumptions of test not violated?	Yes
	8.3.	Were statistics reported with levels of significance and/or confidence intervals?	Yes
	8.4.	Was "intent to treat" analysis of outcomes done (and as appropriate, was there an analysis of outcomes for those maximally exposed or a dose-response analysis)?	No
	8.5.	Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)?	N/A
	8.6.	Was clinical significance as well as statistical significance reported?	No
	8.7.	If negative findings, was a power calculation reported to address type 2 error?	N/A
9.	Are conclusions supported by results with biases and limitations taken into consideration?		Yes
	9.1.	Is there a discussion of findings?	Yes
	9.2.	Are biases and study limitations identified and discussed?	Yes
10.	Is bias due to study's funding or sponsorship unlikely?		???
	10.1.	Were sources of funding and investigators' affiliations described?	No
	10.2.	Was the study free from apparent conflict of interest?	???