Mitomi 1992.

Study characteristics
Methods	Study design: parallel RCT Study location: Japan Study dates: enrolment March 1985‐February 1987 Recruitment: patients recruited by attending physicians at 25 institutions in Kanagawa Prefecture. Number screened / eligible: 462/448 Inclusion criteria: primary cancer of the colon and rectum, any TN1, 2, 3MO or T4NOMO; macroscopically curative resection, under 75 years old, informed consent Exclusion criteria: had received cancer therapy before resection, multiple or duplicated carcinoma, severe complications, or abnormal laboratory values (WBC, PLT, protein, albumin, A/G, SGOT‐SGPT, urine protein or creatinine) Diagnostic criteria for inclusion/exclusion: primary cancer of the colon and rectum, any TN1, 2, 3MO or T4NOMO
Participants	Number randomised: 448; 227 control; 221 intervention Baseline imbalances: groups well‐matched on most variables except for rectal tumour size (larger in PSK group). Age: PSK: under 40 n = 14; 40‐49 n = 37; 50‐59 n=67; 60‐69 n = 71; 70+ n=32. Control: under 40 n = 13; 40‐49 n = 41; 50‐59 n = 74; 60‐69 n = 63; 70+ n = 36. Overall (calculated): under 40 n = 27; 40‐49 n = 78; 50‐59 n = 141; 60‐69 n = 134; 70+ n = 68. Sex:Coriolus versicolor (PSK): 125 men/96 women; Control: 128 men/99 women; Overall: 253 men/195 women Cancer type: colorectal. PSK group colon = 124 rectum = 97; Control group colon = 125 rectum n = 102; Overall colon = 249 rectum = 199 Cancer removed or present: removed If cancer was present,was it local or metastatic?: N/A What was the aim of chemo/radiotherapy (if applicable)? adjuvant Withdrawals and exclusions: PSK group withdrawals from chemotherapy treatment n = 30 (reasons described as similar to those in control group) and withdrawals from PSK treatment n=26 (report states that few side effects were caused by PSK); control group withdrawals from treatment n =27 (side effects n = 13; postoperative complications n = 9; reasons not reported n = 5)
Interventions	Coriolus versicolor intervention: oral protein‐bound polysaccharide K (PSK) manufactured by Kureha Chemical Industry Co. Ltd., 3 g/day, quote: "for over three years" plus chemotherapy as below Control intervention: chemotherapy alone Chemotherapy regimen: Mitomycin C (6.0 mg/m2) IV on day of and day after surgery, followed by oral 5‐FU (200 mg per day) administration quote: "for more than 6 months" Planned length of treatment: at least 6 months or until recurrence for chemotherapy and 3 years for PSK Setting: not described but presumably hospital outpatient Co‐interventions: none mentioned
Outcomes	1. Survival 2. Disease free‐survival 3. Disease recurrence 4. Treatment modification/withdrawal 5. Adverse events   Planned length of follow‐up from treatment initiation: plans unclear; follow‐up data to 5 years Time points: survival and recurrence reported at 1‐, 2‐, and 3‐year follow‐up. Adverse event assessment: no description of how adverse events were assessed. While the specific side effects for which treatment was abbreviated are reported and there is a total number of these in each group, there is no information on the timing or number of people experiencing side effects.
Notes	Study name: The Cooperative Study Group of Surgical Adjuvant Immunochemotherapy for Cancer of Colon and Rectum (Kanagawa) Funding source: no description of funding Declaration of interest: none declared
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "permuted blocks that were stratified according to the location of the carcinoma (colon vs. rectum) and the institution"
Allocation concealment (selection bias)	Unclear risk	No details reported
Blinding of participants and personnel (performance bias) Survival	Low risk	No blinding however no likely influence of unblinding upon survival
Blinding of participants and personnel (performance bias) Disease free survival/recurrence/response	Low risk	No blinding however no likely effect upon disease progression or recurrence
Blinding of participants and personnel (performance bias) Adverse events ‐ subjective	High risk	No blinding and likely affected experience of adverse events
Blinding of participants and personnel (performance bias) Adverse events ‐ objective	Unclear risk	No blinding and may have affected experience of adverse events
Blinding of outcome assessment (detection bias) Survival	Low risk	No blinding of outcome assessors reported however low risk of bias in ascertainment of death
Blinding of outcome assessment (detection bias) Disease free survival/recurrence/response	Unclear risk	No blinding described and unclear how assessment carried out.
Blinding of outcome assessment (detection bias) Adverse events ‐ subjective	High risk	No blinding and high risk of bias in assessment of outcome.
Blinding of outcome assessment (detection bias) Adverse events ‐ objective	Unclear risk	No blinding and possible risk of bias in assessment.
Incomplete outcome data (attrition bias) Survival	Low risk	Appears complete assessment and reporting.
Incomplete outcome data (attrition bias) Disease free survival/recurrence/response	Unclear risk	Unclear whether all data captured and reported.
Incomplete outcome data (attrition bias) Adverse events ‐ objective	Unclear risk	Unclear whether complete assessment was conducted and reported.
Incomplete outcome data (attrition bias) Adverse events ‐ subjective	Unclear risk	Unclear whether complete assessment was conducted and reported.
Selective reporting (reporting bias)	Unclear risk	No protocol or registration available.
Other bias	Low risk	No potential biases were apparent that do not correspond to the above categories (including study‐specific problems such as carryover in cross‐over trials, more general problems in study conduct such as contamination between intervention arms, or that a study is claimed to be fraudulent).