Final results of a randomised phase III study on adjuvant chemotherapy with 5 FU and levamisol in colon and rectum cancer stage II and III by the Norwegian Gastrointestinal Cancer Group

Figures & data

Table I.   Exclusion criteria.

1	Other prior malignancy except basal cell carcinoma or uterine cervix cancer in situ.
2	Prior cytotoxic therapy.
3	Pre- or postoperative radiation therapy.
4	Severe cardiac or pulmonary disease or other systematic diseases precluding standard chemotherapy.
5	Serum bilirubin above 40 µmol pr. litre, serum creatinine above 150 µmol pr. litre. Renal failure with creatinine clearance less than 60 ml pr. min.
6	Patients who are not able to undergo the full treatment because of psychological, social or geographic reasons.
7	Patients unlikely to start chemotherapy within 6 weeks from the day of surgery due to postoperative complications.
8	Patients with ulcerating colitis or Chron's disease.
9	Prior agranulocytosis or severe allergic drug reactions.

Table II.  Patient characteristics for evaluable patients.

Groups	Surgery alone	Adjuvant chemotherapy	All patients	p-value
Randomised	206	206	412	NS
Age (Years)
Median	62.3	60.3	61.3	p=0.50
Range	36.1–75.1	46.5–74.9	36.1–75.1
Mean	62.3	60.3	61.3	P=0.50
95% CI	61.1–63.5	59.0–61.7
Sex				NS
Male	106	109	215
Female	100	97	197
Localisation
Caecum	28	19	47
Ascending colon	31	42	73
Transversal colon	18	23	41
Descending colon	12	7	19
Sigmoid colon	52	58	110
Rectum	65	57	122	NS
<5 cm	20	13	33
6–10 cm	21	26	47
11–15 cm	24	18	42
Tumour stage				NS
T1	1	2	3
T2	21	9	30
T3	170	183	353
T4	14	12	26
Nodal stage				NS
N0	126	121	247
N1	56	56	112
N2	20	26	46
N3	4	3	7
TNM stage				NS
II (Dukes B)	126	121	247
Colon	90	95	185
Rectum	36	26	62
III (Dukes C)	80	85	165
Colon	51	54	105
Rectum	29	31	60
Interval from surgery to randomisation (days, median)	25,0	23.8		NS
Range			4–46

Figure 1.  Disease free survival (A) and cancer specific survival (B) for all randomised patients (206 patients in each group). Disease free survival (C) and cancer specific survival (D) for colon cancer stage III patients. Fluorouracil and levamisol was administered for one year as adjuvant chemotherapy after surgery versus surgery alone.

Figure 2.  Subgroup analysis according to gender. Disease-free survival (A) and cancer specific survival (B) for men, disease-free survival (C) and cancer specific survival (D) for women. Adjuvant therapy given was administration of fluorouracil and levamisol for one year.

Table III.  Recorded chemotherapy toxicity.

WHO Grade	0	1	2	3	4
Nausea	115	58	11	2	0
Vomiting	180	2	3	1	0
Stomatitis	171	8	6	1	0
Diarrhoea	161	12	10	3	0
Gastrointestinal total	102 (54.8%)	53 (28.5%)	23 (12.4%)	7 (3.8%)	1 (0.5%)
Leucopenia	178	6	0	0	2
Thrombocytopenia	184	1	0	0	1
Anemia	182	4	0	0	0
Haematological toxicity	176 (94.6%)	8 (4.3%)	0	0	2 (1.1%)
Dermatological	175	6	5	0	0
Conjunctivitis	177	8	1	0	0
Alopecia	179	6	1	0	0
Arthralgia	178	4	4	0	0
Cardiac symptoms	185	0	1	0	0
Others	174	7	4	0	1
Total toxicity	93 (50.0%)	54 (29.0%)	30 (7.1%)	6 (1.4%)	3 (0.7%)