ADVERSE REACTIONS

Allergic sensitization, including anaphylactoid reactions and urticaria, has been reported following the administration of both oral and parenteral leucovorin. No other adverse reactions have been attributed to the use of leucovorin per se.

The following table summarizes significant adverse events occurring in 316 patients treated with the leucovorin/5-fluorouracil combinations compared against 70 patients treated with 5-fluorouracil alone for advanced colorectal carcinoma. These data are taken from the Mayo/NCCTG large multicenter prospective trial evaluating the efficacy and safety of the combination regimen.

PERCENTAGE OF PATIENTS TREATED WITH LEUCOVORIN/FLUOROURACIL FOR ADVANCED COLORECTAL CARCINOMA REPORTING ADVERSE EXPERIENCES OR HOSPITALIZED FOR TOXICITY

	(High LV) /5-FU (N=155)	(Low LV) /5-FU (N=161)	5-FU Alone (N=70)
	Any %	Grade 3+ (%)	Any %	Grade 3+ (%)	Any %	Grade 3+ (%)
Leukopenia	69	14	83	23	93	48
Thrombocytopenia	8	2	8	1	18	3
Infection	8	1	3	1	7	2
Nausea	74	10	80	9	60	6
Vomiting	46	8	44	9	40	7
Diarrhea	66	18	67	14	43	11
Stomatitis	75	27	84	29	59	16
Constipation	3	0	4	0	1
Lethargy/Malaise/Fatigue	13	3	12	2	6	3
Alopecia	42	5	43	6	37	7
Dermatitis	21	2	25	1	13
Anorexia	14	1	22	4	14
Hospitalization for Toxicity	5%	15%	7%

High LV = Leucovorin 200 mg/m 2, Low LV = Leucovorin 20 mg/m 2

Any = percentage of patients reporting toxicity of any severity

Grade 3+ = percentage of patients reporting toxicity of Grade 3 or higher