Table 3 Toxicity of valproic acid (VPA)^a

				NCI – CTC grade
				1	2	3	4
VPA dose (mg kg⁻¹ day⁻¹)	No. of patients	Median duration (weeks)	Toxicity	(No. of patients)	(No. of patients)	(No. of patients)	(No. of patients)
VPA alone
10–30^b	17	6	Leukocytosis	2
			Thrombocytosis	1
			Anemia	2		2
			Nausea/vomiting	2
			Abdominal pain		1	1
			Asthenia		3
			Erithema		1
			Hepatic (ALP, LDH)		1
			Amylase	3	1
			Dyspnea (pleural eff.)				1
			Depr. consciousness	1
60–90^c	11	6	Thrombocytopenia	1
			Anemia	1	1	1	1^d
			Asthenia	1
			Constipation	1^d
			Sciatic pain		1
			Infection		2^d
			Creatinine	1
			Hematuria		1^d
			Hypoacusis	1^d
			Dyspnoea	1
			Ataxia			1
			Depr. consciousness	1^d	1
VPA in combination with chemoimmunotherapy
30	3	3	Anemia		1
			Asthenia		2
			Hepatic (AST)	1
			Tremors	1
60	12	14	Leukopenia	2	4
			Neutropenia		2	3
			Thrombocytopenia	3	1	4
			Anemia	2	3	1	1
			Nausea/vomiting	6
			Diarrhea	3	1
			Asthenia		2
			Ammonia	2
			Hepatic (any)	3
			Gastric pain	2
			Fever	1	1
			Hypocalcemia			1
			Depr. consciousness	3	3	1	1
			Other neurological^e	2	6	2	1
			Cerebral hemorrhage				1
			Urinary incontinence		1	1
90	3	3	Leukopenia		1
			Thrombocytopenia			1	1
			Anemia	1
			Hepatic (AST)	1
			Amylase	1
			Headache		1

^aOn 28 assessable patients. Each patient is reported in each section of the table (VPA alone, and VPA in combination with chemoimmunotherapy) within the row corresponding to the highest dose level he received during the pertinent period of therapy. Some patients had dose reductions of VPA already during the induction phase, and others had dose escalation during the combination phase. All patients except one had some kind of toxicity.
^bThree patients at 10 mg kg⁻¹ day⁻¹, 14 patients at 30 mg kg⁻¹ day⁻¹.
^c10 patients at 60 mg kg⁻¹ day⁻¹, one patient at 90 mg kg⁻¹ day⁻¹.
^d90 mg kg⁻¹ day⁻¹, with bladder progression of disease.
^eVertigo, hallucinations, headache, speech impairment, mood alteration, memory loss, paraesthesia, seizures, tremors, confusion.

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