A Phase I Study of Cantuzumab Mertansine Administered as a Single Intravenous Infusion Once Weekly in Patients with Advanced Solid Tumors

DOI: 10.1158/1078-0432.CCR-04-0088 Published July 2004

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Fig. 1.
Trough plasma concentration versus number of doses (or weeks of treatment) for a single patient treated at 96 mg/m². Drug accumulation is demonstrated by increasing serum trough concentrations of cantuzumab mertansine over time for 1 patient treated for ∼1 year.

Table 1

Patient characteristics

Characteristic	No. of patients
No. of patients	39
Sex
Male	24
Female	15
Age, years
Median	61
Range	36–81
ECOG^a performance status
0	14
1	24
2	1
Prior therapy
None	2
Chemotherapy only	26
Chemotherapy and radiotherapy	10
Tumor type
Colon and rectum	24
Pancreas	8
Unknown primary	3
Lung	2
Gastric	1
Peritoneum	1

Table 3

Summary of toxicities greater than grade 1 in the 21-day determinative period

Dose level (mg/m²)	No. of patients	No. of patients with DLT^a	Elevated AST/ALT		Elevated alkaline phosphatase		Elevated total bilirubin		Elevated amylase/lipase		Anemia		Fatigue		Nausea		Diarrhea
			Grade 2	Grade 3	Grade 2	Grade 3	Grade 2	Grade 3	Grade 2	Grade 3	Grade 2	Grade 3	Grade 2	Grade 3	Grade 2	Grade 3	Grade 2	Grade 3
40	1
60	1
80	3
96	4												1
115	23	1	7		5	1	1		1	1	2		3		1		1
138	7	3	1	3^b			2						2	1^b

a DLT, dose-limiting toxicity; AST, aspartate aminotransferase; ALT, alanine aminotransferase.
b This event constituted a DLT.

Table 4

Pharmacokinetic parameters

Dose (mg/m²)	n	AUC_last (mg·h/liter)^a	Cmax (mg/liter)	Vd (liter)	t_1/2 (h)	AUC_last/dose (h/ml)
40	1	216	10.7	5.35	13	3.6
60	1	927	34.0	4.04	22	8.1
80	3	1582 (338)	43.5 (1.2)	5.53 (1.54)	39 (2)	10.2 (2.9)
96	3	1987 (553)	51.2 (5.8)	4.85 (0.77)	37 (9)	10.8 (3.3)
115	5	2650 (999)	73.5 (17.3)	4.06 (1.02)	40 (19)	11.7 (4.2)
138	5	3463 (1131)	80.8 (20.8)	4.58 (0.96)	41 (9)	12.8 (5.0)

a AUC_last, area under the plasma concentration-time curve from the time of dosing to the last observable concentration; Cmax, maximum observed plasma concentration; Vd, volume of distribution; t_1/2, terminal half-life.