|
24 patients were treated at 12 dose levels (2.4-500
mg/m2/day) with NAMI-A as an i.v.
infusion over 3 h daily for 5 days every three
weeks. Although no formal common toxicity criteria
grade 3 developed, painful blisters, occurring
at 400 mg/m2/day and persisting with
500 mg/m2/day, was considered DLT.
MTD was estimated at 300 mg/m2/day,
a dose at which NAMI-A can be administered safely
as a 3-h i.v. infusion for 5 days, every 3 weeks.
The most relevant PK
values indicate:
a) a linear relationship between
dose and AUC;
b) plasma clearance of total
ruthenium: 0.17±0.09 liter/h;
c) terminal half-life: 50 ±19
h;
d) volume of distribution at
steady state of total ruthenium: 10.1 ±2.8
liters;
e) accumulation of ruthenium
in WBS not directly proportional to increasing
total exposure to ruthenium.
One Patient with pre-treated
and progressive NSCLC had stable disease for
21 weeks
|
Patient
characteristics:
| |
No.
of patients |
% |
| Total
number |
24 |
|
| Male/Female |
14/10
|
58/42
|
| Median
age (range) |
56(35-70) |
|
WHO performance status:
Previous
therapy:
| Radiotherapy,
systemic
therapy and surgery |
7 |
29 |
| Surgery
and systemic
therapy |
8 |
33
|
Radiotherapy
and
systhemic therapy |
3 |
13 |
| Systhemic
therapy |
6 |
25 |
Tumor
type:
Colon 5, Colorectal 2, NSCLC 2, Melanoma 2,
Ovary 2, Mesothelioma 2, Pancreas 2, Synovia
sarcoma 1, Bileduct carcinoma 1, Gastric 1,
Broncho Alveolar 1, Oesopharingeal 1, Liposarcoma
1, Leiomyosarcoma 1
|
