Phase II study of Mitonafide in advanced and relapsed colorectal cancer.
BACKGROUND
This study investigated the antitumoral activity in colorectal cancer and toxicity of a 5-day continuous infusion of a new cytostatic agent, Mitonafide, that had previously shown to be neurotoxic when administered as a short daily x 5 days infusion.


METHODS
Seventeen chemotherapy-naive patients with advanced or relapsed colorectal cancer and measurable disease entered the study. All but one received a 120-hour (5-day) continuous infusion of Mitonafide at a starting dose of 200 mg/m2/day every 3 weeks. Toxicity evaluation was performed after each course and response assessment every 2 courses using the standard World Health Organization (WHO) criteria completed by the "Mini-mental state" test for cognitive status examination.


RESULTS
Sixteen patients received a total of 41 courses of Mitonafide which resulted to be severely myelotoxic. In total, 13/16 patients had WHO grade 3-4 neutropenia, 7 of them with infection, and the treatment had to be stopped in 3 patients after only 1 course due to excessive toxicity. No central nervous system toxicity was observed. No objective responses were evidenced.


CONCLUSIONS
At the dose and schedule of administration used, Mitonafide is not active in colorectal cancer and induces severe myelotoxicity thus not deserving further studies in this indication.
Hospital Universitari Germans Trias i Pujol, Badalona, Spain.
A
A
Abad
C
C
Grávalos
A
A
Font
F
F
Molina
M T
MT
Díaz-Puente
X
X
Fabregat
A
A
Benavides
M
M
Martín
D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007094:Imides / Q000009:adverse effects / Q000627:therapeutic use*; D007546:Isoquinolines / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D053644:Naphthalimides
D000970:Antineoplastic Agents; D007094:Imides; D007546:Isoquinolines; D053644:Naphthalimides; C019215:mitonafide