A phase II pharmacodynamic study of pyrazoloacridine in patients with metastatic colorectal cancer.
OBJECTIVE
To perform a phase II trial of pyrazoloacridine (PZA), a novel DNA intercalator, in patients with metastatic colorectal carcinoma and no previous therapy.


METHODS
PZA was administered at a dose of 750 mg/m2 intravenously over 3 h every 21 days. Pharmacokinetic studies to determine PZA plasma concentrations were performed.


RESULTS
No responses were seen in 14 response-evaluable patients. Patients received a median of two cycles of PZA (range 1-6). Toxicity included neutropenia and neurologic side-effects, which were > or = grade III in 73% and 14%, respectively. High plasma concentrations of PZA (Cmax) correlated with low neutrophil counts (P = 0.04).


CONCLUSIONS
PZA is inactive at this dose and schedule in colorectal cancer, and produces moderately severe toxicity.
Pelley
R
R
Experimental Therapeutics Program, The Cleveland Clinic Cancer Center, OH 44195, USA.
Ganapathi
R
R
Wood
L
L
Rybicki
L
L
McLain
D
D
Budd
G T
GT
Peereboom
D
D
Olencki
T
T
Bukowski
R M
RM
D000166:Acridines / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D003110:Colonic Neoplasms / Q000097:blood / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007364:Intercalating Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009422:Nervous System Diseases / Q000139:chemically induced; D009503:Neutropenia / Q000139:chemically induced; D011720:Pyrazoles / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D012004:Rectal Neoplasms / Q000097:blood / Q000188:drug therapy*
D000166:Acridines; D000970:Antineoplastic Agents; D007364:Intercalating Agents; D011720:Pyrazoles; C064541:NSC 366140