9-Aminocamptothecin by 72-hour continuous intravenous infusion is inactive in the treatment of patients with 5-fluorouracil-refractory colorectal carcinoma.
BACKGROUND
9-Aminocamptothecin (9AC) and its parent compound, camptothecin, have shown outstanding preclinical activity against colorectal carcinoma. Irinotecan (CPT-11), another camptothecin derivative, has demonstrated clinical activity in patients with 5-fluorouracil (5-FU)-refractory colorectal carcinoma.


METHODS
The authors performed a Phase II trial of 9AC involving patients with measurable metastatic colorectal carcinoma who had progressed through only one prior regimen of 5-FU-based chemotherapy. 9AC was given initially at a dose of 59 microg/m2/hour by continuous intravenous infusion for 72 hours, with treatments repeated every 14 days. Granulocyte-colony stimulating factor was given on Days 5-12.


RESULTS
Sixteen patients were treated on this trial. Fourteen were evaluable for response. Contrary to expectations, no major objective antitumor responses were observed. Eight patients experienced stable disease for a median of 4.1 months (range, 2.2-9.5 months). Toxicities, especially myelosuppression, were severe and necessitated a 15% reduction in the initial dose after the first 9 patients. Toxicities at this reduced dose remained unacceptable.


CONCLUSIONS
9AC did not demonstrate substantial activity against 5-FU-refractory colorectal carcinoma on the schedule studied. Toxicities at the doses and schedule studied were unacceptable in this patient population. Based on their results, the authors consider it unlikely that 9AC administered as a 72-hour continuous intravenous infusion will play a major role in the treatment of colorectal carcinoma.
Saltz
L B
LB
Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Kemeny
N E
NE
Tong
W
W
Harrison
J
J
Berkery
R
R
Kelsen
D P
DP
D000328:Adult; D000368:Aged; D000380:Agranulocytosis / Q000139:chemically induced; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D019008:Drug Resistance, Neoplasm; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D007262:Infusions, Intravenous; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009503:Neutropenia / Q000139:chemically induced; D013921:Thrombocytopenia / Q000139:chemically induced; D016896:Treatment Outcome
D000970:Antineoplastic Agents; C080125:9-aminocamptothecin; D005472:Fluorouracil; D002166:Camptothecin