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9‐aminocamptothecin by 72‐hour continuous intravenous infusion is Inactive in the treatment of patients with 5‐fluorouracil‐refractory colorectal carcinoma
Author(s) -
Saltz Leonard B.,
Kemeny Nancy E.,
Tong William,
Harrison John,
Berkery Regina,
Kelsen David P.
Publication year - 1997
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/(sici)1097-0142(19971101)80:9<1727::aid-cncr5>3.0.co;2-b
Subject(s) - medicine , fluorouracil , colorectal cancer , refractory (planetary science) , irinotecan , regimen , population , carcinoma , chemotherapy , camptothecin , gastroenterology , oncology , cancer , surgery , chemistry , physics , environmental health , organic chemistry , astrobiology
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 μg/m 2 /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. Cancer 1997; 80:1727‐32. © 1997 American Cancer Society.