Abstract | BACKGROUND: To evaluate the antitumor activity, toxicities, and pharmacokinetics (PK) of DX-8951f administered as a 30-min infusion daily for 5 days every 3 weeks in patients with fluorouracil-resistant metastatic colorectal carcinoma. PATIENTS AND METHODS: RESULTS: Fifteen patients were evaluable. Fifty-one courses of therapy were delivered (median 2). Responses were one minor response, six stable disease, and eight progressive disease. The principal adverse event was neutropenia, with grade 3 and 4 toxicities in three and eight patients, respectively. Non-hematologic toxicities were mild to moderate; the most common were fatigue, nausea, and diarrhea. Plasma concentrations of DX-8951 were well described using a linear two-compartment PK model. There was no evidence of nonlinearity in the elimination of PK or auto-inhibition or induction of DX-8951 clearance over the 5 days of administration. CONCLUSIONS:
DX-8951f at this dose and schedule had no significant activity in this patient population. The toxicity profile, mainly hematologic, was consistent with previous reports. The clearance and volume of distribution were not different from those previously reported.
|
Authors | Melanie E Royce, Eric K Rowinsky, Paulo M Hoff, John Coyle, Robert DeJager, Richard Pazdur, Leonard B Saltz |
Journal | Investigational new drugs
(Invest New Drugs)
Vol. 22
Issue 1
Pg. 53-61
(Jan 2004)
ISSN: 0167-6997 [Print] United States |
PMID | 14707494
(Publication Type: Clinical Trial, Clinical Trial, Phase II, Journal Article)
|
Chemical References |
- Antineoplastic Agents, Phytogenic
- exatecan
- Camptothecin
|
Topics |
- Adenocarcinoma
(drug therapy, secondary)
- Aged
- Antineoplastic Agents, Phytogenic
(adverse effects, blood, therapeutic use)
- Camptothecin
(adverse effects, analogs & derivatives, blood, therapeutic use)
- Colonic Neoplasms
(drug therapy, pathology)
- Female
- Humans
- Male
- Middle Aged
- Rectal Neoplasms
(drug therapy, pathology)
|