Dose-escalating and pharmacologic study of oxaliplatin in adult cancer patients with impaired hepatic function: A national cancer institute organ dysfunction working group study Journal Article
| Authors: | Synold, T. W.; Takimoto, C. H.; Doroshow, J. H.; Gandara, D.; Mani, S.; Remick, S. C.; Mulkerin, D. L.; Hamilton, A.; Sharma, S.; Ramanathan, R. K.; Lenz, H. J.; Graham, M.; Longmate, J.; Kaufman, B. M.; Ivy, P. |
| Article Title: | Dose-escalating and pharmacologic study of oxaliplatin in adult cancer patients with impaired hepatic function: A national cancer institute organ dysfunction working group study |
| Abstract: | Purpose: To determine the toxicities, pharmacokinetics, and maximally tolerated doses of oxaliplatin in patientswith hepaticimpairment and to develop formal guidelines for oxaliplatin dosing in this patient population. Experimental Design: Sixty adult cancer patients with variable hepatic function received i.v. oxaliplatin ranging from 60 to130 mg/m2 every 3 weeks. Patients were stratified by levels of total bilirubin, aspartate aminotransferase (AST), and alkaline phosphatase (AP) into five cohorts based on the degree of hepaticdy sfunction: control group A [bilirubin, AST, and AP ≤ upper limit of normal (ULN)], mild dysfunction group B (bilirubin V ULN, ULN ≤ AST V 2.5 x ULN, or ULN < AP ≤ 5 x ULN), moderate dysfunction group C (ULN < 2.5 x ULN, or AP > 5 x ULN), severe dysfunction group D (bilirubin > 3.0 mg/dL, any AST, and any AP), and liver transplantation group E (any bilirubin, any AST, and any AP). Doses were escalated in cohorts of three patients, and urine and plasma ultrafiltrates were assayed for platinum concentrations. Results: Dose escalation of single-agent oxaliplatin to 130 mg/m2 was well tolerated in all cohorts. Platinum clearance did not correlate with any liver function test. Two of 56 assessable patientswith a diagnosis of laryngeal carcinoma and cervical adenocarcinoma experienced partial responses lasting 3 and 5.5 months. Conclusions: Oxaliplatin at 130 mg/m 2 every 3 weeks was well tolerated in all patients with impaired liver function. Dose reductions of single-agent oxaliplatin are not indicated in patients with hepatic dysfunction. © 2007 American Association for Cancer Research. |
| Keywords: | adult; aged; aged, 80 and over; middle aged; major clinical study; drug tolerability; fatigue; larynx carcinoma; liver transplantation; antineoplastic agents; liver dysfunction; cancer patient; cancer diagnosis; neoplasms; multiple cycle treatment; sensory neuropathy; nausea; peripheral neuropathy; practice guideline; dose-response relationship, drug; drug dose escalation; drug hypersensitivity; hyperglycemia; alkaline phosphatase; aspartate aminotransferase; bilirubin; correlation analysis; disease severity; platinum; liver diseases; urine; liver function test; maximum tolerated dose; oxaliplatin; organoplatinum compounds; metabolic disorder; uterine cervix carcinoma; liver function tests |
| Journal Title: | Clinical Cancer Research |
| Volume: | 13 |
| Issue: | 12 |
| ISSN: | 1078-0432 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2007-06-15 |
| Start Page: | 3660 |
| End Page: | 3666 |
| Language: | English |
| DOI: | 10.1158/1078-0432.ccr-06-2385 |
| PUBMED: | 17575231 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 16" - "Export Date: 17 November 2011" - "CODEN: CCREF" - "Source: Scopus" |
