Safety, tolerability, pharmacokinetics, and pharmacodynamics of an orally active novel camptothecin analog, DRF-1042, in refractory cancer patients in a phase I dose escalation study.
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| Abstract |
The objective of this study was to characterize the maximum tolerated dose (MTD), dose-limiting toxicities (DLT), pharmacokinetics, and antitumor effects of DRF-1042, a novel camptothecin analog, in refractory solid tumor patients. DRF-1042 was given for 5 consecutive days for 2 weeks, repeated every 3 weeks at 1.5 to 270 mg/m(2). Adverse events were monitored following NCI-CTC. Pharmacokinetics of lactone and total forms were determined using validated high-performance liquid chromatography (HPLC) and noncompartmental methods. Efficacy was evaluated applying World Health Organization (WHO) criteria. The 1st course was used to determine DLT and MTD. Twenty-five patients received 73 courses of therapy. Myelosuppression and diarrhea were DLTs. MTD was 120 mg/m(2)/day. AUC increased approximately linearly with dose. The t(1/2) for lactone and total forms was 9.9 and 29 hours, respectively. AUCs correlated significantly with nadir leucopenia and grade 4 diarrhea. Two complete responses (CRs) and 2 partial responses (PRs) were observed. In addition, 4 stable diseases were observed. The recommended phase II dose is 80 mg/m(2)/day.
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| Authors | Arani Chatterjee, Raghunadharao Digumarti, Rao N V S Mamidi, Kasiram Katneni, Vijay V Upreti, Anjna Surath, Maddali L Srinivas, Srihari Uppalapati, Sangeeta Jiwatani, Swaminathan Subramaniam, Nuggehally R Srinivas |
| Journal | Journal of clinical pharmacology (J Clin Pharmacol) Vol. 44 Issue 7 Pg. 723-36 (Jul 2004) ISSN: 0091-2700 [Print] England |
| PMID | 15199077 (Publication Type: Clinical Trial, Clinical Trial, Phase I, Journal Article) |
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