Cancer chemotherapy and pharmacology
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Cancer Chemother. Pharmacol. · Jul 2002
Multicenter StudyA population analysis of the pharmacokinetics of Cremophor EL using nonlinear mixed-effect modelling.
The purpose of this study was to develop a population pharmacokinetic model for Cremophor EL used as a formulation vehicle for paclitaxel. ⋯ The population model was able to adequately describe the pharmacokinetic parameters and influence of covariates on the pharmacokinetics of Cremophor EL. This model can be used when studying the relationship between the pharmacokinetics and toxicity of Cremophor EL, and the drug's influence on the pharmacokinetics of paclitaxel.
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Cancer Chemother. Pharmacol. · May 2002
ReviewTreatment of relapsed aggressive lymphomas: regimens with and without high-dose therapy and stem cell rescue.
Treatment of aggressive lymphoma in relapse is difficult. Patients who initially present with these diseases often know they have a malignancy considered curable in many cases, and diagnosis of relapse can be devastating. For this reason, it is useful to know the individual patient's risk of relapse prior to starting initial therapy, since it may be appropriate to treat patients with poor prognoses with intensive programs or investigational studies. ⋯ These factors predicted outcome: B symptoms, extranodal disease, and complete response less than 1 year. Finally, we have recently studied paclitaxel in combination with topotecan for relapsed and refractory aggressive lymphomas. These and newer combinations should be further developed to treat patients in relapse of aggressive lymphomas.
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Cancer Chemother. Pharmacol. · May 2002
Clinical TrialPharmacokinetics of oxaliplatin (NSC 266046) alone and in combination with paclitaxel in cancer patients.
Oxaliplatin (OPT), a third-generation platinating agent, is currently being evaluated in a phase II clinical trial in head and neck cancer patients and in a phase I clinical trial in combination with paclitaxel (TXL). ⋯ OPT clearance may be enhanced by TXL when the two agents are used in combination in patients. The Pt-DNA adduct level in peripheral WBC was found to be a good indicator for oxaliplatin exposure in patients, and should be further exploited for potential tumor drug exposure.
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Cancer Chemother. Pharmacol. · May 2002
Enhanced antitumor activity of irofulven in combination with thiotepa or mitomycin C.
Irofulven (6-hydroxymethylacylfulvene, MGI 114, NSC 683863) is a semisynthetic derivative of illudin S, a toxin present in the Omphalotus mushroom. Irofulven has demonstrated activity against a broad range of solid tumors in both xenograft models and human trials. The potential application of administering irofulven in combination with aziridine-containing chemotherapeutic agents was evaluated in this study. ⋯ These results indicate that the therapeutic activity of irofulven is enhanced when combined with mitomycin C or thiotepa, and further evaluation of these combinations is therefore warranted.
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Cancer Chemother. Pharmacol. · Apr 2002
P-glycoprotein inhibition by the multidrug resistance-reversing agent MS-209 enhances bioavailability and antitumor efficacy of orally administered paclitaxel.
Recent studies in humans and mice have demonstrated that intestinal P-glycoprotein plays a causative role in the limited absorption of orally administered paclitaxel. Multidrug resistance (MDR)-reversing agents, such as cyclosporin A and PSC 833, are known to increase the systemic exposure to orally administered paclitaxel by enhancing absorption in the intestinal tract and decreasing elimination via the biliary tract. In this study, we demonstrated that coadministration of the MDR-reversing agent MS-209, which is known to inhibit P-glycoprotein function by direct interaction, improved the bioavailability of orally administered paclitaxel and consequently enhanced its antitumor activity. ⋯ The present study suggests that coadministration of MS-209 may be a useful way to improve the bioavailability of drugs not suitable for oral administration due to elimination via the intestinal tract.