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Phase I Study of the Taxane BMS-188797 in Combination with Carboplatin Administered Every 3 Weeks in Patients with Solid Malignancies

Authors' Affiliations: ¹ Experimental Therapeutics and Phase I Programs, Department of Interdisciplinary Oncology; ² Biostatistics Core, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida; and ³ Bristol-Myers Squibb, Princeton, New Jersey

Requests for reprints: Daniel M. Sullivan, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL 33612. Phone: 813-979-3878; Fax: 813-979-7265; E-mail: sullivad{at}moffitt.usf.edu.

Rationale: BMS-188797 is one of several novel taxanes in ongoing clinical development. It has superior activity in experimental tumor models when compared with paclitaxel. BMS-188797 has a single C-4 modification, a 4-desacetyl-4-methylcarbonate, compared with paclitaxel.

Methods: We did a phase I study, in which a fixed dose of carboplatin was combined with a dose escalation schedule of BMS-188797, both administered once every 3 weeks, in patients with advanced solid malignancies.

Results: Thirty patients were treated, 11 at the proposed recommended phase II dose. The dose-limiting toxicity was myelosuppression. There was a linear relationship between administered dose of BMS-188797 and the measured area under the curve (AUC). There was significant interpatient variability of BMS-188797 AUC at the maximum tolerated dose. Two radiographic partial responses were observed: one patient with duodenal adenocarcinoma and one patient with esophageal adenocarcinoma (time on study, 19 and 30 weeks, respectively).

Conclusion: The recommended phase II dose for BMS-188797 and carboplatin administered on a once-every-3 week schedule is carboplatin AUC = 5 mg min/mL and BMS-188797 at a dose of 135 mg/m².

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