Phase I study of the taxane BMS-188797 in combination with carboplatin administered every 3 weeks in patients with solid malignancies.
BACKGROUND
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).


CONCLUSIONS
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/m(2).
Fishman
Mayer N
MN
Experimental Therapeutics and Phase I Programs, Department of Interdisciplinary Oncology, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL 33612, USA..
Garrett
Christopher R
CR
Simon
George R
GR
Chiappori
Alberto A
AA
Lush
Richard M
RM
Dinwoodie
William R
WR
Mahany
J Joseph
JJ
Dellaportas
Anne M
AM
Cantor
Alan
A
Gollerki
Ashwin
A
Cohen
Marvin B
MB
Sullivan
Daniel M
DM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome
C436443:BMS188797; D043823:Taxoids; D016190:Carboplatin