Gemcitabine combined with sequential paclitaxel and carboplatin in patients with urothelial cancers and other advanced malignancies.
BACKGROUND
To investigate a novel schedule of gemcitabine (G), paclitaxel (P), and carboplatin (C), based on preclinical studies demonstrating greater activity and decreased toxicity of administering P prior to C.


METHODS
The effect of the P and C drug sequence on tumor cell viability was assessed with a tetrazolium assay on T24 bladder and DU145 prostate cancer cells. Patients with transitional cell cancer (TCC) and other advanced malignancies were treated with G and P on days 1, 8, and 15 of each 28 day cycle. C was administered on day 2 at an AUC of 5. Doses of G and P were varied among cohorts of three patients.


RESULTS
Preclinical studies demonstrated that the sequence of P followed by C induced greater cytotoxicity than the reverse sequence. The recommended phase II dose (RPTD) was defined as 70 mg/m2 P, 300 mg/m2 G, and C with AUC of 5. Therapy was well tolerated; fever and neutropenia occurred in only one patient at the RPTD. Grade 3 thrombocytopenia occurred in 5 of 21 patients treated at the RPTD. Out of all 37 patients treated on study, 9 achieved a partial tumor response (PR) and two patients achieved a complete response (CR). Out of the 15 patients with TCC, six had a PR and two had a CR.


CONCLUSIONS
Preclinical studies demonstrated that the sequence of paclitaxel followed by carboplatin was more effective than the opposite sequence. Administration of gemcitabine and paclitaxel followed by carboplatin was well tolerated and clinically active. GCP should be compared to other combination regimens under investigation for the treatment of TCC.
DiPaola
Robert S
RS
Department of Medicine, UMDNJ/Robert Wood Johnson Medical School, New Brunswick, NJ 08901, USA.
Rubin
Eric
E
Toppmeyer
Deb
D
Eid
Joseph
J
Butzbach
Debarah
D
Dvorzhinski
Dmitri
D
Capanna
Terry
T
Cairdella
Marie
M
Shih
Joe W
JW
Goodin
Susan
S
Todd
Mary B
MB
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage / Q000627:therapeutic use*; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy / Q000473:pathology; D002470:Cell Survival; D015331:Cohort Studies; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D017239:Paclitaxel / Q000008:administration & dosage / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000473:pathology; D019459:Urothelium / Q000473:pathology; D000093542:Gemcitabine
D003841:Deoxycytidine; D016190:Carboplatin; D017239:Paclitaxel; D000093542:Gemcitabine