Abstract
Objectives. To evaluate the feasibility and activity of paclitaxel, carboplatin, and methotrexate in advanced transitional cell carcinoma (TCC) of the urothelium and to relate the activity of this combination to the mutational status of p53. Methods. In the Phase I portion, paclitaxel 200 mg/m2 (3-hour infusion), carboplatin dosed to an area under the curve (AUC) of 6 mg/mL . min, and methotrexate 10 mg/m2, increasing in 10-mg/m2 increments, were administered on day 1 and every 21 days thereafter with granulocyte colony-stimulating factor (G-CSF) and leucovorin support. Subsequently, a Phase II study was initiated in which the carboplatin dose was lowered to an AUC of 5 to allow treatment without G-CSF. p53 expression was evaluated using immunohistochemistry. Results. Thirty-three patients were accrued. Median age was 66 years. No dose-limiting toxicities were seen in the Phase I portion despite escalation of the methotrexate to 60 mg/m2. Principal toxicities were myelosuppression and neuropathy. The overall response rate (Phase I and II) was 56% (95% confidence interval 38% to 74%). Median survival was 15.5 months; 88% of patients overexpressed p53 at the primary site. Conclusions. Paclitaxel, carboplatin, and methotrexate were well tolerated and active in advanced TCC. The high response rate to this regimen despite frequent p53 mutation is consistent with the p53-independent mechanism of paclitaxel. Whether this regimen is superior to methotrexate/vinblastine/doxorubicin/cisplatin, other paclitaxel-based regimens, or to paclitaxel alone will require comparative trials. Copyright (C) 2000 Elsevier Science Inc.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 521-525 |
| Number of pages | 5 |
| Journal | Urology |
| Volume | 55 |
| Issue number | 4 |
| DOIs | |
| State | Published - Apr 2000 |
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ASJC Scopus subject areas
- Urology
Cite this
Phase I/II study of paclitaxel, carboplatin, and methotrexate in advanced transitional cell carcinoma : A well-tolerated regimen with activity independent of p53 mutation. / Edelman, Martin J.; Meyers, Frederick J; Miller, Tim R.; Williams, Stephen G.; Gandour-Edwards, Regina F; deVere White, Ralph W.
In: Urology, Vol. 55, No. 4, 04.2000, p. 521-525.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Phase I/II study of paclitaxel, carboplatin, and methotrexate in advanced transitional cell carcinoma
T2 - A well-tolerated regimen with activity independent of p53 mutation
AU - Edelman, Martin J.
AU - Meyers, Frederick J
AU - Miller, Tim R.
AU - Williams, Stephen G.
AU - Gandour-Edwards, Regina F
AU - deVere White, Ralph W
PY - 2000/4
Y1 - 2000/4
N2 - Objectives. To evaluate the feasibility and activity of paclitaxel, carboplatin, and methotrexate in advanced transitional cell carcinoma (TCC) of the urothelium and to relate the activity of this combination to the mutational status of p53. Methods. In the Phase I portion, paclitaxel 200 mg/m2 (3-hour infusion), carboplatin dosed to an area under the curve (AUC) of 6 mg/mL . min, and methotrexate 10 mg/m2, increasing in 10-mg/m2 increments, were administered on day 1 and every 21 days thereafter with granulocyte colony-stimulating factor (G-CSF) and leucovorin support. Subsequently, a Phase II study was initiated in which the carboplatin dose was lowered to an AUC of 5 to allow treatment without G-CSF. p53 expression was evaluated using immunohistochemistry. Results. Thirty-three patients were accrued. Median age was 66 years. No dose-limiting toxicities were seen in the Phase I portion despite escalation of the methotrexate to 60 mg/m2. Principal toxicities were myelosuppression and neuropathy. The overall response rate (Phase I and II) was 56% (95% confidence interval 38% to 74%). Median survival was 15.5 months; 88% of patients overexpressed p53 at the primary site. Conclusions. Paclitaxel, carboplatin, and methotrexate were well tolerated and active in advanced TCC. The high response rate to this regimen despite frequent p53 mutation is consistent with the p53-independent mechanism of paclitaxel. Whether this regimen is superior to methotrexate/vinblastine/doxorubicin/cisplatin, other paclitaxel-based regimens, or to paclitaxel alone will require comparative trials. Copyright (C) 2000 Elsevier Science Inc.
AB - Objectives. To evaluate the feasibility and activity of paclitaxel, carboplatin, and methotrexate in advanced transitional cell carcinoma (TCC) of the urothelium and to relate the activity of this combination to the mutational status of p53. Methods. In the Phase I portion, paclitaxel 200 mg/m2 (3-hour infusion), carboplatin dosed to an area under the curve (AUC) of 6 mg/mL . min, and methotrexate 10 mg/m2, increasing in 10-mg/m2 increments, were administered on day 1 and every 21 days thereafter with granulocyte colony-stimulating factor (G-CSF) and leucovorin support. Subsequently, a Phase II study was initiated in which the carboplatin dose was lowered to an AUC of 5 to allow treatment without G-CSF. p53 expression was evaluated using immunohistochemistry. Results. Thirty-three patients were accrued. Median age was 66 years. No dose-limiting toxicities were seen in the Phase I portion despite escalation of the methotrexate to 60 mg/m2. Principal toxicities were myelosuppression and neuropathy. The overall response rate (Phase I and II) was 56% (95% confidence interval 38% to 74%). Median survival was 15.5 months; 88% of patients overexpressed p53 at the primary site. Conclusions. Paclitaxel, carboplatin, and methotrexate were well tolerated and active in advanced TCC. The high response rate to this regimen despite frequent p53 mutation is consistent with the p53-independent mechanism of paclitaxel. Whether this regimen is superior to methotrexate/vinblastine/doxorubicin/cisplatin, other paclitaxel-based regimens, or to paclitaxel alone will require comparative trials. Copyright (C) 2000 Elsevier Science Inc.
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U2 - 10.1016/S0090-4295(99)00538-5
DO - 10.1016/S0090-4295(99)00538-5
M3 - Article
VL - 55
SP - 521
EP - 525
JO - Urology
JF - Urology
SN - 1527-9995
IS - 4
ER -