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© 2001 American Society for Clinical Oncology Paclitaxel and Gemcitabine Chemotherapy for Advanced Transitional-Cell Carcinoma of the Urothelial Tract: A Phase II Trial of the Minnie Pearl Cancer Research NetworkFrom the Sarah Cannon Cancer Center, Nashville, TN; Tennessee Oncology, Professional Limited Liability Corporation, Grand Rapids Community Clinical Oncology Program, Grand Rapids, MI; Mid-Florida Hematology & Oncology Centers, Professional Association, Orange City, FL; and Atlanta Cancer Care, Atlanta, GA. Address reprint requests to Anthony A. Meluch, MD, The Sarah Cannon Cancer Center, 250 25th Ave North, Ste 412, Nashville, TN 37203; email: ameluch{at}tnonc.com
PURPOSE: To evaluate the toxicity and efficacy of combination chemotherapy with paclitaxel and gemcitabine in patients with advanced transitional-cell carcinoma of the urothelial tract. PATIENTS AND METHODS: Fifty-four patients with advanced unresectable urothelial carcinoma entered this multi-centered, community-based, phase II trial between May 1997 and December 1999. All patients were treated with paclitaxel 200 mg/m2 by 1-hour intravenous (IV) infusion on day 1 and gemcitabine 1,000 mg/m2 IV on days 1, 8, and 15; courses were repeated every 21 days. Patients who had objective response or stable disease continued treatment for six courses. RESULTS: Twenty-nine of 54 patients (54%; 95% confidence interval, 40% to 67%) had major responses to treatment, including 7% complete responses. With a median follow-up of 24 months, 16 patients (30%) remain alive and nine (17%) are progression-free. The median survival for the entire group was 14.4 months; 1- and 2-year actuarial survival rates were 57% and 25%, respectively. Seven (47%) of 15 patients previously treated with platinum-based chemotherapy responded to paclitaxel/gemcitabine. Grade 3/4 toxicity was primarily hematologic, including leukopenia (46%), thrombocytopenia (13%), and anemia (28%). Ten patients (19%) required hospitalization for neutropenia and fever, and one patient had treatment-related septic death. CONCLUSION: The combination of paclitaxel and gemcitabine is active and well tolerated in the first- or second-line treatment of patients with advanced transitional-cell carcinoma of the urothelial tract. Response rate and duration compare favorably with those produced by other active, first-line regimens. This regimen should be further evaluated in phase II and III studies, as well as in patients with compromised renal function.
IN THE YEAR 2001, IT is estimated that over 55,000 cases of transitional-cell carcinoma (TCC) of the urothelial tract were diagnosed in the United States.1 Although many of these patients have localized disease at diagnosis, nearly two thirds of those with muscle invasion will subsequently develop regional or systemic recurrence. The prognosis for patients with metastatic TCC of the urothelial tract remains poor, with median survival of approximately 12 months. However, this disease is somewhat more responsive to chemotherapy than many other epithelial malignancies, and current regimens can produce high response rates and lengthen survival. Historically, the most active single agents have been cisplatin and methotrexate, although published single-agent response rates have varied from 12% to 35%.2,3 The subsequent development of combination chemotherapy regimens centered around these two agents and was highlighted by a 72% response rate demonstrated with the combination of methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC).4 Until recently, the M-VAC regimen has been considered the standard regimen for advanced TCC, and it has demonstrated superiority to single-agent cisplatin and to the combination of cyclophosphamide, doxorubicin, and cisplatin in randomized trials.3,5-11 Unfortunately, the therapeutic results with M-VAC in these larger trials were inferior to those reported in initial phase II trials, with lower response rates, fewer complete responses, and median survivals of 10 to 13 months. Long-term follow-up in two large trials has documented progression-free survival rates of only 2% and 3.7%, at 5 and 6 years, respectively.3,6 In addition, the M-VAC regimen has been associated with considerable toxicity, including myelosuppression, mucositis, nephrotoxicity, and neuropathy. Therapy-related mortality ranges from 2% to 4%.3,10,11 Because of its toxicity, the M-VAC regimen is frequently not appropriate for treatment of patients who are elderly, have renal insufficiency, or have other coexistent medical problems. Therefore, the development of more active and less toxic treatment for advanced TCC is necessary. Paclitaxel and gemcitabine are two of the new antineoplastic agents that have demonstrated activity against advanced TCC. In a phase II trial conducted by the Eastern Cooperative Oncology Group, paclitaxel (250 mg/m2 administered as a 24-hour intravenous [IV] infusion every 3 weeks) produced a 42% response rate in 26 chemotherapy-naïve patients with advanced TCC.12 In a smaller study of nine previously untreated patients who had renal insufficiency, paclitaxel administered as a 24-hour infusion demonstrated a 56% response rate.13 A third study of single-agent paclitaxel in patients with advanced TCC who were refractory to prior chemotherapy yielded a lesser response rate of 7%.14 The activity of gemcitabine in advanced TCC was first demonstrated in a phase I trial in which four (27%) of 15 patients previously treated with M-VAC responded.15 Gemcitabine doses ranged from 875 mg/m2 to 1,307 mg/m2 administered on days 1, 8, and 15 of a 28-day cycle. Three subsequent phase II trials, all using a gemcitabine dose of 1,200 mg/m2 on days 1, 8, and 15 of a 4-week cycle, demonstrated response rates ranging from 23% to 28%.16-18 Single-agent therapy with paclitaxel and gemcitabine was well tolerated in these phase I and II studies. Recently, combination regimens containing paclitaxel and gemcitabine, with or without other agents, have proven effective and well tolerated in the treatment of non–small-cell lung cancer.19 In an effort to assess the efficacy and toxicity of the combination of these two agents in patients with advanced TCC, we initiated a trial of this novel regimen. We now describe the results of this multicenter phase II trial of paclitaxel/gemcitabine performed in The Minnie Pearl Cancer Research Network.
Eligible patients had histologically confirmed TCC of the urothelial tract that was either metastatic or locally advanced and unresectable. Patients were required to have measurable disease defined by radiographs, computed tomography, or cystoscopy. Patients may have had previous intravesical therapy as long as it was administered more than 1 month before study enrollment. Similarly, radiation therapy was allowed as long as: (1) the course was completed more than 4 weeks before enrollment, (2) less than 25% of marrow-bearing areas were included, and (3) previous radiation therapy had not been delivered to index lesions being used for tumor-response assessment. A maximum of one prior systemic chemotherapy regimen, not containing either paclitaxel or gemcitabine, was acceptable. Additional requirements included an Eastern Cooperative Oncology Group performance status of  2, WBC of  3,500/µL, platelet count of 100,000/µL, serum bilirubin of 1.5 mg/dL, and serum creatinine of 1.5 mg/dL (or glomerular filtration rate, calculated or measured, 60 mL/min). All patients gave written informed consent before entering this clinical trial. The study was approved by the institutional review board at Centennial Medical Center and the review boards of participating network sites. All patients received paclitaxel 200 mg/m2 administered by 1-hour IV infusion on day 1 and gemcitabine 1,000 mg/m2 administered by 30-minute IV infusion on days 1, 8, and 15. Treatment courses were repeated every 21 days. Premedications for paclitaxel included dexamethasone (20 mg taken orally 12 and 4 hours before each dose), as well as diphenhydramine (50 mg IV), cimetidine (300 mg IV), and dexamethasone (20 mg IV given 30 minutes before paclitaxel administration). Cytokines were not routinely used. All patients received full doses of both drugs on the first day of treatment. Subsequent dose modifications were based on hematologic and nonhematologic toxicity. On days 8 and 15 of each cycle, full-dose gemcitabine was given if the patient had a WBC of more than 3,000/µL and a platelet count of more than 75,000/µL. For a patient with a WBC of 2,000/µL to 3,000/µL, a 75% dose of gemcitabine was administered, and if the WBC was less than 2,000/µL, the gemcitabine dose was omitted. On the first day of each course, full doses of both drugs were administered if the WBC was more than 3,000/µL and the platelet count was more than 100,000/µL. If counts were below these levels, treatment was delayed for 1 week and then administered at the previous dose levels if the counts had increased to above these levels. Any patient requiring hospitalization for neutropenia and fever received 75% doses of paclitaxel and gemcitabine during all subsequent courses. Patients who developed reversible grade 3 or 4 nonhematologic toxicity had treatment held for 1 week or until the toxicity improved to less than grade 2, and then received 75% doses of the offending agent(s) during subsequent courses. Any patient who developed a severe acute hypersensitivity reaction (grade 3 or 4) to either agent had the agent discontinued. Patients with irreversible grade 3 or 4 nonhematologic toxicity were removed from the study. There were no dose escalations planned. Further local therapy (resection or radiation therapy) was allowed in patients with locally advanced disease after assessment of response to paclitaxel/gemcitabine. All patients were evaluated for response after completing two courses of therapy; patients with objective response or stable disease continued treatment for a maximum of six courses of therapy. Patients were reassessed for response after each two courses of treatment. All patients were assigned a response category based on their best response to chemotherapy.
All patients were assigned a response category based on standard definitions. Complete response required the total disappearance of clinically and radiographically detectable disease for at least 4 weeks. Partial response required a The primary objectives of this phase II trial were to evaluate the feasibility and toxicity of this novel regimen in patients with advanced bladder cancer, as well as to obtain preliminary efficacy data. Since two distinct patient groups (ie, first-line and previously treated) were eligible, the target number of 50 patients was somewhat larger than the usual phase II trial. Originally we anticipated that approximately one half of patients would be previously treated. Anticipated response rates using standard regimens in first-line and second-line therapy were 45% to 50% and 15% to 20%, respectively. Substantial improvement in the response rate of either group, using the novel regimen, would indicate that further development of the regimen was indicated. Response duration, progression-free survival rate, and overall survival rate were calculated from the first day of treatment until the date of progression or death. Actuarial survival rate curves were constructed using the method of Kaplan and Meier.20 Any patient who was initiated on chemotherapy was assessable for response. Patients who received at least one dose of paclitaxel and gemcitabine were assessable for toxicity. All patients entering the trial were included in the survival determinations.
Patient Characteristics Between May 1997 and December 1999, 54 patients entered this phase II trial. The clinical characteristics of all patients are listed in Table 1. Fifteen patients had received prior chemotherapy, all with platinum-based regimens. The majority of patients (89%) had metastatic disease, and 59% had one or more visceral sites of metastasis. Fourteen patients (26%) were treated at the Sarah Cannon Cancer Center, and 40 (74%) were treated at participating network sites (see Appendix).
Treatment Received Forty-eight patients (89%) received at least two courses of treatment and were evaluated for response. Two of the six patients who received less than two cycles were withdrawn from treatment due to rapid tumor progression and were clearly nonresponders. The other four patients who received less than two cycles were removed from study for the following reasons: treatment-related death (one patient), severe hypersensitivity reaction (one patient), and patient request after an episode of neutropenia/fever (two patients). Although not reevaluated for response, all of these patients are considered nonresponders. The median number of treatment courses received was four (range, one to six). Responding patients received a median of six courses. High percentages of the planned paclitaxel and gemcitabine doses were administered on day 1 of each cycle (94% and 95%, respectively). The percentages of the planned day 8 and 15 gemcitabine doses actually administered were 82% and 61%, respectively. Most of the doses omitted or reduced were due to myelosuppression. Seven patients with locally advanced disease received radiation therapy to the pelvis after responding to paclitaxel/gemcitabine.
Treatment Efficacy All 15 patients who had received previous chemotherapy had received either M-VAC (13 patients) or carboplatin/methotrexate/vinblastine (two patients). Three of 10 patients who had previously received chemotherapy for metastatic disease had responses to paclitaxel/gemcitabine. All three responding patients had received treatment within 6 months; one patient had a complete response to paclitaxel/gemcitabine that persisted after 30 months. Two of three patients who had received neoadjuvant M-VAC responded to paclitaxel/gemcitabine. One of these patients had relapsed 8 months after completion of primary therapy and progressed on gallium nitrate before entering this trial. Both patients who had received previous adjuvant M-VAC (interval > 18 months) responded to paclitaxel/gemcitabine. Response rates in other patient subgroups are detailed in Table 2. There were no significant differences in response rates based on sex, stage, or disease location (soft tissue v visceral). Only one (17%) of six patients with poor performance status responded. Response rates were similar in patients with soft tissue metastases or locally advanced disease when compared to patients with visceral metastases (59% v 50%, respectively).
After a median follow-up of 24 months, 16 patients (30%) remain alive and nine are progression-free. The median survival of all patients was 14.4 months (range, 1 to 35+ months); actuarial 1- and 2-year survival rates were 57% and 25%, respectively (Fig 1). Median progression-free survival for patients with objective response was 9 months (range, 3 to 26 months). Three of four complete responders have progressed after response durations of 13, 28, and 34 months. Duration of response was similar in previously untreated versus treated patients (median, 9 months v 7.5 months, respectively).
Toxicity Myelosuppression, predominantly neutropenia, was the most common serious (grade 3 or 4) toxicity (Table 3). Twenty-five patients (46%) experienced grade 3/4 leukopenia (20% of courses), necessitating 11 hospitalizations for treatment of neutropenia and fever. Grade 3/4 thrombocytopenia occurred in seven patients (13%); however, no bleeding episodes occurred and only two patients required platelet transfusions. Fifteen patients (28%) developed grade 3 anemia and required RBC transfusions; 17% of the patients also received erythropoietin at some point during their therapy.
Severe nonhematologic toxicity was uncommon with this treatment regimen (Table 3). Six patients (11%) experienced severe treatment-related fatigue; other nonhematologic toxicities occurred in less than 10% of patients. Two patients had hypersensitivity reactions to paclitaxel; one was removed from the study and the other was retreated without sequelae. One patient developed bilateral pneumonitis attributed to gemcitabine, which resolved with corticosteroid therapy. There was one therapy-related death (2%) due to sepsis.
Treatment with combination chemotherapy has made a moderate impact in the management of patients with advanced bladder cancer. The M-VAC regimen has been best studied and is considered a standard regimen. This regimen has been proven superior to supportive care and is also superior to single-agent cisplatin and to the combination of cyclophosphamide/doxorubicin/cisplatin.3,11 However, the complete response rate in multicenter trials has been low, and less than 4% of patients remain disease-free after 5 years.3-7,11 Attempts to improve the M-VAC regimen by augmenting doses, in conjunction with cytokine support, have been unsuccessful.21,22 In addition, the M-VAC regimen has substantial toxicity and is not feasible in patients with compromised renal function due to the inclusion of cisplatin and methotrexate. Therefore, regimens with increased efficacy and reduced toxicity are required before further improvement can be made in the therapy of advanced bladder cancer. In the phase II trial reported here, we document the feasibility and efficacy of a combination of paclitaxel and gemcitabine in the treatment of advanced bladder cancer. This regimen produced an overall response rate of 54% and was well tolerated by most patients. The response rate in patients with visceral metastases was similar to the response rate in patients with regional extension of tumor or metastases in lymph nodes (50% and 59%, respectively). Although the majority of patients in this trial were previously untreated, the regimen was also active in the small number of patients who had previously received platinum-based chemotherapy regimens (47% response rate in this group). Although further follow-up is necessary, the median survival of 14.4 months, as well as the actuarial 1- and 2-year survival rates of 57% and 25%, respectively, compare favorably to those achieved with standard cisplatin-based combination regimens. The most frequent toxicity associated with this combination of paclitaxel and gemcitabine was myelosuppression. Twenty-five patients (46%) experienced at least one episode of grade 3 or 4 leukopenia, and there were 11 hospitalizations for treatment of neutropenia and fever. Since the patients treated in this trial were heterogeneous, with 35% having received previous chemotherapy or radiation therapy, comparison of the severity of myelosuppression versus first-line M-VAC is difficult. However, the weekly dosing schedule allowed for dose modifications to deal with myelosuppression, and hospitalization for treatment of fever and neutropenia was necessary with only 11 (5%) of 226 courses. It is possible that routine use of cytokines would have decreased the number of hospitalizations; however, most patients did not require cytokines, and we prefer to limit the expense and complexity of the regimen by making dose reductions rather than adding cytokines. Omission of the day 15 dose of gemcitabine may also have been successful in decreasing myelosuppression. In this trial, the day 15 gemcitabine dose was omitted in 31% of courses, almost always due to myelosuppression. In addition, delays in beginning the subsequent course occurred in 11% of courses, again related almost exclusively to myelosuppression. The elimination of the day 15 dose may therefore minimize myelosuppression, enable more courses to start on schedule, and allow patients to have a "break" from treatment every third week. A number of recent phase II trials have evaluated paclitaxel and gemcitabine in various combination regimens for the treatment of bladder cancer (Table 4). Substantial activity has been demonstrated when either paclitaxel or gemcitabine is combined with a platinum agent.23-31 In addition, the first completed randomized trial showed gemcitabine/cisplatin to have equivalent efficacy and decreased toxicity when compared to M-VAC.32 Triple-drug regimens containing paclitaxel, gemcitabine, and a platinum agent are also highly active33,34; however, the relative efficacy of these regimens containing new agents plus platinum remains to be determined.
Other than the results reported here, limited data are currently available regarding the combination of paclitaxel/gemcitabine in the treatment of advanced bladder cancer.35,36 In a preliminary report, paclitaxel/gemcitabine administered once every 2 weeks produced responses in eight of 15 patients who had received previous cisplatin-containing chemotherapy.36 No information was provided regarding the interval between previous treatment and paclitaxel/gemcitabine therapy. In a second report, paclitaxel/gemcitabine given every 2 weeks produced an overall response rate of 29%, but none of the six previously treated patients responded.35 At present, it seems likely that further development of new regimens for advanced bladder cancer will result in additional improvements, either by increasing efficacy or further decreasing toxicity. The continued presence of cisplatin increases the overall toxicity of treatment and limits the applicability of treatment for patients with renal insufficiency. The activity observed with paclitaxel/gemcitabine in previously treated patients requires confirmation in larger numbers of patients but suggests an immediate role for this regimen in this patient subgroup. Further investigation of this regimen in patients with renal insufficiency is also indicated. Although the first-line efficacy of paclitaxel/gemcitabine observed in this small trial compares favorably with results using M-VAC, gemcitabine/cisplatin, or other cisplatin-containing regimens, definitive phase III trials will be required to establish its role in this setting.
Tennessee Oncology, Professional Limited Liability Corporation, Nashville, TN; Comprehensive Cancer Institute, Huntsville; Montgomery Cancer Center, Montgomery; Northeast Alabama Regional Medical Center, Anniston, AL; Mid-Florida Hematology and Oncology Centers, Professional Association, Orange City; Miami Mercy Hospital, Miami, FL; Atlanta Cancer Care, Atlanta; Northwest Georgia Oncology Centers, Marietta; Phoebe Cancer Center, Albany, GA; Consultants in Blood Disorder and Cancer, Louisville; Oncology Associates of Western Kentucky, Paducah, KY; Louisiana Oncology Associates, Lafayette; Terrebonne General Medical Center, Houma; Hematology and Oncology Services, New Orleans, LA; Grand Rapids Community Clinical Oncology Program, Grand Rapids, MI; Upstate Carolina Community Clinical Oncology Program, Spartanburg, SC; Jackson Oncology, Jackson; Hattiesburg Clinic, Hattiesburg, MS; and Oncology and Hematology of Southwest Virginia, Salem, VA.
Supported in part by grants from Bristol-Myers Squibb, Princeton, NJ; Eli Lilly, Indianapolis, IN; and the Minnie Pearl Cancer Research Foundation, Nashville, TN.
1. Greenlee RT, Murray T, Bolden S, et al: Cancer statistics, 2000. Cancer 50: 7-33, 2000 2. Roth BJ: Chemotherapy for advanced bladder cancer. Semin Oncol 5: 633-634, 1996
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Saxman SB, Propert KJ, Einhorn LH, et al: Long-term follow-up of a phase III intergroup study of cisplatin alone or in combination with methotrexate, vinblastine, and doxorubicin in patients with metastatic urothelial carcinoma: A cooperative group study. J Clin Oncol 15: 2564-2569, 1997 4. Sternberg CN, Yagoda A, Scher HI, et al: Methotrexate, vinblastine, doxorubicin, and cisplatin for advanced transitional cell carcinoma of the urothelium. Cancer 64: 2448-2458, 1989[Medline] 5. Tannock I, Gospodarowicz M, Connolly J, et al: M-VAC (methotrexate, vinblastine, doxorubicin and cisplatin) chemotherapy for transitional cell carcinoma: The Princess Margaret Hospital experience. J Urol 142: 289-292, 1989[Medline] 6. Igawa M, Ohkuchi T, Ueki T, et al: Usefulness and limitations for methotrexate, vinblastine, doxorubicin, and cisplatin for the treatment of advanced urothelial cancer. J Urol 144: 662-665, 1990[Medline] 7. Conner AP, Olsson CA, Benson MC, et al: Long-term follow-up in patients treated with methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) for transitional cell carcinoma of the urinary bladder: Cause for concern. Urology 34: 353-356, 1989[Medline] 8. Boutan-Laroze A, Mahjoubi M, Droz JP, et al: M-VAC (methotrexate, vinblastine, doxorubicin, and cisplatin) for advanced carcinoma of the bladder. Eur J Cancer 27: 1690-1694, 1991 9. Sternberg CN, de Mulder P, Fossa S, et al: Interim toxicity analysis of a randomized trial in advanced urothelial tract tumors of high dose intensity M-VAC chemotherapy (HD), M-VAC (and recombinant human granulocyte colony stimulating factors) G-CSF versus classic M-VAC chemotherapy (EORTC 30924). Proc Am Soc Clin Oncol 16: 320a, 1997 (abstr 1140) 10. Loehrer P, Einhorn LH, Elson PJ, et al: A randomized comparison of cisplatin alone or in combination with methotrexate, vinblastine, and doxorubicin in patients with metastatic urothelial carcinoma of the colon: A cooperative group study. J Clin Oncol 10: 1066-1073, 1992[Abstract] 11. Logothetis CJ, Dexeus FH, Finn L, et al: A prospective randomized trial comparing M-VAC and CISCA chemotherapy for patients with metastatic urothelial tumors. J Clin Oncol 8: 1050-1055, 1990[Abstract]
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21.
Logothetis CL, Dexeus FH, Sella A, et al: Escalated therapy for refractory urothelial tumors: Methotrexate-vinblastine-doxorubicin-cisplatin plus ongoing unglycosylated recombinant human granulocyte-macrophage colony-stimulating factor. J Natl Cancer Inst 82: 667-672, 1990 22. Sternberg CN, deMulder PH, Schornagel J, et al: Randomized phase III trial in advanced urothelial tract tumors of high dose intensity M-VAC chemotherapy and G-CSF versus classic M-VAC. Proc Am Soc Clin Oncol 19: 329a, 2000 (abstr 1292) 23. Murphy BA, Johnson DR, Smith J, et al: A phase II trial of paclitaxel (P) and cisplatin (C) in metastatic transitional cell carcinoma. Proc Am Soc Clin Oncol 15: 245, 1996 (abstr 617) 24. Burch PA, Richardson RL, Cha SS, et al: A phase II trial of combination paclitaxel and cisplatin in advanced urothelial carcinoma (UC). Proc Am Soc Clin Oncol 18: 329a, 1999 (abstr 1266) 25. Vaughn DJ, Dreicer R, Manola J, et al: E2896: Paclitaxel (P)/Carboplatin (C) in advanced urothelial carcinoma and renal insufficiency: Phase II trial of the Eastern Cooperative Oncology Group (ECOG). Proc Am Soc Clin Oncol 19: 343a, 2000 (abstr 1315) 26. Redman BJ, Smith DC, Flaherty L, et al: A phase II trial of paclitaxel and carboplatin in the treatment of advanced urothelial carcinoma. J Clin Oncol 16: 1844-1848, 1998[Abstract]
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Small EJ, Lew D, Redman B, et al: Southwest Oncology Group Study of paclitaxel and carboplatin for advanced transitional-cell carcinoma: The importance of survival as a clinical trial end point. J Clin Oncol 18: 2537-2544, 2000 28. Garcia del Muro X, Marcuello E, Guma R, et al: Phase II study of docetaxel (D) and cisplatin (CDDP) in advanced urothelial cancer: Preliminary results. Proc Am Soc Clin Oncol 19: 345a, 2000 (abstr 1356)
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Moore MJ, Winquist EW, Murray N, et al: Gemcitabine plus cisplatin, an active regimen in advanced urothelial cancer: A phase II trial at the National Institute of Canada Clinical Trials Group. J Clin Oncol 17: 2876-2881, 1999 30. von der Maase H, Anderson L, Crino L, et al: A phase II study of gemcitabine and cisplatin in patients with transitional cell carcinoma (TCC) of the urothelium. Proc Am Soc Clin Oncol 16: 324a, 1997 (abstr 1155) 31. Nogue M, Carles J, Arrivi A, et al: Palliative chemotherapy with gemcitabine (Gem) and carboplatin (CBDCA) in advanced transitional cell carcinoma of the urothelium (APCCU) preliminary results. Proc Am Soc Clin Oncol 19: 345a, 2000 (abstr 1359) 32. von der Maase H, Hansen SW, Roberts JT, et al: Gemcitabine and cisplatin versus methotrexate, vinblastine, doxorubicin, and cisplatin in advanced or metastatic bladder cancer: Results of a large, randomized, multinational, multicenter phase III study. J Clin Oncol 17: 3068-3077, 2000 33. Vaishampayan UN, Smith DC, Dickow B, et al: Carboplatin, paclitaxel, and gemcitabine in advanced urothelial carcinoma: Updated results. Proc Am Soc Clin Oncol 19: 341a, 2000 (abstr 1343)
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Bellmunt J, Guillem V, Paz-Ares L, et al: Phase I-II study of paclitaxel, cisplatin, and gemcitabine in advanced transitional-cell carcinoma of the urothelium. J Clin Oncol 18: 3247-3255, 2000 35. Kaufman DS, Stadler WM, Carducci MA, et al: Gemcitabine (G) and paclitaxel (P) every two weeks (GP 2W): A multicenter phase II trial in locally advanced or metastatic urothelial cancer (UC). Proc Am Soc Clin Oncol 19: 341a, 2000 (abstr 1341) 36. Marini L, Sternberg CN, Sella A, et al: A new regimen of gemcitabine and paclitaxel in previously treated patients with advanced transitional cell carcinoma. Proc Am Soc Clin Oncol 18: 346a, 1999 (abstr 1335) Submitted November 16, 2000; accepted March 21, 2001.
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Copyright © 2001 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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ABSTRACT
INTRODUCTION
