Cisplatin, Gemcitabine, and Ifosfamide As Weekly Therapy: A Feasibility and Phase II Study of Salvage Treatment for Advanced Transitional-Cell Carcinoma

2002 ◽  
Vol 20 (13) ◽  
pp. 2965-2970 ◽  
Author(s):  
Lance C. Pagliaro ◽  
Randall E. Millikan ◽  
Shi-Ming Tu ◽  
Dallas Williams ◽  
Danai Daliani ◽  
...  
Keyword(s):  
Transitional Cell Carcinoma ◽  
Cell Carcinoma ◽  
Phase Ii ◽  
Transitional Cell ◽  
Hematologic Toxicity ◽  
Nonhematologic Toxicity ◽  
Metastatic Urothelial Carcinoma ◽  
Previously Treated Patients ◽  
Previously Treated ◽  
Grade 3

PURPOSE: We investigated the feasibility, safety, and antitumor activity of weekly gemcitabine given in combination with low doses of cisplatin and ifosfamide in previously treated patients with advanced transitional-cell carcinoma (TCC) of the urothelium. PATIENTS AND METHODS: Patients with measurable, metastatic or unresectable TCC who had received one or two prior chemotherapy regimens were eligible. On a 28-day course, doses of cisplatin 30 mg/m2, gemcitabine 800 mg/m2, and ifosfamide 1 g/m2 were given on day 1 and then repeated on day 8 and day 15 unless there was dose-limiting hematologic toxicity. RESULTS: Fifty-one patients were registered; 10 patients participated in a pilot study, after which 41 patients were registered onto the phase II protocol. Forty-eight patients (94.1%) had dose-limiting hematologic toxicity on day 8 or day 15. Nonhematologic toxicity of grade 3 or greater consisted mainly of nausea and vomiting (seven patients, 13.7%) and infection (seven patients, 13.7%). Responses could be assessed in 49 of 51 eligible patients; two complete responses (4.1%) and 18 partial responses (36.7%) were observed for an overall response rate of 40.8% (exact 95% confidence interval, 27% to 56%). CONCLUSION: This regimen of cisplatin, gemcitabine, and ifosfamide is not feasible for weekly administration because of hematologic toxicity. Nevertheless, there was promising activity with only two doses per 28-day cycle. On the basis of these results, we have initiated a phase II trial of this combination given as a single dose every 14 days in patients with untreated, metastatic urothelial carcinoma.

Treatment of patients with transitional-cell carcinoma of the urothelial tract with ifosfamide, paclitaxel, and cisplatin: a phase II trial.

1998 ◽  
Vol 16 (8) ◽  
pp. 2722-2727 ◽  
Author(s):  
D F Bajorin ◽  
J A McCaffrey ◽  
S Hilton ◽  
M Mazumdar ◽  
W K Kelly ◽  
...  
Keyword(s):  
Transitional Cell Carcinoma ◽  
Cell Carcinoma ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Day Treatment ◽  
Transitional Cell ◽  
Hematologic Toxicity ◽  
Primary Tumors ◽  
Major Response ◽  
Nonhematologic Toxicity

PURPOSE A phase II trial of ifosfamide, paclitaxel, and cisplatin (ITP) was conducted in previously untreated patients with advanced transitional-cell carcinoma (TCC) to assess its efficacy and toxicity. PATIENTS AND METHODS Thirty patients with metastatic or unresectable TCC were treated with ifosfamide 1.5 g/m2/d for 3 days with paclitaxel 200 mg/m2 over 3 hours and cisplatin 70 mg/m2 on day 1 of each 28-day treatment cycle. Therapy was continued for a maximum of six cycles. Prophylactic hematopoietic growth factor (recombinant human granulocyte colony-stimulating factor [rhG-CSF]) was given on days 6 to 17 of each cycle. RESULTS Twenty-three of 29 assessable patients (79%; 95% confidence interval [CI], 60% to 92%) demonstrated a major response (six complete [CR] and 17 partial [PR]) with response durations that ranged from 5 to 24+ months. Five patients with T4 bladder primary tumors had a major response, two with pathologic CR. At a median follow-up duration of 17.9 months, nine (31%) patients remain disease-free (range, 10+ to 24+). Hematologic toxicity included anemia, thrombocytopenia, and neutropenia; febrile neutropenia was observed in 17% of patients and 4% of cycles. No grade 4 nonhematologic toxicity was observed. Grade 3 nonhematologic toxicity included alopecia, allergy (3%), renal insufficiency (13%), and neuropathy (10%). Dose reductions or drug omissions were necessary for adverse events in seven (23%) patients. CONCLUSION ITP is an active, well-tolerated regimen in previously untreated patients with TCC of the urothelial tract. Further study of this regimen in patients with both TCC and non-transitional-cell urothelial tumors is ongoing.

Weekly Paclitaxel and Gemcitabine in Advanced Transitional-Cell Carcinoma of the Urothelium: A Phase II Hoosier Oncology Group Study

2005 ◽  
Vol 23 (6) ◽  
pp. 1185-1191 ◽  
Author(s):  
Jinxing Li ◽  
Beth Juliar ◽  
Constantin Yiannoutsos ◽  
Rafat Ansari ◽  
Edward Fox ◽  
...  
Keyword(s):  
Transitional Cell Carcinoma ◽  
Cell Carcinoma ◽  
Phase Ii ◽  
Pulmonary Toxicity ◽  
Objective Response ◽  
Transitional Cell ◽  
Weekly Paclitaxel ◽  
Grade 3 ◽  
Higher Doses

PurposeTo evaluate the efficacy and toxicity of weekly paclitaxel and gemcitabine in patients with advanced transitional-cell carcinoma (TCC) of the urothelial tract.Patients and MethodsPatients with advanced unresectable TCC were enrolled onto this multicenter, community-based, phase II trial. Initially, patients were treated with paclitaxel 110 mg/m2and gemcitabine 1,000 mg/m2by intravenous infusion on days 1, 8, and 15 every 28 days. Patients who had an objective response or stable disease continued treatment for a maximum of six courses. Paclitaxel was decreased to 90 mg/m2and gemcitabine was decreased to 800 mg/m2for the last 12 patients because of a concerning incidence of pulmonary toxicity in the first 24 patients.ResultsThirty-six patients were enrolled between September 1998 and March 2003. Twenty-four patients received the higher doses of paclitaxel and gemcitabine, and 12 patients received the lower doses. Twenty-five (69.4%) of 36 patients had major responses to treatment, including 15 patients (41.7%) with complete responses. With a median follow-up time of 38.7 months, the median survival time was 15.8 months. Grade 3 and 4 toxicities included granulocytopenia (36.1%), thrombocytopenia (8.3%), and neuropathy (16.7%). Five patients (13.9%) had grades 3 to 5 pulmonary toxicity, and one patient had grade 2 pulmonary toxicity.ConclusionWeekly paclitaxel and gemcitabine is an active regimen in the treatment of patients with advanced TCC. However, because of the high incidence of pulmonary toxicity associated with this schedule of paclitaxel and gemcitabine, we recommend against the use of this regimen in this patient population.

Phase II trial of docetaxel in patients with advanced or metastatic transitional-cell carcinoma.

1997 ◽  
Vol 15 (5) ◽  
pp. 1853-1857 ◽  
Author(s):  
J A McCaffrey ◽  
S Hilton ◽  
M Mazumdar ◽  
S Sadan ◽  
W K Kelly ◽  
...  
Keyword(s):  
Transitional Cell Carcinoma ◽  
Cell Carcinoma ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Single Agent ◽  
Transitional Cell ◽  
Survival Duration ◽  
Hematologic Toxicity ◽  
Hematopoietic Growth Factors ◽  
Cutaneous Toxicity

PURPOSE A phase II trial of docetaxel was conducted to assess its efficacy and toxicity in patients with advanced transitional-cell carcinoma (TCC) who had failed to respond to prior cisplatin-based therapy. PATIENTS AND METHODS Thirty assessable patients who had failed to respond to or relapsed after one prior cisplatin-containing regimen were treated with docetaxel 100 mg/m2 over 1 hour, every 21 days. All patients were premedicated with dexamethasone and diphenhydramine to reduce allergic reactions. Reductions of subsequent doses were made for severe hematologic toxicity. Prophylactic hematopoietic growth factors were not used. RESULTS Four of 30 patients (13.3%; 95% confidence interval [CI], 3.8% to 30.7%) demonstrated a partial response (PR), with durations of response ranging from 3 to 8 months. The estimated median survival duration for all patients is 9 months (95% CI, 6 to 12 months) with a median follow-up time of 14 months (range, 1 to 27). Hematologic toxicity included anemia, thrombocytopenia, neutropenia, and febrile neutropenia. Nonhematologic toxicity included alopecia and mucositis. Fluid retention was not observed and cutaneous toxicity was mild and infrequent. Dose reductions were necessary for adverse events in 18 patients (60%). CONCLUSION Docetaxel is an active single agent in previously treated patients with TCC of the urothelial tract. Therapy was well tolerated in this patient population but myelosuppression was frequent. Further study in previously untreated patients, both alone and in combination, is warranted.

scholarly journals Phase II study of bortezomib in patients with previously treated advanced urothelial tract transitional cell carcinoma: CALGB 90207

2008 ◽  
Vol 19 (5) ◽  
pp. 946-950 ◽  
Author(s):  
J.E. Rosenberg ◽  
S. Halabi ◽  
B.L. Sanford ◽  
A.L. Himelstein ◽  
J.N. Atkins ◽  
...  
Keyword(s):  
Transitional Cell Carcinoma ◽  
Cell Carcinoma ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Transitional Cell ◽  
Previously Treated

Effective Dosing of Topotecan With Carboplatin in Relapsed Ovarian Cancer: A Phase I/II Study

2001 ◽  
Vol 19 (13) ◽  
pp. 3255-3259 ◽  
Author(s):  
A. Bowman ◽  
T. Rye ◽  
G. Ross ◽  
A. Wheatley ◽  
J. F. Smyth
Keyword(s):  
Phase I ◽  
Dose Escalation ◽  
Area Under The Curve ◽  
Maximum Tolerated Dose ◽  
Hematologic Toxicity ◽  
Nonhematologic Toxicity ◽  
Previously Treated Patients ◽  
Previously Treated ◽  
Grade 3 ◽  
Carboplatin Auc

PURPOSE: This phase I/II study was performed to evaluate the feasibility of administering the topoisomerase inhibitor topotecan in combination with carboplatin. PATIENTS AND METHODS: Topotecan was given as a 30-minute infusion daily for 5 days, with carboplatin given immediately after topotecan on day 5. Treatment was repeated every 21 days. Carboplatin and then topotecan were escalated in sequential cohorts of three to six patients. Four dosage combinations of topotecan days 1 to 5 and carboplatin (day 5) were tested: 0.5 mg/m2/d and carboplatin area under the curve (AUC) of 4, topotecan 0.5 mg/m2/d and carboplatin AUC of 5, topotecan 0.75 mg/m2/d and carboplatin AUC of 5, and topotecan 1.0 mg/m2/d and carboplatin AUC of 5. RESULTS: Grade 3 and 4 neutropenia was common at doses of 0.75 mg/m2/d and above, but dose-limiting hematologic toxicity occurred in only one patient. The most common reason for dose reduction or delay was failure of myelosuppression to resolve by day 21. Nonhematologic toxicity was generally mild. The maximum-tolerated dose as defined in the protocol was not reached, but topotecan dose escalation was stopped at 1.0 mg/m2/d, because delayed neutrophil recovery precluded re-treatment on a 21-day schedule. CONCLUSION: Hematologic toxicity was common but rarely serious, and the combination of topotecan with carboplatin on this schedule was safe and well tolerated. Giving carboplatin to patients after topotecan on day 5, rather than on day 1, allowed dose escalation beyond the levels reported in other studies. The recommended doses for previously treated patients are topotecan 0.75 mg/m2/d, days 1 to 5, with carboplatin at an area under the curve (AUC) of 5 following topotecan on day 5. The combination of topotecan 1 mg/m2/d, days 1 to 5, followed on day 5 by carboplatin at an AUC of 5, merits further examination in untreated patients.

Significant activity of paclitaxel in advanced transitional-cell carcinoma of the urothelium: a phase II trial of the Eastern Cooperative Oncology Group.

1994 ◽  
Vol 12 (11) ◽  
pp. 2264-2270 ◽  
Author(s):  
B J Roth ◽  
R Dreicer ◽  
L H Einhorn ◽  
D Neuberg ◽  
D H Johnson ◽  
...  
Keyword(s):  
Transitional Cell Carcinoma ◽  
Cell Carcinoma ◽  
Single Agent ◽  
Objective Response ◽  
Locally Advanced ◽  
Transitional Cell ◽  
Survival Duration ◽  
Hematologic Toxicity ◽  
Significant Activity ◽  
Grade 3

PURPOSE To assess the efficacy and toxicity of single-agent paclitaxel as first-line chemotherapy in patients with locally advanced or metastatic transitional-cell carcinoma of the urothelium. PATIENTS AND METHODS Twenty-six eligible patients were enrolled onto this cooperative group study and treated with paclitaxel at a dosage of 250 mg/m2 by 24-hour continuous infusion every 21 days until progression or patient intolerance. All patients received recombinant human granulocyte colony-stimulating factor (rhG-CSF) at 5 micrograms/kg/d for at least 10 days during each cycle. RESULTS Eleven of 26 patients (42%; 95% confidence interval [CI], 23% to 63%) demonstrated an objective response, with seven achieving a complete clinical response (CR) (27%; 95% CI, 12% to 48%) and four (15%) a partial response (PR). The median duration of response in the 11 responders is 7+ months (range, 4 to 17), with five responders (four CRs, one PR) remaining progression-free at 5, 6, 10, 12, and 16 months from the start of therapy. The estimated median survival duration for all patients is 8.4 months. Hematologic toxicity consisted of anemia (12% grade 3) and granulocytopenia (4% grade 3, 19% grade 4), with two patients developing granulocytopenic fevers. Nonhematologic toxicity included grade 3 mucositis in 11%, grade 3 neuropathy in 11%, and grade 4 diarrhea in 4%. CONCLUSION Single-agent paclitaxel at this dosage and schedule is one of the most active single agents in previously untreated patients with advanced urothelial carcinoma, and is well tolerated by this patient population when given with hematopoetic growth factor support.

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