Phase II trial of dose-dense doxorubicin plus gemcitabine followed by paclitaxel plus carboplatin in patients with advanced urothelial carcinoma and impaired renal function Journal Article

  

Authors:	Galsky, M. D.; Iasonos, A.; Mironov, S.; Scattergood, J.; Boyle, M. G.; Bajorin, D. F.
Article Title:	Phase II trial of dose-dense doxorubicin plus gemcitabine followed by paclitaxel plus carboplatin in patients with advanced urothelial carcinoma and impaired renal function
Abstract:	BACKGROUND. Cisplatin-based therapy is standard in patients with advanced urothelial carcinoma but a large proportion are ineligible due to renal impairment. The safety and activity of a dose-dense carboplatin-based regimen in this patient population were explored. METHODS. Patients with advanced urothelial carcinoma who were ineligible for cisplatin were eligible based on at least 1 of the following: 1) serum creatinine > 1.5 mg/dL; 2) creatinine clearance of >30 mL/min/1.73 m2 and <60 mL/min/1.73 m 2; and/or 3) prior nephrectomy. Patients received treatment with doxorubicin plus gemcitabine every other week × 5 cycles followed by paclitaxel plus carboplatin weekly × 12 cycles. RESULTS. Twenty-five patients were treated. Myelosuppression was the major toxicity, with 28% of patients experiencing grade 3-4 neutropenia; there were only 2 (8%) episodes of febrile neutropenia. Grade ≥3 nonhematologic toxicities were infrequent with the exception of grade ≥3 thrombotic episodes in 4 (16%) patients. There were 5 complete responses and 9 partial responses for an overall response rate of 56% (95% confidence interval [CI]: 35%-76%). The median survival was 15 months (95% CI: 11-30). At a median follow-up for survivors of 45 months, 7 (28%) patients are disease-free. CONCLUSIONS. Dose-dense sequential chemotherapy is tolerable and active in patients with urothelial carcinoma and renal impairment. Prolonged disease-free survival is achievable in a subset of patients with primary unresectable disease or lymph-node only metastases treated with carboplatin-based therapy ± surgical consolidation. Randomized trials are needed to define the optimal regimen in patients with advanced urothelial carcinoma and renal impairment. © 2007 American Cancer Society.
Keywords:	adult; cancer survival; clinical article; treatment outcome; treatment response; aged; disease-free survival; middle aged; survival rate; clinical trial; drug tolerability; fatigue; neutropenia; doxorubicin; advanced cancer; cancer combination chemotherapy; diarrhea; dose response; drug dose reduction; drug safety; drug withdrawal; side effect; gemcitabine; paclitaxel; cancer patient; disease free survival; chemotherapy; follow up; lymph node metastasis; anorexia; carboplatin; multiple cycle treatment; phase 2 clinical trial; cohort studies; anemia; bone marrow suppression; blood toxicity; nausea; neuropathy; stomatitis; thrombocytopenia; vomiting; antineoplastic combined chemotherapy protocols; dehydration; combination chemotherapy; creatinine; creatinine blood level; antineoplastic activity; continuous infusion; dose-response relationship, drug; bladder cancer; urinary bladder neoplasms; nephrectomy; alanine aminotransferase blood level; dyspnea; febrile neutropenia; rash; alanine aminotransferase; disease severity; cardiotoxicity; thrombosis; urothelial carcinoma; inoperable cancer; maximum tolerated dose; dyspepsia; deoxycytidine; urinary tract carcinoma; creatinine clearance; dose-dense; kidney dysfunction; renal impairment; kidney diseases
Journal Title:	Cancer
Volume:	109
Issue:	3
ISSN:	0008-543X
Publisher:	Wiley Blackwell
Date Published:	2007-02-01
Start Page:	549
End Page:	555
Language:	English
DOI:	10.1002/cncr.22454
PUBMED:	17200962
PROVIDER:	scopus
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-33846665540&partnerID=40&md5=ece7366b6ef43ddcd40db62f4c406918
Notes:	--- - "Cited By (since 1996): 14" - "Export Date: 17 November 2011" - "CODEN: CANCA" - "Source: Scopus"

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