The combination of gemcitabine and carboplatin as first‐line treatment in patients with advanced urothelial carcinoma

Abstract

BACKGROUND.The toxicity of platinum-based combinations represents a common problem for patients with advanced urothelial carcinoma. The authors previously reported encouraging efficacy for the combination of carboplatin and gemcitabine in patients considered to be unfit for cisplatin-based treatment. The objective of the current multicenter Phase II study was to evaluate the safety and efficacy of the combination of gemcitabine and carboplatin as first-line treatment in unselected patients with advanced urothelial carcinoma. METHODS.Patients with previously untreated, bidimensionally measurable, inoperable or metastatic urothelial carcinoma were treated with carboplatin, area under the concentration curve of 5 (Day 1) and gemcitabine at a dose of 1000 mg/m 2 (Days 1 and 8), every 21 days for a total of 6 cycles. RESULTS.Sixty patients (49 men and 11 women, with a median age of 69 yrs) were enrolled in the current study. Intent-to-treat analysis demonstrated an objective response rate (ORR) of 38.4% (95% confidence interval [95% CI], 26 -51.8%) (11.7% complete responses and 26.7% partial responses). The median time to disease progression was 7.6 months (95% CI, 4.5-10.7 mos) and the median overall survival was 16.3 months (95% CI, 12-20.6 mos). The median survival was comparable to that reported for the combination of methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) according to the Memorial Sloan-Kettering Cancer Center prognostic model for patients with similar baseline prognostic features. Grade 3 or 4 toxicity (according to the National Cancer Institute Common Toxicity Criteria [version 2.0]) included anemia (18%), thrombocytopenia (23%), and neutropenia (52%), with 7 episodes of febrile neutropenia (11%) reported. Nonhematologic toxicity was rare. One toxic death occurred during the study. CONCLUSIONS.The combination of gemcitabine and carboplatin appears to have considerable activity as the first-line treatment of unselected patients with advanced urothelial carcinoma with manageable toxicity, and deserves further evaluation in this setting.

Predicting response of bladder cancers to gemcitabine and carboplatin neoadjuvant chemotherapy through genome-wide gene expression profiling

“…To obtain precise expression data of cancer cells, we applied a laser microbeam microdissection system to enrich as much as possible the populations of cancer cells from the biopsy specimens of 37 invasive bladder cancers in order to establish a scoring system to predict response to GC therapy. despite recent advances, approximately 50% of patients with bladder cancer who receive Gc chemotherapy show no or very poor response in terms of staging, and a large proportion of them suffer from adverse events, such as myelosuppression and/or gastrointestinal toxicity (9,10). Although certain factors have been reported to be associated with chemosensitivity or prognosis of bladder cancer patients (20)(21)(22)(23)(24), characterization of tumor features using only one or a few of these factors has failed thus far to reliably predict individual responses, indicating a need for a more accurate method for predicting response to anticancer drugs.…”

“…4C). Although a number of patients with invasive bladder cancer have received neoadjuvant chemotherapies, such as m-Vac or Gc without prediction of their responses, the response rate (complete or partial response) to either of the Gc or m-Vac therapy has been reported to be approximately 50% (7)(8)(9)(10). Since our present and previous studies indicated that positive predictive accuracies for M-VAC and GC were 87.5% (14/16; data not shown) and 100% (10/10), respectively, personalized selection of an appropriate chemotherapy with a combination of the two prediction systems would be expected to improve the response rate to the chemotherapies.…”

“…They often are not able to undergo additional treatment as their physical condition deteriorates (9,10). Hence, the development of a reliable method to predict the effectiveness of a specific therapy is critical to assign the appropriate treatment to individual patients with bladder cancer.…”

Neo/Adjuvant Therapy in Upper Tract Urothelial Carcinoma

“…An overall 5-yr survival rate of 52% and disease-free survival rate of 40.2% were achieved by a combination chemotherapy of paclitaxel and carboplatin in a rather poor-risk population (95% with >T3, 80% with grade 3 disease, 14% N+) by Bamias et al [32]. One of the important findings of this study was the ineffectiveness of sytemic adjuvant chemotherapy in prevention of intravesical tumor recurrence ( p: 0.467).…”

A comparison of nephrotoxicity between patients with a solitary-functioning kidney and those with bilateral-functioning kidneys in cisplatin-based chemotherapy for advanced urothelial carcinoma: A Japanese retrospective multi-institutional study.

“…Outcomes for cisplatin-eligible advanced UC patients treated with carboplatin-based chemotherapies, such as gemcitabine plus carboplatin, with a median overall survival of 9.0 months, were poorer than those for patients treated with cisplatin-based chemotherapies [6,7]. However, in cisplatin-ineligible advanced UC patients, the median overall survival of patients treated with carboplatin-based combination chemotherapies are reported 7.2-16.3 months [8][9][10][11], which is almost similar (i.e., around 10 months) in those treated with cisplatinbased chemotherapies, including the reduction of cisplatin [12,13] or a split dose of cisplatin regimens [14][15][16].…”