A phase II study of weekly paclitaxel in elderly patients with advanced non-small cell lung cancer.

PURPOSE: Our aim was to evaluate the efficacy, toxicity, and pharmacokinetic behavior of single-agent paclitaxel given weekly to elderly patients with lung cancer. EXPERIMENTAL DESIGN: Previously untreated patients with stage IIIB/IV non-small cell lung cancer were eligible for the study if they were at least 70 years of age and had preserved organ function. Paclitaxel was administered over 1 h at a dose of 90 mg/m(2) for 6 consecutive weeks on an 8-week cycle. The pharmacokinetics of paclitaxel were assessed during the first and sixth week of therapy in a subgroup of eight patients. RESULTS: A total of 35 patients (median age, 76 years; range, 70-85) were enrolled. The overall response rate was 23%. Median time to failure was 5.2 months, whereas the median survival time was 10.3 months. Survival rates after 1 and 2 years were 45 and 22%, respectively. Grade 3/4 toxicities included neutropenia (5.8%), hyperglycemia (17.6%), neuropathy (5.8%), and infection (8.8%). Two patients died from treatment-related toxicity. There was no significant difference (P = 0.18) between the total body clearance of paclitaxel on the first (17.4 +/- 2.9 liters/h/m(2), mean +/- SD) and sixth (15.8 +/- 4.1 liters/h/m(2)) week of therapy. CONCLUSION: Paclitaxel administered as a weekly 1-h infusion at a dose of 90 mg/m(2) is a safe and effective therapy for elderly patients with advanced non-small cell lung cancer. Its pharmacokinetics in elderly patients do not appear to differ from historical data for younger patients, and there was no suggestion of a change in drug clearance after repeated weekly dosing.     

Randomized phase II trial of weekly paclitaxel combined with carboplatin versus standard paclitaxel combined with carboplatin for elderly patients with advanced non-small-cell lung cancer

BackgroundThe optimal platinum doublet regimen in elderly patients with non-small-cell lung cancer (NSCLC) is still uncertain. We conducted a randomized phase II study to compare the efficacy and safety of weekly paclitaxel combined with carboplatin with those of the standard schedule.Patients and methodsElderly patients (age ≥70 years) with advanced NSCLC were randomly assigned to either the weekly arm {70 mg/m² paclitaxel on days 1, 8, and 15 and carboplatin [area under the curve (AUC) = 6] on day 1} or the standard arm [200 mg/m² paclitaxel and carboplatin (AUC = 6) on day 1]. The primary end point was the overall response rate (ORR).ResultsEighty-two patients were enrolled. The ORR and median progression-free survival were 55% and 6.0 months for the weekly arm and 53% and 5.6 months for the standard arm. Grade 3/4 neutropenia and peripheral neuropathy were observed in 41% and 0% of the patients in the weekly arm and in 88% and 25% in the standard arm, respectively.ConclusionsThis is the first randomized study that compares the platinum doublet designed specifically for the elderly. Regarding the safety, the weekly regimen was less toxic than the standard regimen and seems to be preferable for elderly patients with advanced NSCLC.     

Phase II study of carboplatin combined with weekly docetaxel in patients with advanced non-small cell lung cancer

Purpose

This phase II study is performed to evaluate the safety, efficacy and tolerability of carboplatin combined with weekly docetaxel in patients with advanced non-small cell lung cancer (NSCLC).

Patients and methods

All patients were treated with the combination of docetaxel 35 mg/m² by IV infusion over 30–60 min weekly, on days 1, 8, and 15, for 3 weeks followed by 1 week of rest, with intravenous carboplatin (AUC 6) administered immediately afterward on day 1. Cycles were repeated every 28 days.

Results

Forty-seven (95.9%) of the 49 patients were assessable for response, one case of complete response and 17 cases of partial response were confirmed, giving an overall response rate of 36.7% (95% CI 23.2–50.2%). The median time to progression and overall survival (OS) for all patients were 5.2 months (95% CI 4.1–6.3 months) and 10.4 months (95% CI 7.3–13.5 months), respectively. The estimate of OS at 12 months was 37.6% (95% CI 24.0–51.2%). The most severe hematologic adverse event was anemia, which occurred with grade 3/4 intensity in 7 (14.9%) patients. Neutropenia occurred with grade 3 intensity in 4 (8.5%) patients. However, no grade 4 neutropenia was observed. Grade 3 nausea/vomiting, diarrhea, asthenia, nail changes, and skin reaction were observed in 6 (12.8%), 3 (6.4%), 2 (4.3%), 2 (4.3%) and 1 (2.1%) patients. Yet, no grade 4 non-hematologic toxicity was observed.

Conclusions

The combination of carboplatin with weekly docetaxel is a tolerated treatment modality with encouraging activity and survival outcome in previously untreated patients with advanced NSCLC.     

A phase II study of weekly paclitaxel and carboplatin in previously untreated patients with advanced non-small-cell lung cancer

Purpose: Both paclitaxel (P) and carboplatin (C) have a significant activity in non-small cell lung cancer (NSCLC). Weekly administration of P is active, is dose intense, and has a favorable toxicity profile. To evaluate the efficacy and toxicity of weekly P and C in advanced-stage NSCLC, we initiated this phase II study in patients with advanced NSCLC (III B with pleural effusion and stage IV). Patients and Methods: Eligible patients were treated with paclitaxel 100 mg/m² intravenously (iv) over 1 h followed by carboplatin AUC 2 iv over 30 min. This treatment was administered weekly for 3 of every 4 wk until disease progression or intolerable toxicities. Results: Of the 30 patients enrolled in the study, one patient did not meet the eligibility criteria. Of the remaining 29 patients, 6 did not complete at least two cycles of treatment and hence were not assessable for response. The overall response rate was 43.5% (10/23) (all partial responses). An additional 43.5% had stable disease. The median time to progression was 162 d and the median duration of response was 169 d. Overall survival at 1 yr on intent-to-treat analyses was 44% and median survival was 10.8 mo. We observed the following grade 3/4 toxicities: hypersensitivity to paclitaxel (13%), hypersensitivity to carboplatin (3%), neutropenia (31%), thrombocytopenia (7%); 31% experienced grade 1 neuropathy and 17% experienced grade 2 neuropathy. Conclusions: We conclude that weekly paclitaxel and carboplatin is active and very well tolerated in patients with advanced NSCLC.     

Cost-effectiveness of weekly paclitaxel for patients with advanced non-small cell lung cancer

Paclitaxel is known to be efficacious in treating non-small cell lung cancer (NSCLC). We initiated a phase II trial of weekly paclitaxel (W-PTX) therapy in advanced NSCLC, and found that W-PTX was feasible for advanced NSCLC patients. We evaluated the cost of W-PTX from receipts and compared it with a standard cisplatin-vinorelbine (VC) regimen. The aim of this study was to assess the cost of W-PTX therapy. Previously untreated patients with stage IV NSCLC and patients with stage III B/IV NSCLC after at least one previous cisplatin based regimen were eligible if they had preserved organ function for treatment. Paclitaxel was administered at a dose of 80 mg/m2 for 3 consecutive weeks on a 4-week cycle. Patients received at least 1 course of W-PTX in our hospital and then, if possible, were treated on outpatients basis. All patients receiving the VC regimen were treated in the hospital. The mean cost of W-PTX for one month was approximately 699,000 yen per inpatient and 236,000 yen per outpatient. On the other hand, the mean cost of VC for one month was approximately 816,000 yen per patient. Although the cost of W-PTX for inpatient did not differ greatly from the cost of VC, the cost of W-PTX for outpatients was significantly lower than that of VC. The findings of this study suggest that W-PTX is feasible as a cost-effective chemotherapy for patients with advanced NSCLC.     

Randomised phase II study of ASA404 combined with carboplatin and paclitaxel in previously untreated advanced non-small cell lung cancer

ASA404 (5,6-dimethylxanthenone-4-acetic acid or DMXAA) is a small-molecule tumour-vascular disrupting agent (Tumour-VDA). This randomised phase II study evaluated ASA404 plus standard therapy of carboplatin and paclitaxel in patients with histologically confirmed stage IIIb or IV non-small cell lung cancer (NSCLC) not previously treated with chemotherapy. Patients were randomised to receive ⩽6 cycles of carboplatin area under the plasma concentration–time curve 6 mg ml⁻¹ min and paclitaxel 175 mg m⁻² (CP, n=36) or standard therapy plus ASA404 1200 mg m⁻² (ASA404-CP, n=37). There was little change in the systemic exposure of either total or free carboplatin or paclitaxel on addition of ASA404. Safety profiles were similar and manageable in both groups, with most adverse effects attributed to standard therapy. Tumour response rate (31 vs 22%), median time to tumour progression (5.4 vs 4.4 months) and median survival (14.0 vs 8.8 months, hazard ratio 0.73, 95% CI 0.39, 1.38) were improved in the ASA404 combination group compared with the standard therapy group. In conclusion, this study establishes the feasibility of combining ASA404 with carboplatin and paclitaxel in patients with previously untreated, advanced NSCLC, demonstrating a manageable safety profile and lack of adverse pharmacokinetic interactions. The results indicate that there may be a benefit associated with ASA404, but this needs to be evaluated in a larger trial.     

A randomized phase II trial comparing every 3-weeks carboplatin/paclitaxel with every 3-weeks carboplatin and weekly paclitaxel in advanced non-small cell lung cancer.

BACKGROUND: The optimal schedule of taxane administration has been an area of active interest in several recent clinical trials. METHODS: To address a pure schedule question, we randomized 161 patients with advanced stage IIIB or IV non-small-cell lung cancer (NSCLC) to either paclitaxel 225 mg/m2 every 3 weeks x 4 cycles or 75 mg/m2/week x 12 (cumulative dose on each arm = 900 mg/m2). Both arms received concurrent carboplatin AUC 6 every 3 weeks x 4 cycles. RESULTS: The two arms were well-balanced in terms of known prognostic factors. The overall response rate and survival outcomes were similar on the two arms. There was significantly more grade 3/4 thrombocytopenia and grade 2-4 anemia on the weekly arm but less severe myalgias/arthralgias and alopecia. No difference in the rates of peripheral neuropathy was observed; however, patients on the every 3 weeks arm reported significantly more taxane therapy-related side-effects on the functional assessment of cancer therapy taxane subscale. CONCLUSIONS: This randomized trial exploring schedule-related issues with carboplatin/paclitaxel confirms the versatility of this regimen.     

Low-dose weekly paclitaxel as second-line treatment for advanced non-small cell lung cancer: a phase II study

PURPOSE: To assess the activity and toxicity of low-dose weekly paclitaxel in patients with non-resectable or metastatic non-small cell lung cancer (NSCLC) and who had disease recurrence or failure with previous chemotherapy. PATIENTS AND METHODS: Forty patients with NSCLC previously treated with platinum-based chemotherapy received weekly paclitaxel 80 mg/m(2) as a 1 h infusion. The median age was 63 years (range 42-77 years); 25 patients had Eastern Cooperative Oncology Group performance status (PS) 1 and 15 had PS 2. Thirty-one patients had stage IV disease and nine stage III (eight stage IIIB and one stage IIIA). RESULTS: A total of 364 weeks of treatment were administered (median 8 weeks, range 2-17 weeks). There were no episodes of grade 3 or 4 haematological toxicities. Severe non-haematological toxicity was uncommon: grade 1-2 asthenia in 50%; grade 1-2 motor neuropathy in 45% and grade 3 in 10%; grade 1-2 sensory neuropathy in 62% of patients. Alopecia was mild. The overall response rate was 37.5% (95% CI, 23.9-55): 2 CR, 13 PR, 15 SD, 8 PD, 2 NE. Median overall survival was 9.7 months (95% CI, 6.5-12.8). Median time to progression was 5.4 months (95% CI, 1.8-8.9). CONCLUSION: A low-dose weekly paclitaxel regimen had good clinical efficacy with low toxicity in this group of patients with poor prognosis. This regimen increases the therapeutic options available for second-line therapy in NSCLC patients.     

A phase II study of carboplatin and paclitaxel as first line chemotherapy in elderly patients with advanced non-small cell lung cancer (NSCLC)

INTRODUCTION: Lung cancer is the leading cause of tumour-related deaths in the elderly population but the optimal management of advanced NSCLC in older patients has not been defined to date. The present phase II study was planned to evaluate the efficacy and toxicity of the combination of carboplatin and paclitaxel in elderly patients with advanced NSCLC. PATIENTS AND METHODS: Patients (>70 years old) who had pathologically been proven to have a NSCLC and measurable lesions were treated with paclitaxel (175 mg/m2 for 3h) and carboplatin [area under the concentration-time curve (AUC=5)] on day 1 every 3 weeks. RESULTS: Forty patients were enrolled into the study. The median age was 74 years (range, 70-78 years). Approximately 85% of the patients had stage IV and 80% had a performance status (PS) of 0-1. Nine of the 40 (22.5%; 90% CI 17.6-28.1) included patients had a partial response; one patient (2.5%; 90% CI 1.7-3.2) achieved a complete response. The overall response rate was 25% (90% CI 15.3-38.6). In addition stable disease was observed in 13 patients (32.5%; 90% CI 24.3-40.7). The median survival was 7.8 months (95% confidence interval, 5.1-11.8 months). The actual 1-year survival was 18% (95% confidence interval, 12-29%). The median time to disease progression was 4.1 months (95% CI 2.8-8.5). Overall, 37.5% of patients experienced grade 3-4 neutropenia of any duration with only two patients (5%) developing neutropenic fever. Grade 3 or 4 non-haematological toxicity was uncommon apart alopecia. CONCLUSIONS: In the present phase II study the combination of paclitaxel and carboplatin has demonstrated to be active and safe in an age-selected population.     

Measurement and impact of co-morbidity in elderly patients with advanced non-small cell lung cancer treated with chemotherapy. A phase II study of weekly paclitaxel

BACKGROUND: Aging is associated with an increasing of comorbidity and at the time of lung cancer diagnosis patients present one or more other serious disease. The aim of the study is to evaluate tolerability, response and survival of weekly paclitaxel in elderly patients with advanced NSCLC and concomitant diseases. METHODS: Patients with advanced NSCLC who were poor candidates to platinum-based therapy because of age >65 years and coexistent illnesses received weekly paclitaxel over 1 hour at a dose of 80 mg/m2. Comorbidity was evaluated according to the Charlson scale, Kaplan-Feinstein index and the Cumulative Illness Rating Scale. RESULTS: A total of 57 patients (median age, 74 years; range, 65-84) were included. The overall response rate was 44%. Median survival was 7.8 months. Grade 3-4 toxicity was uncommon: neutropenia 1.8%, thrombocytopenia 1.8%, neuropathy 7%, hypersensitivity reaction 1.8%. Comorbidity indexes were useful to characterize better the population of elderly patients, but did not define a subgroup with worse prognosis. CONCLUSIONS: The low toxicity profile and efficacy of low-dose weekly paclitaxel justified its usage in this group of poor prognosis elderly patients with advanced NSCLC and comorbidities. A comorbidity index should be introduced in prospective oncological studies in the elderly to ensure compatibility.     

Phase II study of weekly paclitaxel as second-line therapy in patients with advanced non-small cell lung cancer

A growing number of patients, mainly cisplatin-pretreated, require second-line therapy for non-small cell lung cancer (NSCLC) but the optimal treatment and appropriate criteria for patient selection have not been defined yet. A second-line phase II study was conducted in cisplatin-pretreated patients with advanced NSCLC to evaluate the activity and toxicity of weekly paclitaxel. Fifty-three consecutive NSCLC patients (9 stage IIIA-B, 44 stage IV) progressing after one front line cisplatin-based chemotherapy were enrolled. Previous treatment with taxanes was not allowed. Patients with stage III were also pretreated with thoracic radiotherapy. Weekly paclitaxel was administered as 1-h infusion at a dose of 80 mg/m(2) for three weeks with one week off, for a maximum of four courses. All patients were assessable for response, toxicity and survival. A complete response was observed in one case, partial response in 7, for an overall response rate (RR) of 15%, (95% Cl = 5-25%). Stable disease (SD) was registered in 11 patients, for an overall clinical benefit (CB = RR + SD) of 36% (95% Cl = 23-49%). Toxicity was mild, with G3-4 neutropenia and thrombocytopenia in 6 and 2% of patients, respectively. Non-hematological toxicities were negligible. No significant correlation between patient or treatment-related variable and RR was observed. CB was significantly higher in patients with non-squamous histology (P = 0.03) and no progression within 4 months of first line cisplatin-based chemotherapy (P = 0.007). Median progression-free survival (PFS) was 7 months in responders and 4 months in pts with SD. PFS was significantly related to good performance status (PS) (P = 0.002) and non-squamous histology (P = 0.004). In conclusion, weekly paclitaxel has acceptable palliative activity and excellent tolerance in cisplatin-pretreated patients. Patients with PS 0-1, non-squamous histology and with no progression within 4 months of first line cisplatin-based chemotherapy seem more likely to benefit from this treatment.     

Safety evaluation of adjuvant chemotherapy by weekly paclitaxel combined with weekly carboplatin in patients with postoperative non-small cell lung cancer

Favorable results of various comparative studies have been reported in recent years regarding adjuvant chemotherapy for non-small cell lung cancer (NSCLC), resulting in an increase in the number of facilities that proactively conduct adjuvant chemotherapy in Japan. In the present study, we evaluate the tolerability of a postoperative adjuvant chemotherapy regimen conducted in our facility using paclitaxel (PTX) and carboplatin (CBDCA). Thirteen patients who received weekly PTX and CBDCA as postoperative adjuvant chemotherapy were evaluated retrospectively. PTX was administered by iv drip infusion over 1 hour at 70-80 mg/m(2), followed by CBDCA at AUC= 2 by iv drip infusion over 1 hour. This was repeated on Days 1, 8 and 15, followed by a rest on Day 22. Two to 4 cycles were conducted in each patient. Patients were admitted only the first time, and treatment was thereafter conducted on an outpatient basis. The scheduled number of cycles could be completed in all but one patient who developed interstitial pneumonia 2 days after treatment. Non-hematologic toxicities observed included peripheral neuropathy in 3 patients, nausea in 2, general fatigue in 6, stomatitis in 2, and alopecia in 11. Hematologic toxicities include leukopenia in 10, but leukopenia was not febrile, Grade 3 or more severe in any of these patients. In addition, decreases in hemoglobin and thrombopenia were observed in 10 and 2 patients, respectively, but both adverse events were mild (< Grade 3) and could be controlled on an outpatient basis in all cases. Our findings suggested that adjuvant chemotherapy using weekly PTX/weekly CBDCA for NSCLC is well tolerated and can be safely conducted on an outpatient basis.     

Phase II study of weekly carboplatin and irinotecan as first-line chemotherapy for patients with advanced non-small cell lung cancer

Purpose

Platinum-based doublet chemotherapy has a major role in the treatment of patients with advanced non-small cell lung cancer (NSCLC). The weekly fractionated administration of cisplatin for patients with NSCLC has been shown to be active. Irinotecan and carboplatin are effective against NSCLC and demonstrated synergism with non-cross-resistance in preclinical studies. We conducted a phase II study of weekly combination of carboplatin and irinotecan as first-line chemotherapy for patients with advanced NSCLC.

Methods

From March 2009 to November 2011, 24 patients who were diagnosed with inoperable or metastatic NSCLC were enrolled. Treatment consisted of carboplatin at an AUC 2.5 mg/mL/min over 30-min intravenous infusion and irinotecan 65 mg/m² over 90-min intravenous infusion on day 1 and day 8, respectively. The treatment was repeated every 3 weeks.

Results

One patient (4.2 %) achieved complete response, and seven (29.2 %) showed partial response. Overall response rate was 33.3 %, with median response duration of 4.55 months. Nine patients had stable disease, and disease control rate was 70.8 %. With median follow-up of 12.8 months, median progression-free survival was 4.5 months (95 % CI 1.8–7.2), and median overall survival was 15.5 months (95 % CI 6.9–24.1). Major toxicity was myelosuppression. Grade 3–4 neutropenia and thrombocytopenia occurred in 50 and 20.8 % of patients, respectively. Two patients experienced febrile neutropenia. Non-hematologic toxicities were generally mild. One patient suffered grade 4 diarrhea, and one treatment-related death due to pneumonia was occurred.

Conclusion

The weekly combination of carboplatin and irinotecan showed favorable activity and manageable toxicity profiles in chemo-naïve patients with advanced NSCLC. Our results suggest that this regimen can be a reasonable chemotherapeutic option for patients with advanced NSCLC.     

紫杉醇联合顺铂及长春瑞滨联合卡铂治疗老年晚期非小细胞肺癌的临床对照研究

为了探讨紫杉醇联合顺铂及长春瑞滨联合卡铂方案对老年晚期非小细胞肺癌(non-smallcelllungcancer,NSCLC)的疗效和毒副反应,选取初治晚期NSCLC65例,分别应用TP(紫杉醇 顺铂)、NE(长春瑞滨 卡铂)方案治疗。每例均完成2个周期化疗后评价疗效及毒副反应。结果两组患者近期有效率TP组为41·9%(13/31),NE组为41·2%(14/34),差异无统计学意义,P>0·05。中位生存期TP组8·1个月,NE组7·2个月,差异无统计学意义,P>0·05。两组毒副反应均以骨髓抑制、脱发及恶心呕吐为主,TP组恶心呕吐发生率为87·1%,NE组为73·5%,白细胞减少TP组为74·9%,NE组为85·3%。两组病例均无化疗相关死亡发生。初步研究结果提示,TP、NE联合方案是治疗老年晚期NSCLC有效且耐受性较好的方案。     

A phase II study of bryostatin-1 and paclitaxel in patients with advanced non-small cell lung cancer

BACKGROUND: Bryostatin-1 is a macrocyclic lactone, which exhibits pleiotropic biological effects via protein kinase C and has shown preclinical synergy with paclitaxel for enhanced tumor cell apoptosis. PATIENTS AND METHODS: Patients had stage IIIB (pleural effusion)/IV non-small cell lung cancer, measurable disease, performance status 0-2 Eastern Cooperative Oncology Group, adequate organ function, and no prior chemotherapy. Patients received dexamethasone premedication followed by paclitaxel at a dose of 90 mg/m(2) on days 1, 8, and 15 along with bryostatin-1 50 microg/m(2) on days 2, 9, and 16 every 28 days until disease progression. Correlative assays measuring serum levels of tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), and T-lymphocyte numbers were performed based on a previous study showing cytokine induction in vivo by bryostatin-1. Fifteen patients were enrolled. RESULTS: Thirty cycles of the bryostatin-1 and paclitaxel were delivered with a median of 2 per patient (range 1-4). Myalgia was the predominant non-hematologic toxicity encountered as 3 patients developed grade 4 and 1 patient developed grade 3 myalgia. Four patients were removed from the study during cycle 1 for rapid disease progression or myalgia. Eleven patients could be evaluated for response. Five patients had stable disease, two had a mixed response, and four had progressive disease. Ten patients received second-line chemotherapy after leaving the study. Median survival was 31 weeks (95% confidence interval: 5.4-49.3). Correlative data showed a trend towards decreased plasma IL-6 and TNF-alpha after each cycle of therapy presumably due to the dexamethasone premedication and/or paclitaxel. CONCLUSIONS: This drug combination showed no significant clinical response and was associated with reproducible toxicity. The predominance of myalgia in the absence of elevated serum cytokines suggests a non-inflammatory etiology of this toxicity.     

Carboplatin plus gemcitabine therapy versus carboplatin plus weekly paclitaxel therapy for advanced non-small cell lung cancer

We compared two chemotherapy regimens for advanced non small-cell lung cancer. The CG regimen consisted of carboplatin (AUC 4 to 5) on day 1 plus gemcitabine (1,000 mg/m(2)) on day 1 and 8, every three weeks, while the CP regimen was carboplatin (AUC 6) on day 1 plus paclitaxel (70 mg/m(2)) on day 1, 8 and 15, every four weeks. There was a total of 62 patients, 23 on the CG regimen and 39 on the CP regimen. In initial treatment, the response rate, time to progression and median survival time in the CG regimen and CP regimens were 40% vs 22%, 124 days vs 67 days, and 422 days vs 328 days, respectively. There was no statistical difference in the outcome. However, the toxicity profile was different in the two regimens. Grade 3/4 neutropenia and thrombocytopenia were frequent in the CG regimen (61% vs 31%, p=0.02, 44% vs 3%, p=0.0002, respectively). Non hematological toxicity including grade 2 alopecia was less in the CG regimen (4% vs 36%, p=0.012). In choosing the chemotherapeutic regimen for non small cell cancer, it is important to consider the toxicity.     

A phase II evaluation of weekly paclitaxel plus carboplatin in advanced urothelial cancer

This Phase II trial was designed to evaluate the overall objective response rate, complete response rate, efficacy, and safety of weekly paclitaxel (Taxol) and carboplatin (Paraplatin) in the treatment of advanced urothelial carcinoma. Thirty-three patients with measurable, unresectable, stage III-IV carcinoma of the urothelium were enrolled. Paclitaxel (135 mg/m2) and carboplatin (AUC=2) were given by intravenous (IV) infusion weekly x 6 followed by two weeks rest. Patients were premedicated with oral dexamethasone, diphenhydramine, and cimetadine (or equivalent). Patient characteristics included an Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0 (36%), one (36%), two (28%); median age 70 years (37-83); 29 (88%) male, four (12%) female; 16 (48%) patients had prior chemotherapy [eight postoperative (adjuvant), five neoadjuvant, three for metastatic disease] and eight (24%) had prior radiation therapy. Eight patients (24%) achieved objective responses, three complete responses (CR) and five partial responses (PR); one patient was not evaluable (patient died prior to first dose). The median duration of response was 13 months (range, 2-29). Nine patients (27%) had stable disease (SD) and 15 patients (45%) had progressive disease (PD). Median time to progression was 3.6 months (range, < 1-29) and median survival was 10.3 months (range, < 1-33). Grade 3 and 4 toxicities included: asthenia (46%), neutropenia (36%), leukopenia (15%), thromboembolism (12%), diarrhea (9%), nausea and vomiting (9%), hyperglycemia (7%), and neuropathy (6%). Two patients died of sepsis, one death was treatment-related. Weekly paclitaxel plus carboplatin shows promising activity; however in the current study, efficacy may have been limited by the toxicities associated with this dose-intensive regimen in an elderly, pretreated patient population with poor performance status. This regimen warrants further study, perhaps as a three out of four week regimen or at reduced doses.