Combination chemotherapy of paclitaxel, carboplatin and gemcitabine in patients who have received prior cisplatin-based chemotherapy

The objective of this study was to evaluate the efficacy and toxicity of combination chemotherapy with paclitaxel, carboplatin and gemcitabine in patients with advanced urothelial carcinoma, who have received prior cisplatin-based chemotherapy. Eligible patients had pathologically proven measurable metastatic urothelial carcinoma. Between April 2005 and May 2009, 8 patients with a mean age of 7 0 years were treated every 3 weeks with paclitaxel (200 mg/m2 on day 1), carboplatin (AUC= 5/body on day 1) and gemcitabine (800 mg/m2 on day 1 and 8). A total of 4 0 (median 4) cycles were administered. None of the 8 patients achieved a complete response(CR), but 3 patients (37. 5%) achieved a partial response (PR) and 3 were stable with the disease(SD). The median overall survival time and the median progression-free survival time were 8. 0 and 4. 5 months, respectively. Grade 4 hematological toxicities included neutropenia in 6 cycles (15. 0%), thrombocytopenia in 8 cycles (20. 0%) and anemia in 11 cycles (27. 5%). Three of the 8 patients had febrile neutropenic episodes, and no toxic death was observed. Our results suggest that the combination chemotherapy of paclitaxel, carboplatin and gemcitabine was effective, and an acceptable treatment for patients with advanced urothelial carcinoma who have received prior cisplatin-based chemotherapy.     

Paclitaxel, carboplatin, and gemcitabine in the treatment of patients with advanced transitional cell carcinoma of the urothelium

BACKGROUND: The objective of the current study was to evaluate the efficacy and toxicity of combination chemotherapy with paclitaxel, carboplatin, and gemcitabine in patients with advanced urothelial carcinoma. METHODS: Patients with metastatic or locally unresectable transitional cell carcinoma of the urothelium who had received either no or one previous systemic chemotherapy regimen were eligible. All patients received chemotherapy with intravenous paclitaxel at a dose of 200 mg/m(2) on Day 1, intravenous carboplatin at an area under the serum concentration-time curve of 5.0 on Day 1, and intravenous gemcitabine at a dose of 1000 mg/m(2) on Days 1 and 8. Treatment courses were repeated every 21 days. Patients were evaluated for response after they completed two treatment courses; patients who achieved an objective response and stable disease continued treatment for a total of six courses or until tumor progression. RESULTS: Sixty patients were treated between January 2000 and September 2003. Thirty-five patients (58%) had > or = 1 visceral sites of metastases, and only 4 patients (7%) had received any previous systemic chemotherapy. Twenty-six patients (43%) had achieved objective responses to treatment (12% complete responses). The median actuarial survival was 11 months, and the actuarial 1-year and 2-year survival rates were 46% and 27%, respectively. Myelosuppression was the most frequent toxicity, and Grade 3-4 neutropenia (using the National Cancer Institute Common Toxicity Criteria [version 2.0]) occurred in 72% of patients (46% of courses). Ten patients were hospitalized for the treatment of neutropenia and fever, and 1 patient died of treatment-related causes. Nonhematologic toxicities were relatively uncommon. CONCLUSIONS: The combination of paclitaxel, carboplatin, and gemcitabine was an active and tolerable regimen for patients with advanced urothelial carcinoma. However, the regimen was more toxic and showed no obvious incremental increase in efficacy compared retrospectively with various two-drug regimens.     

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

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 m(2) and <60 mL/min/1.73 m(2); and/or 3) prior nephrectomy. Patients received treatment with doxorubicin plus gemcitabine every other week x 5 cycles followed by paclitaxel plus carboplatin weekly x 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 > or = 3 nonhematologic toxicities were infrequent with the exception of grade > or = 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.     

Gemcitabine and paclitaxel chemotherapy for advanced urothelial carcinoma in patients who have received prior cisplatin-based chemotherapy

Background  The objective of this study was to evaluate the efficacy and toxicity of combination chemotherapy with gemcitabine and paclitaxel as a second-line regimen in patients with advanced urothelial carcinoma. Methods  Twenty patients with advanced urothelial carcinoma who were resistant to an M-VAC (methotrexate, vinblastine, doxorubicin, and cisplatin) chemotherapy regimen were administered chemotherapy consisting of intravenous gemcitabine 2500 mg/m² and paclitaxel 150 mg/m² (GP) every 2 or 3 weeks. Results  The patients received a median of 7.7 cycles of treatment (range, 2–20 cycles). Six of the 20 patients (30%; 95% confidence interval [CI], 10%–50%) had a major response to treatment (a complete response [CR] in 5% and a partial response [PR] in 25%). Seven patients (35%) had stable disease (SD). The median duration of response was 4.5 months (range, 1–9 months) and the disease control rate (CR + PR + SD) was 65%. The median survival was 11.5 months (range, 2–22 months) and the 1-year survival rate was 35%. The patients tolerated this regimen well, with only grade 3–4 neutropenia being observed in 6 patients (30%), anemia in 3 (15%), and thrombocytopenia in 1 (5%). The response rate to M-VAC in the first-line chemotherapy was significantly associated with the response to GP as the second-line chemotherapy. Conclusion  The combination of gemcitabine and paclitaxel is active and well tolerated as a second-line treatment in patients with advanced urothelial carcinoma.     

Phase II study of paclitaxel plus carboplatin in patients with advanced carcinoma of the urothelium and renal dysfunction (E2896): a trial of the Eastern Cooperative Oncology Group

BACKGROUND: Chemotherapy options for the patients with advanced urothelial carcinoma and renal dysfunction are limited. The authors performed a Phase II trial of paclitaxel plus carboplatin in patients with advanced carcinoma of the urothelium and renal dysfunction. METHODS: Forty-two patients were accrued; 37 eligible patients were treated. Patients received paclitaxel 225 mg/m(2) over three hours followed by carboplatin targeted area under the concentration-time curve = 6 mg/mL. minute every three weeks for up to six cycles. RESULTS: The median number of cycles received was four (range, one to six). The objective response rate was 24.3% (95% confidence interval, 11.9-41.7%). The median progression free survival was 3 months and the median overall survival was 7.1 months. The number of poor prognostic risk factors (Eastern Cooperative Oncology Group performance status > 1 or lung, liver, or bone metastases) significantly predicted for survival. The most common > or = 1 Grade 3 toxicities included granulocytopenia (60%) and neurotoxicity (35%). CONCLUSIONS: Paclitaxel/carboplatin is a chemotherapy option for patients with advanced urothelial carcinoma and renal dysfunction. Future trials in chemotherapy development for this patient population are warranted.     

Phase I combination trial of gemcitabine,paclitaxel, and carboplatin in patients with advanced malignancy

PURPOSE. We performed a phase I trial of carboplatin and paclitaxel in combination with gemcitabine in order to determine the tolerability of this triplet. METHODS. Enrolled in the study were 26 patients with advanced cancer, most with non-small cell lung cancer. The patients received escalating doses of carboplatin and paclitaxel on day 1 and gemcitabine (30-min infusion) on days 1, 8, and 15 of a 28-day treatment cycle. The doses of each drug ranged from an area under the concentration-time curve (AUC) of 5 to 6 for carboplatin, 135 to 175 mg/m(2) for paclitaxel, and 300 to 1000 mg/m(2) for gemcitabine. RESULTS. Hematologic toxicity was the most commonly observed toxicity and was dose-limiting. During the first cycle at the recommended phase II dose, there were two instances of grade 4 neutropenia and one instance of grade 4 thrombocytopenia among six patients, none of which was dose-limiting. Cumulative hematologic toxicity emerged in subsequent cycles. Non-hematologic toxicities were mild. Five patients, all with previously untreated non-small-cell lung cancer (NSCLC), had a partial response. Nine patients with NSCLC or upper gastrointestinal malignancies experienced stable disease. CONCLUSIONS. Based on significant neutropenia and thrombocytopenia, the regimen recommended for further study consists of carboplatin AUC 5, paclitaxel 175 mg/m(2), and gemcitabine 1000 mg/m(2) on a 28-day cycle. The antitumor activity noted suggests that further investigation of this well-tolerated combination in specific tumor types, especially NSCLC, is warranted.     

Phase 2 trial of pemetrexed disodium and gemcitabine in advanced urothelial cancer (E4802): a trial of the Eastern Cooperative Oncology Group

BACKGROUND: There is a need to identify active new regimens in patients with advanced urothelial cancer. Pemetrexed and gemcitabine are active agents in advanced urothelial cancer. A phase 2 trial of the combination of these 2 agents was performed in patients with advanced urothelial cancer who were previously untreated for metastatic disease. METHODS: Forty-six patients with advanced urothelial carcinoma received pemetrexed disodium 500 mg/m2 and gemcitabine 1000 mg/m2 intravenously on Day 1, with gemcitabine repeated on Day 8. Cycles were repeated every 3 weeks for a maximum of 6 cycles. RESULTS: Two patients attained a complete response, and 12 patients attained a partial response for an overall response rate of 31.8% (90% confidence interval, 20.4%-45.2%). The median time to disease progression was 5.8 months, and the median overall survival was 13.4 months. Thirty-three patients (75%) experienced grade>or=3 neutropenia, and 5 patients (11%) had febrile neutropenia. There were 2 therapy-related deaths. CONCLUSIONS: The combination of pemetrexed and gemcitabine had moderate antitumor activity in previously untreated patients with advanced urothelial cancer at the expense of significant myelosuppression.     

A phase II study of weekly paclitaxel combined with carboplatin for elderly patients with advanced non-small cell lung cancer

We conducted this phase II study to explore the efficacy and safety of weekly paclitaxel combined with carboplatin in elderly patients with advanced non-small cell lung cancer (NSCLC). Elderly patients (> or = 70 years old) of stage IIIB, IV, or recurrent NSCLC with PS 0 or 1 were enrolled. Patients received paclitaxel at a dose of 70 mg/m2 on Days 1, 8, 15, and carboplatin at the target dose of the area under the curve (AUC) of six on Day 1 every 28 days for at least two cycles. Forty-two patients were enrolled and 40 patients were treated with a median of three cycles (range, 1-5). The overall response rate (ORR) was 45% (95% confidence interval, 30-60%). The median survival time (MST) was 14 months and the 1-year survival rate was 62%. Twenty-eight patients (70%) had grade 3/4 neutropenia and two patients (5%) experienced grade 3 febrile neutropenia. Non-hematological toxicities were generally mild to moderate and grade 3 peripheral neuropathy was seen in one patient (3%). There was one treatment-related death by infection due to neutropenia. Weekly paclitaxel and carboplatin combination chemotherapy was an effective and safe regimen in elderly patients with advanced NSCLC. A randomized trial comparing this treatment with the conventional tri-weekly regimen of paclitaxel and carboplatin is warranted.     

Phase I study of carboplatin, doxorubicin and weekly paclitaxel in patients with advanced ovarian carcinoma.

BACKGROUND: Doxorubicin is an active compound in epithelial ovarian cancer (EOC), but adding it to carboplatin-paclitaxel causes toxicity. Toxicity can be reduced by weekly administration. We examined the tolerability of weekly paclitaxel in combination with carboplatin and doxorubicin. PATIENTS AND METHODS: Chemotherapy na?ve patients with EOC were treated with doxorubicin (50 mg/m(2) day 1), carboplatin (AUC 6 day 1) and paclitaxel (days 1, 8, 15, 21), 28-day cycle. Three patients were treated at each paclitaxel dose level, starting at 60, 75 and 90 mg/m(2)/week. If more than two patients in a cohort experienced dose-limiting toxicity (DLT) three more patients were treated at the dose level below. RESULTS: Twelve patients with advanced EOC received a median of six cycles (range 2-6) of the three-drug combination. DLT occurred at dose level 3: prolonged grade 4 febrile neutropenia, 1 patient; grade 3 peripheral neuropathy, 1 patient. All six patients treated at dose level 2 experienced short-lived grade 4 neutropenia, which led to dose modifications resulting in an actual delivered dose of paclitaxel of 64 mg/m(2)/week. Eight out of 12 patients had measurable disease on CT scan: four obtained a partial remission; three had stable disease. CONCLUSIONS: The combination of carboplatin, doxorubicin and paclitaxel in patients with EOC is active and its main toxicity is myelosuppression. Dose intensity of paclitaxel can be maintained in a three-drug combination through weekly administration (65 mg/m(2)).     

Chemotherapy with gemcitabine, paclitaxel, and cisplatin in the treatment of patients with advanced transitional cell carcinoma of the urothelium

Chemotherapeutic agents are active in advanced bladder cancer, and various combinations have shown promising results. The objective of this study was to evaluate the efficacy of combination chemotherapy with gemcitabine, paclitaxel, and cisplatin in patients with advanced urothelial carcinoma. Fifty-nine patients with metastatic or locally advanced transitional cell carcinoma of the urothelium were treated between 2000 and 2005. No patient had received any previous systemic chemotherapy. All patients received chemotherapy intravenously with gemcitabine at a dose of 1000 mg/m(2) on days 1 and 8, paclitaxel at a dose of 80 mg/m(2) on days 1 and 8, and cisplatin at a dose of 50 mg/m(2) on day 2. Treatment courses were repeated every 21 days. After completion of four to six courses in this regimen an intravenous application of gemcitabine was repeated every 28 days at a dose of 1000 mg/m(2). Fifty-nine patients were treated between 2000 and 2005. Nine patients (15%) had >or=1 visceral site of metastases, and no patient had received any previous systemic chemotherapy. Forty-eight patients (81%) achieved objective responses to treatment (56% complete responses). The median actuarial survival was 22 months, and the actuarial 1-year and 2-year survival rates were 68% and 39%, respectively. After a median follow-up of 17.5 months, 29 patients remained alive and 25 were free of disease progression. The median progression-free survival for the entire group was 10 months. The median survival time for patients with an Eastern Cooperative Oncology Group (ECOG) status of 0, 1, and 2 was 37.5, 17, and 12 months, respectively. Grade 3-4 neutropenia occurred in 39% of the patients. The combination of gemcitabine, paclitaxel, and cisplatin is a highly effective and tolerable regimen for patients with advanced urothelial carcinoma. This treatment should be considered as a suitable option that deserves further prospective evaluation. The ECOG performance status is an important predictive factor for survival.     

Paclitaxel and gemcitabine chemotherapy for advanced transitional-cell carcinoma of the urothelial tract: a phase II trial of the Minnie pearl cancer research network.

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/m(2) by 1-hour intravenous (IV) infusion on day 1 and gemcitabine 1,000 mg/m(2) 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.     

Gemcitabine and docetaxel as first-line treatment for advanced urothelial carcinoma: a phase II study

The purpose of the study was to investigate the toxicity and efficacy of the combination of gemcitabine and docetaxel in untreated advanced urothelial carcinoma. Patients with previously untreated, locally advanced/recurrent or metastatic urothelial carcinoma stage-IV disease were eligible. Patients with Performance status: PS ECOG >3 or age >75 years or creatinine clearance <50 ml min(-1) were excluded. Study treatment consisted of docetaxel 75 mg m(-2) (day 8) and gemcitabine 1000 mg m(-2) (days 1+8), every 21 days for a total of six to nine cycles. A total of 31 patients with urothelial bladder cancer, 25 men and six women, aged 42-74 (median 64) years were enrolled. The majority of patients had a good PS (51.6%; PS 0). In all, 15 (48.3%) patients had locally advanced or recurrent disease only and 16 (54.8%) presented with distant metastatic spread, with multiple site involvement in 22.5%. Toxicity was primarily haematologic, and the most frequent grade 3-4 toxicities were anaemia 11 (6.7%) thrombocytopenia eight (4.9%), and neutropenia 45 (27.6%), with 10 (6.1%) episodes of febrile neutropenia. No toxic deaths occurred. A number of patients had some cardiovascular morbidity (38.7%). Nonhaematological toxicities except alopecia (29 patients) were mild. Overall response rate was 51.6%, including four complete responses (12.9%) and 12 partial responses (38.7%), while a further five patients had disease stabilisation (s.d. 16.1%). The median time to progression was 8 months (95% CI 5.1-9.2 months) and the median overall survival was 15 months (95% CI 11.2-18.5 months), with 1-year survival rate of 60%. In conclusion, this schedule of gemcitabine and docetaxel is very active and well tolerated as a first-line treatment for advanced/relapsing or metastatic urothelial carcinoma. Although its relative efficacy and tolerance as compared to classic MVAC should be assessed in a phase III setting, the favourable toxicity profile of this regimen may offer an interesting alternative, particularly in patients with compromised renal function or cardiovascular disease.     

The combination of gemcitabine and carboplatin as first-line treatment in patients with advanced urothelial carcinoma. A Phase II study of the Hellenic Cooperative Oncology Group

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.     

Gemcitabine and oxaliplatin: a safe and active regimen in poor prognosis advanced non-small cell lung cancer patients

BACKGROUND AND AIMS: Most patients with non-small cell lung cancer (NSCLC) cannot tolerate a cisplatin-based chemotherapy because of old age, general conditions, and/or multiorgan metastatic sites. Oxaliplatin is active in NSCLC, offers advantage in terms of toxicity, and shows synergism with gemcitabine. The aims of this phase II study were to evaluate the response rate and toxicity of the gemcitabine-oxaliplatin combination in patients with advanced NSCLC and poor prognosis. METHODS: Patients were given a gemcitabine infusion (1000 mg/m(2) over 30 min on days 1 and 8) followed by oxaliplatin (65 mg/m(2) over 120 min on days 1 and 8) every 21 days for six cycles. RESULTS: Thirty-two patients with poor-prognosis advanced NSCLC received 136 cycles. There were 25 males and seven females, and the median age was 65 years (range 29-76). Fifty-six percent of patients had adenocarcinoma, and 31% had squamous cell carcinoma. Sixty-six percent of patients had stage IV disease, and 34% had stage IIIB disease. Eastern cooperative oncology group (ECOG) performance status was 2-3 in 50%, 1 in 44%, and 0 in 6% of patients. Eight patients (25%) had been previously treated with cisplatin or carboplatin. All patients were symptomatic. Of the 32 patients who received study drug, five (16%) achieved partial response, six (19%) had minor response, three (9%) had stable disease, and 15 (47%) progressed. The median overall survival was 27 weeks. Thirty-one patients were evaluable for toxicity: seven patients (23%) had grade 3-4 thrombocytopenia with no bleeding; four patients (13%) had grade 3-4 neutropenia with no febrile neutropenia, and three patients (10%) had grade 3 anemia. Two patients (6%) had grade 3, and six patients (19%) had grade 1-2 neurotoxicity. CONCLUSION: The combination of gemcitabine and oxaliplatin seems to be well tolerated and active in patients with poor prognosis advanced NSCLC and deserves further evaluation in phase II clinical trials.     

Phase II trial of a paclitaxel and carboplatin combination in Asian patients with metastatic nasopharyngeal carcinoma

Purpose: An earlier phase II trial of paclitaxel in patients with metastatic nasopharyngeal carcinoma (NPC) demonstrated a response rate of 22%. Hence we proceeded to study the combination of paclitaxel and carboplatin in these patients.Patients and methods: The 21-day regimen was as follows: i.v. paclitaxel 175 mg/m2 over three hours preceded by standard premedications, followed by i.v. carboplatin dosed at AUC of six infused over one hour. Only chemotherapy-naïve patients with histological diagnoses of undifferentiated carcinoma of the nasopharynx, systemic metastases and radiologically measurable lesions were eligible.Results: Thirty-two patients were accrued to this study. Twenty patients (62%) had at least two sites of metastasis. The main grade 3–4 toxicity was neutropenia (31%). Nine patients (28%) developed neutropenic sepsis, which caused the demise of one of them. Twenty-four patients (75%) responded to treatment, with one (3%) attaining a complete response. The median time to progression of disease was seven months and the median survival was 12 months. At one year, 52% of the patients were alive.Conclusions: The combination of paclitaxel and carboplatin is an active regimen in NPC. Its convenience of administration and good tolerability make it an attractive alternative regimen to consider for patients with metastatic disease.     

Phase II trial of carboplatin and paclitaxel in cisplatin-pretreated advanced transitional cell carcinoma: a Southwest Oncology Group study

BACKGROUND: The purpose of the study was to assess the efficacy and toxicity of carboplatin and paclitaxel administered every 3 weeks in patients with advanced urothelial carcinoma, previously treated with cisplatin-based therapy. METHODS: Eligibility included metastatic or locally advanced unresectable transitional cell carcinoma of the urothelial tract. Prior chemotherapy, except taxanes, was permitted within 12 months. Adequate hematologic, hepatic, and renal function and a performance status of 0-2 were required. Treatment consisted of paclitaxel 200 mg/m2 intravenously for 3 hours followed by carboplatin, target area under the curve = 5 repeated every 3 weeks. RESULTS: Forty-four patients were enrolled. Thirty-four (77%) patients had a performance status of 0 or 1. Twenty-five (57%) of the patients had received prior neoadjuvant or adjuvant chemotherapy, and 19 (43%) had received it for metastatic disease. In all, 181 cycles were administered (median, 3.5 cycles; range, 1-11 cycles). The predominant NCI CTC (version 2.0) Grades 3 and 4 toxicities consisted of myelosuppression in 28 patients and neuropathy in 11 patients. There were no treatment-related deaths. Of the 44 patients, 1 (2%) had a complete response, 2 (5%) had a partial response, and 4 (9%) had an unconfirmed partial response, for an overall response rate of 16% (95% confidence interval [CI] 7-30%). The median progression-free survival was 4 months (95% CI 3-5 months) and the median survival was 6 months (95% CI 5-8 months). CONCLUSIONS: Carboplatin and paclitaxel combination is well tolerated and has modest activity in platinum refractory advanced urothelial carcinoma. Effective regimens need to be developed in cisplatin-pretreated urothelial carcinoma.     

Phase II study of 24-hour infusion of paclitaxel (Intaxel) with carboplatin in advanced non-small cell lung cancer

PURPOSE: To determine the activity and toxicity of combined 24-hour infusion of paclitaxel with carboplatin in advanced non-small cell lung cancer. PATIENTS AND METHODS: Eligibility required measurable disease; stage III B with malignant pleural effusion or stage IV disease, with a performance status (PS) of ECOG 0-2. Chemotherapy consisted of 24 hours continuous infusion of paclitaxel at 135 mg/m(2) on day 1, followed by carboplatin (AUC=6) on day 2. Treatment was repeated at 3-week intervals for a total of 6 cycles. RESULTS: Thirty-nine patients were enrolled. Twenty six patients were male and 13 female, with a median age of 57 years (range, 38 to 72). Six patients (15%) had stage III B and 33 (85%) had stage IV. PS 0-1/2 was 67%/33%. A total of 131 cycles was administered and the median number of cycles was 4 (range, 2-6). Grade 3-4 neutropenia, grade 3-4 leukopenia and grade 3 anemia occurred in 3%, 3% and 23%, respectively. One patient (3%) developed febrile neutropenia. Grade 3 diarrhea occurred in 3 patients (8%). Other non-hematologic toxicities were mild including mucositis and skin rash. The overall response rate was 15%. Median survival was 8 months (range 6-9.5 months) and 1-year survival rate was 20%. CONCLUSIONS: The combined 24-hour infusion of paclitaxel (Intaxel) with carboplatin is a feasible and well-tolerated regimen in the treatment of advanced NSCLC patients.     

Carboplatin and gemcitabine in metastatic transitional cell carcinoma of the urothelium: Effective treatment of patients with poor prognostic features

Purpose:To evaluate the activity and toxicity of gemcitabine andcarboplatin in consecutive patients presenting with locally advanced ormetastatic transitional cell carcinoma of the urothelium (TCC). Patients and methods:Seventeen consecutive patients referred toa single institution with locally advanced or metastatic TCC were treated withcarboplatin AUC 5 on day 1 and gemcitabine 1000 mg/m² on day 1 and8 of a 21-day cycle. All patients were assessable for response and toxicity.Minimal eligibility criteria were used to minimize patient selection. Results:Seventeen patients with measurable stage IV TCC of theurothelium were treated. The median age was 69 years (range 54–78), themedian creatinine clearance was 56 ml/min (range 34–90) and 30%of patients had an ECOG performance score of two. Nine patients (53%)had visceral metastases and the majority of patients had multiple sites ofmetastases. There were three complete responses, seven partial responses, foran overall response rate of 58.8%. Responses were seen at all sitesincluding the liver. One patient had a response within a previously irradiatedfield and three patients with prior chemotherapy had responses. Median overallsurvival was 10.5 months and median time to progression was 4.6 months.Toxicity was primarily haematologic with six patients having grade 3neutropenia and six patients with grade 4 neutropenia. There were five casesof grade 3 and three cases of grade 4 thrombocytopenia. There were no episodesof febrile neutropenia and only one patient required admission for managementof toxicity. Thirteen patients required dose reduction or delay due toneutropenia or thrombocytopenia. There were no treatment-related deaths. Conclusion:The combination of carboplatin and gemcitabine isactive in metastatic transitional cell carcinoma of the urothelium withmanageable toxicity in a relatively elderly group of patients with some poorprognostic features.     

Phase II trial of gemcitabine/carboplatin followed by paclitaxel in patients with performance status=2,3 or other significant co-morbidity (HIV infection or s/p organ transplantation) in advanced non-small cell lung cancer

INTRODUCTION: The role of chemotherapy in patients with advanced non-small cell lung cancer and poor performance status or who have HIV disease or organ transplantation is unclear. While survival appears to be enhanced, serious toxicity may occur. We evaluated the efficacy of sequential, dose attenuated carboplatin/gemcitabine followed by paclitaxel in patients with PS=2,3, HIV infection or after solid organ transplantation. PATIENTS AND METHODS: Chemotherapy naive patients with PS 2,3 or who were HIV positive or post solid organ transplantation were eligible. Treatment consisted of gemcitabine: 1000 mg/m(2) d 1,8 carboplatin: AUC=5 d 1 q 21d x 2 followed by paclitaxel 80 mg/m(2) q wk x 6 followed by a 2 week break and then repeated until progression. RESULTS: 47 patients were entered. Stage IIIb/IV: 8/39, PS 2/3=26/19, HIV infection=2, solid organ transplantation=2. 12 (25%) had brain metastases. Thirty-nine patients completed two cycles of carboplatin/gemcitabine and 29 pts received at least one cycle of paclitaxel. Overall response rate was 19% (95% CI 1.2-31.7%). Median event free, overall and 1-year survivals were 3.3 months, 5.8 months and 8.4%. Toxicity was moderate with 19% experiencing grade 4 neutropenia (11% with febrile neutropenia). CONCLUSIONS: Sequential carboplatin/gemcitabine to paclitaxel is well tolerated and active in this population. The survival seen is comparable to that of other regimens utilized in PS=2 patients with superior tolerability however, the prognosis for these patients is very poor even with treatment. This is the first trial to prospectively evaluate chemotherapy for patients with HIV disease or organ transplantation and 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.