Clinical study of combination chemotherapy of methotrexate, epirubicin and nedaplatin (MEN) in patients with advanced urothelial carcinoma

The toxicity of platinum-based chemotherapies is a common problem for patients with advanced urothelial carcinoma. We performed a prospective study to assess the efficacy and safety of the combination chemotherapy of methotrexate, epirubicin and nedaplatin (MEN) as first-line treatment in patients with advanced urothelial carcinoma. Eligible patients had pathologically proven measurable unresectable or metastatic urothelial carcinoma. Between February 2003 and February 2006, 11 patients with a mean age of 70 years were treated every 3 weeks with methotrexate (30 mg/m(2) on day 1) and epirubicin (50 mg/m(2) on day 1) and nedaplatin (80 mg/m(2) on day 2). A median of 2.6 cycles were administered. None of the 11 patients achieved a complete response (CR), but 6 patients (55%) achieved a partial response (PR) with a median duration of response of 10 months, and no responses occurred in 4 patients. The median survival time was 11 months. Grade 4 hematological toxicities included neutropenia in 1 case (9%), thrombocytopenia in 2 cases (19%) and anemia in 1 case (9%). None of the 11 patients had febrile neutropenic episodes, and no toxic death was observed. Our results suggest that the combination chemotherapy of methotrexate, epirubicin and nedaplatin (MEN) was effective and acceptable treatment in patients with advanced urothelial carcinoma.     

吉西他滨联合奥沙利铂双周方案治疗尿路上皮癌的可行性分析

目的：初步评价吉西他滨联合奥沙利铂（GEMOX）双周方案治疗尿路上皮癌的疗效和安全性。方法选取20例浸润性或转移性尿路上皮癌患者,患者均为男性,中位年龄62岁,其中6例超过70岁,7例接受过单侧肾切除术;辅助化疗6例,一线化疗14例。给予吉西他滨1000 mg/m2静脉滴注d1,奥沙利铂85 mg/m2静脉滴注d2;每2周为一个周期。评价患者近期疗效及不良反应,同时观察无进展生存期（PFS）或者无病生存期（DFS）以及总生存期（OS）。结果全部患者共接受GEMOX方案化疗106周期,中位化疗5周期。14例一线化疗患者中位随访24个月,12例死亡,中位PFS为5个月,中位OS为14个月;10例患者可评价客观疗效,PR 4例（40%）,SD 4例（40%）,PD 2例（20%）。6例辅助化疗患者中位随访51个月,1例复发死亡,5例无病生存,尚未到达中位DFS和OS。消化道反应和骨髓抑制是最常见的不良反应,中性粒细胞下降（15.8%）是最常见3~4级不良反应。结论GEMOX方案治疗尿路上皮癌耐受良好,在一线化疗中展现了较好的疗效,值得在老年患者或具有肾功能不全高危风险的患者中进一步研究。     

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.     

Treatment results including more than third-line chemotherapy for patients with advanced non-small cell lung cancer

Recently, third-line chemotherapy for advanced non-small cell lung cancer (NSCLC) was accepted as a reasonable therapeutic option in patients with a favorable performance status. In practice, however, palliative chemotherapy has been performed for patients with a favorable performance status, even after third-line chemotherapy. Although multiple cycles of palliative chemotherapy were performed for these patients, there are little data of observation for courses of treatment from first-line to the last chemotherapy. We reviewed the courses of treatment for 82 patients with advanced NSCLC that had been admitted for platinum-based chemotherapy as a first-line treatment. Additional cycles of palliative chemotherapy were provided as monotherapy, based on the attending physician's decision considering patient performance status and toxicity after disease progression for previous chemotherapy. The median number of chemotherapy lines and cycles were 2 and 7, respectively, from first-line to the last chemotherapy. The median overall survival was 24 months in the response group of first-line chemotherapy, compared to 15 months for the entire study group. In the response group, the median number of chemotherapy cycles was 15 and patients received a median of 3 lines of chemotherapy. A total of 33 patients were candidate third-line chemotherapy or more. The median survival was 23 months for patients treated with more than third-line chemotherapy, compared to 7 months for patients treated with less than second-line chemotherapy. We conclude that long-standing chemotherapy is not beneficial to all NSCLC patients. However, patients with a favorable response to first-line chemotherapy tend to receive a higher number and more cycles of chemotherapy than the non-response group. Furthermore, multi-line chemotherapy appears to increase survival in the response group. Further studies will be needed to confirm these results.     

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.     

The role of palliative chemotherapy for advanced pulmonary pleomorphic carcinoma

Pulmonary pleomorphic carcinoma is an uncommon malignant tumor of the lung, which has the dual cell components of spindle or giant cells and epithelial cells. The objective of this study was to investigate the clinical course and efficacy of palliative chemotherapy in patients with advanced pulmonary pleomorphic carcinoma. Twelve patients were diagnosed with advanced pulmonary pleomorphic carcinoma and received palliative chemotherapy from February 2000 to December 2007. Among the 12 patients, five patients received gemcitabine/cisplatin, three patients received gemcitabine/carboplatin, two patients received paclitaxel/carboplatin, one patient received paclitaxel/cisplatin, and one patient received docetaxel/cisplatin as first-line chemotherapy. The median patient's age was 62 (range, 32–72 years). Among the 12 patients, nine patients had relapsed disease after curative resection and three patients had metastatic disease at the initial presentation. After treatment with first-line palliative chemotherapy, seven patients (58%) had progressive disease, three patients (25%) had stable disease, and only two patients (17%) had a partial response. The median overall survival from the day of initiation of first-line chemotherapy was only 8 months (95% CI, 6–10) with median follow-up of 26 months. These results showed the dismal prognosis and the poor response to chemotherapy of advanced pulmonary pleomorphic carcinoma. Further studies are needed to investigate whether the current strategy of palliative chemotherapy for the treatment of advanced pulmonary pleomorphic carcinoma can be justified or not. Moreover, additional novel treatment approaches are required.     

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.     

Combination phase I study of nedaplatin and gemcitabine for advanced non-small-cell lung cancer

To establish the toxicities and maximum tolerated dose (MTD) of nedaplatin with gemcitabine, and to observe their antitumour activity, we conducted a combination phase I study in advanced non-small-cell lung cancer (NSCLC). Patients received nedaplatin (60-100 mg m(-2) given intravenously over 90 min) on day 1, and gemcitabine (800-1000 mg m(-2) given intravenously over 30 min) on days 1, 8, every 3 weeks. In total, 20 patients with locally advanced or metastatic NSCLC who received no prior chemotherapy or one previous chemotherapy regimen were enrolled. The most frequent toxicities were neutropenia and thrombocytopenia; nonhaematological toxicities were generally mild. Three out of six patients experienced dose-limiting toxicities (neutropenia, thrombocytopenia and delayed anaemia) at dose level 4, 100 mg m(-2) nedaplatin with 1000 mg m(-2) gemcitabine, which was regarded as the MTD. There were three partial responses, for an overall response rate of 16.7%. The median survival time and 1-year survival rate were 9.1 months and 34.1%, respectively. This combination is well tolerated and active for advanced NSCLC. The recommended dose is 80 mg m(-2) nedaplatin with 1000 mg m(-2) gemcitabine. This combination chemotherapy warrants a phase II study and further evaluation in prospective randomised trials with cisplatin- or carboplatin-based combinations as first-line chemotherapy for advanced NSCLC.     

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.     

Sequential gemcitabine and cisplatin followed by docetaxel as first-line treatment of advanced urothelial carcinoma: a multicenter phase II study of the Hellenic Oncology Research Group.

BACKGROUND: The purpose of this study was to investigate the toxicity and efficacy of the sequential administration of gemcitabine (GMB) in combination with cisplatin (CDDP) followed by docetaxel (Taxotere) as first-line treatment of advanced urothelial carcinoma. PATIENTS AND METHODS: Patients [aged 相似文献   

Efficacy of third-line pemetrexed monotherapy versus pemetrexed combination with bevacizumab in patients with advanced EGFR mutation-positive lung adenocarcinoma

Objective

The purposes of this study were to observe the effects of different treatment strategies, including third-line pemetrexed alone versus its combination with bevacizumab, in patients with advanced epidermal growth factor receptor (EGFR) mutation-positive lung adenocarcinoma, and to analyze the effects of the different medication orders of first- and second-line drugs on third-line efficacy.

Patients and methods

One hundred and sixteen cases of patients with EGFR-positive lung adenocarcinoma who had received third-line pemetrexed alone or in combination with bevacizumab between March 2010 and March 2014 at Guangzhou Institute of Respiratory Diseases, the First Affiliated Hospital of Guangzhou Medical University were analyzed retrospectively. Additionally, all the patients were treated with first-line gemcitabine and cisplatin (GP) chemotherapy and second-line EGFR tyrosine kinase inhibitor (TKI) or with first-line EGFR-TKI and second-line GP chemotherapy.

Results

The median survival of 61 cases with third-line pemetrexed monotherapy was 36.22 months, the median survival time of 55 cases with third-line pemetrexed plus bevacizumab was 38.76 months, and there was a significant difference in survival time between the two groups (P=0.04). Subgroup analysis revealed that among the 55 cases with third-line bevacizumab plus pemetrexed treatment, the median survival of 29 patients with first-line GP and second-line EGFR-TKI was 42.80 months, while the median survival of 26 patients with first-line EGFR-TKI and second-line GP was only 34.46 months; additionally, there was a significant difference in the survival time between the two subgroups (P=0.001). Among 61 cases with third-line pemetrexed treatment, the median survival of 34 patients with first-line GP and second-line EGFR-TKI was 38.72 months, while the median survival of 27 patients with first-line EGFR-TKI and second-line GP was only 32.94 months; the survival time of the two subgroups was significantly different (P=0.001).

Conclusions

Regardless of the order of the first- and second-line chemotherapy and TKI therapy, the pemetrexed plus bevacizumab regimen was superior to the pemetrexed monotherapy as the third-line therapy in patients with advanced EGFR-positive lung adenocarcinoma. However, this strategy is worth further investigation in prospective studies.     

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.     

Palliative chemotherapy for non-transitional cell carcinomas of the urothelial tract

Non-transitional cell carcinomas of the urothelial tract comprise 5–10% of urothelial cancers. Clinical information regarding the clinical behavior and chemotherapy outcome of non-transitional cell carcinomas of the urothelial tract are incomplete due to their rarity. The object of this study was to evaluate the clinical features and the efficacy of palliative chemotherapy in advanced non-transitional cell carcinomas of the urothelial tract. We analyzed the clinical records of 21 consecutive patients who received palliative chemotherapy for unresectable or metastatic non-transitional cell carcinomas of the urothelial tract between January 1995 and November 2007. All the 21 patients received first-line chemotherapy with platinum-based regimens which are known to be effective in transitional cell urothelial carcinomas. The median age of the patients was 57 years (range, 27–71 years). The primary sites of involvement were the bladder, urethra, urachus, and ureter in 43%, 29%, 19%, and 10% of the patients, respectively. Adenocarcinoma was the most common histological type (67%); squamous cell carcinoma and small cell carcinoma comprised 24 and 10% of the histologic types, respectively. With a median duration of follow-up of 32 months (range, 12–71 months), the median overall survival for all 21 patients from the day of first-line chemotherapy was 13 months (95% CI, 6.8–19.2). The expected 1-year survival rate was 50.6% (95% CI, 28.6–72.5). Univariate analysis showed a better median overall survival in patients with adenocarcinoma, compared to non-adenocarcinomas (47 vs. 10 months, P = 0.049). The median overall survival of patients who received platinum-based palliative chemotherapy for advanced non-transitional cell carcinomas was comparable to previous studies for patients with transitional cell carcinomas. Adenocarcinomas appear to have a favorable prognosis for the survival of the patients who received platinum-based chemotherapy for advanced non-transitional cell carcinomas.     

Capecitabine combined with gemcitabine (CapGem) as first-line treatment in patients with advanced/metastatic biliary tract carcinoma

BACKGROUND: Biliary tract carcinoma is an aggressive cancer, with median survival rarely exceeding 6 months. There is currently no established palliative standard of care. A Phase II trial was conducted to study a combination of oral capecitabine and gemcitabine (CapGem) as first-line therapy in patients with advanced and/or metastatic biliary carcinoma. METHODS: Patients with unresectable or metastatic intrahepatic or extrahepatic biliary duct carcinoma and gallbladder carcinoma were enrolled. Eligible patients had histologically or cytologically confirmed, measurable adenocarcinoma and had not received prior therapy with capecitabine or gemcitabine. Treatment consisted of intravenous (i.v.) gemcitabine (1000 mg/m(2) on Days 1 and 8) plus oral capecitabine (650 mg/m(2) twice daily on Days 1-14) every 3 weeks for up to 6 cycles. Tumor response, survival, and safety were determined. RESULTS: A total of 44 patients were evaluable. Primary tumor sites were: intrahepatic (n = 14) and extrahepatic biliary duct (n = 16); gallbladder (n = 7); and ampulla (n = 7). Fourteen (32%) patients had a partial response and 15 (34%) patients had stable disease. Median time to disease progression and overall survival were 6.0 (range, 3.8-8.1) and 14 (range, 11.4-16.6) months, respectively. The 1-year survival rate was 58%. No Grade 4 adverse events were seen. Transient Grade 3 neutropenia/thrombocytopenia and manageable (almost invariably Grade 2) nausea, diarrhea, and hand-foot syndrome were the most common adverse events. CONCLUSIONS: CapGem is an active and well tolerated first-line combination chemotherapy regimen for patients with advanced/metastatic biliary tract carcinoma that offers a convenient home-based therapy.     

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.     

Single agent paclitaxel as a first-line therapy in advanced urothelial carcinoma: its efficacy and safety in patients even with pretreatment renal insufficiency

BACKGROUND: Cisplatin-based chemotherapy is the mainstay of the treatment for advanced urothelial cancer, but patients with renal insufficiency before therapy are usually contraindicated to receiving platinum-based chemotherapy. Paclitaxel is one of the most promising agents against advanced urothelial carcinoma in recent trials and it can be easily tolerated even in patients with compromised renal function. We conducted a study in order to evaluate the efficacy and safety of paclitaxel as a first-line therapy in advanced urothelial carcinoma patients. METHODS: Thirteen advanced chemo-naive urothelial carcinoma patients with a median age of 71 years were studied, seven of them demonstrating renal insufficiency (pretreatment serum creatinine > or = 1.5 mg/dl). All 13 patients received a minimum of two cycles of paclitaxel 175 mg/m2, delivered by intravenous infusion for 3 h every 3 weeks. RESULTS: Four of the 13 patients responded to treatment, a response rate of 30.8%, with two of these achieving complete remission and two showing partial responses. The median overall survival period of all 13 patients was nine months (95% Cl: 6.51-11.49) and our study revealed a statistical tendency in the difference of median overall survival time between responders and non-responders (13 months versus 7.5 months, log-rank p = 0.038), although the number of cases was limited. The differences in response rate and median overall survival time, comparing patients with renal insufficiency and those with normal renal function, were not significant. Treatment-related toxicity was mild, with only two (15.4%) patients suffering from grade 3-4 leukopenia. No treatment-related mortality was noted. CONCLUSIONS: Single-agent paclitaxel can be used as a first-line therapy in advanced urothelial carcinoma patients, and is especially suitable for those with pretreatment renal insufficiency, since the antitumor activity is significant while toxicity is well tolerated.     

Does maintenance of Bevacizumab after treatment failure have a role in metastatic colon cancer？

Objective: To study the timing of Bevacizumab (BVC) in the overall treatment strategy of advanced metastatic colorectal cancer - early use (first-line) or later use. Methods: 41 patients with progressive metastatic colorectal carcinoma were included. Patients were randomized to receive chemotherapy with or without BVC. Primary end point was objective response. Secondary end points were median survival, time to tumor progression, and toxicity. Results: Partial response with second-line BVC group constituted 25% and 18.8% in patients with first-line chemotherapy and BVC-based regimen respectively, compared to 11.8% and 5.9% with second-line chemotherapy. Median time to progression was 3.1 vs. 2.3 months for cases with first-line chemotherapy and BVC-based regimens respectively. Median survival was 8.2 vs. 4 months in both groups respectively (P = 0.019). Conclusion: Second-line chemotherapy combined BVC had higher disease control rate (partial response and stable disease), median time to progression and median survival in BVC-naive patients compared to patients with first-line BVC-based therapy. BVC should be maintained in the second- and third-line settings, as cases with BVC discontinuation had significantly lower median time to disease progression and median survival. Selection of patients for use of BVC was recommended with taking into consideration the cost-benefit value and that the discontinuation of BVC would increase tumor progression.     

Gemcitabine and docetaxel,an effective second-line chemotherapy for lung metastasis of urothelial carcinoma

Background

The objective of this study was to evaluate the efficacy of a gemcitabine and docetaxel (GD) combination as a second-line treatment for patients with metastatic urothelial carcinoma (UC) after failure of first-line treatment with platinum-based chemotherapy.

Methods

From June 2006 to January 2012, 38 patients with metastatic UC previously treated with platinum-based chemotherapy received GD therapy. This consisted of gemcitabine 800 mg/m² and docetaxel 40 mg/m² on days 1 and 8 of each 21-day cycle as second-line chemotherapy. All the patients were evaluated for toxicity and assessed every cycle by imaging. We analyzed the efficacy of GD as second-line chemotherapy in the follow-up study.

Results

The median number of GD treatment cycles was 4 (range 2–9); the objective response rate was 47.4 %; and the median progression-free survival and median overall survival were 4.1 and 10.8 months, respectively. Univariate and multivariate analyses on the GD treated group showed that the existence of lung metastases was the only prognostic factor for tumor response. Grade 3 treatment-related toxicity included neutropenia (31.6 %) and thrombocytopenia (15.8 %), and only one patient with grade 4 toxicity had thrombocytopenia (2.6 %).

Conclusions

The GD regimen as second-line chemotherapy was especially effective for lung metastatic UC and yielded favorable results in patients whose first-line platinum-based chemotherapy had failed. Given the safety and benefit profile seen in this study, a large prospective study is warranted to consider the potential utility of GD chemotherapy as a second-line for UC.     

Weekly regimen of epirubicin and paclitaxel as second-line chemotherapy in patients with metastatic transitional cell carcinoma of urothelial tract: results of a phase II study

Until recently, there was no standard second-line treatment for advanced urothelial carcinoma. Although included in first-line regimens, role of anthracyclines was never investigated as second-line therapy. Single-agent paclitaxel showed modest results in this setting. The purpose of this study was to assess the efficacy and toxicity of concomitant weekly administration of epirubicin plus paclitaxel in patients with metastatic urothelial carcinoma previously treated with platinum-based regimens. Between March 2004 and May 2008, thirty-five consecutive pretreated patients with metastatic transitional cell carcinoma of the urothelial tract were enrolled. Median age was 64 years (range 45-72 years), and median ECOG PS was 1 (range 0-1). Patients received epirubicin 25 mg/m(2) and paclitaxel 80 mg/m(2) on days 1, 8, and 15 every 28 days. All patients were evaluable for efficacy and toxicity; a median of four cycles was administered. One patient (3%) showed a complete response (CR), nine patients (26%) had partial response, stable disease was observed in eight patients (23%) for a disease control rate (DCR) of 52%. The median time to progression (TTP) was 7.6 months (95% CI 3.2-10.7 months) with a median survival time (MST) of 12.6 months (95% CI 4.6-18.8 months). Toxicity was acceptable and manageable: no cases of febrile neutropenia occurred and only two patients (6%) developed grade 3 neuropathy. This is the first study that evaluated the role of anthracyclines in combination with paclitaxel as second-line chemotherapy in metastatic transitional cell carcinoma of the urothelium. Our findings show the substantial activity of weekly regimen of paclitaxel and epirubicin: due to its manageable profile of toxicity, this schedule could represent an interesting therapeutic option in previously treated patients with advanced urothelial carcinoma.     

A Phase II study of gemcitabine and docetaxel in patients with metastatic pancreatic carcinoma

BACKGROUND: Patients with metastatic pancreatic carcinoma have a poor survival. Chemotherapy with gemcitabine is the standard first-line treatment. In a Phase II trial at one academic cancer center, the clinical safety and activity of combining gemcitabine and docetaxel were assessed. METHODS: Patients with previously untreated, advanced pancreatic carcinoma were eligible. Bidimensionally measurable disease or evaluable disease with an elevated tumor marker, good performance status, and adequate organ function were required. Patients received docetaxel 60 mg/m(2) on Day 1 and gemcitabine 600 mg/m(2) on Days 1, 8, and 15 every 28 days. Ciprofloxacin was administered on Days 8-18. Dose attenuations were made as indicated for toxicity. Patients were restaged radiographically after every two cycles. RESULTS: Thirty-four patients were enrolled, and 33 patients were evaluable for response. There were 23 men and 10 women among the evaluable patients. The median age was 63 years, and all patients had an Eastern Cooperative Oncology Group performance status of 0 or 1. Three patients had received prior chemoradiation for postresection adjuvant therapy. One hundred forty-six cycles of chemotherapy were administered, and 5 cycles (3%) in 4 patients (12%) were complicated by febrile neutropenia. Twenty percent and 11% of patients on Day 8 and Day 15 doses of gemcitabine, respectively, were omitted for toxicity. The objective response rate was 18%, and the median survival was 8.9 months (95% confidence interval, 5.2-11.2 months). The 1-year survival rate was 29%. CONCLUSIONS: The combination of gemcitabine and docetaxel in patients with advanced pancreatic carcinoma is well tolerated and is associated with moderate activity despite aggressive dose reduction. Whether combination regimens are more effective than single agents in the treatment of patients with pancreatic carcinoma awaits evaluation in randomized studies.