Dose Rate Infusion Of Gemcitabine Research Articles

Retrospective analysis of fixed dose rate infusion of gemcitabine and S-1 combination therapy (FGS) as salvage chemotherapy in patients with gemcitabine-refractory advanced pancreatic cancer: inflammation-based prognostic score predicts survival.

The purpose of this study was to assess the efficacy and safety of fixed dose rate infusion of gemcitabine and S-1 combination therapy (FGS) in patients with gemcitabine (GEM)-refractory pancreatic cancer (PC) and to explore independent variables associated with survival. We retrospectively reviewed consecutive patients with GEM-refractory PC who received FGS at our institution from March 2009 to December 2013. GEM was administered by fixed dose rate intravenous infusion of 1,200mg/m(2) as a 120-min infusion on day 1, and S-1 was administered orally twice a day at a dose of 40mg/m(2) on days 1-7. Cycles were repeated every 14days. Sixty-one patients with GEM-refractory PC received FGS. Sixteen patients received FGS as third-line treatment. Twenty-nine patients (48%) had a history of S-1 administration. The objective response rate was 13%, and the disease control rate was 49%. The median progression-free survival time was 2.7months, and the median overall survival time was 6.0months. Major Grade 3 or 4 adverse events included neutropenia (15%), diarrhea (3%), anorexia (2%), and fatigue (2%). A high inflammation-based prognostic score (modified Glasgow prognostic score (mGPS), which incorporates C-reactive protein and albumin), a performance status >0, and serum carbohydrate antigen 19-9 level >2,000IU/ml were independently associated with a poor outcome. FGS might be effective and well tolerated as salvage chemotherapy in a practical setting. The inflammation-based prognostic score is a simple and reliable indicator of survival in the setting of salvage chemotherapy.

Fixed Dose Rate versus Standard Dose Rate Infusion of Gemcitabine and Cisplatin in Advanced Stage Non-Small Cell Lung Cancer

Background: Comparing the efficacy and safety of gemcitabine at a fixed-dose rate (FDR) infusion (10 mg/m2/min) with the standard dose rate infusion in patients with locally advanced and metastatic non-small squamous cell carcinoma (NSCLC). Methods: The study randomized 60 patients with confirmed diagnosis of NSCLC to receive gemcitabine at a dose of 1000 mg/m2 on days 1 and 8 given as a 30-min infusion (Arm A) or at a rate of 10 mg/m2/min (Arm B). Cisplatin 75 mg/m2 was administered intravenously on day 2 in both arms. Results: No difference in overall response rate (46.6% versus 43.3%). Median time to progression for Arm A was 7 months (95% CI, 6.207 - 7.793 months), versus 6 months for Arm B (95% CI, 4.990 - 7.010 months). Median survival time was comparable [12 months (95% CI, 8.588 - 15.412 months) versus 11 months (95% CI, 9.066 - 12.934 months)] respectively. Two-year survival (18% versus 11%, p = 0.38) was detected. No treatment related deaths occurred. Main hematological toxicities were grade I and II neutropenia, in 36.7% and 53.3% respectively (p = 0.044). Grade III anemia was observed in 10% and 6.7% in both arms respectively (p = 0.024). Grade I and II nausea and vomiting was observed in 50% and 46.7%. Conclusions: FDR gemcitabine in combination with cisplatin had equivalent efficacy and more severe hematologic toxicities compared to the standard 30-min gemcitabine infusion with cisplatin in patients with advanced NSCLC.

Efficacy and safety of fixed dose rate gemcitabine infusion in combination with docetaxel in patients with relapsed/refractory soft tissue sarcoma

To evaluate the efficacy and safety of fixed dose rate (FDR) gemcitabine infusion in combination with docetaxel in patients with relapsed/refractory soft tissue sarcoma. Clinicopathological data of 28 patients with relapsed/refractory soft tissue sarcoma treated in our hospital from April 2008 to August 2013 were reviewed in this study. The patients received 900 mg/m² gemcitabine with a FDR infusion (10 mg/m²/min) in a total dose of 900 mg/m² on days 1 and 8, and 75 mg/m² docetaxel intravenously over 60 min on day 8 of a 21-day cycle. When irradiation was conducted before drug therapy, the dose of gemcitabine was reduced to 675 mg/m² on days 1 and 8. The clinicopathological characteristics, short-term response, long-term survival status and toxicity were analyzed retrospectively. The 28 patients received a total of 118 cycles of therapy (range 1-8 cycles, median 4 cycles per patient). No patient achieved complete response (CR), 4 partial responses (PR) and 11 stable diseases (SD), with an overall response rate (ORR) of 14.3% and clinical benefit rate (CBR) of 53.6%. The median progression-free survival (PFS) was 3.2 months and the median overall survival (OS) was 8.5 months. PFS and OS were correlated with the response to this treatment regimen (P < 0.0001). Patients with clinical benefit had significantly better PFS and OS than the patients with progressive disease (P < 0.05 for all). The ORR, CBR, PFS and OS were better in patients with leiomyosarcoma than in patients with other histological subtypes in this study, but the differences were not significant (P > 0.05 for all). Grade 3-4 neutropenia, anemia and thrombocytopenia were 50.0%, 17.9% and 14.3%, respectively. Only one patient (3.6%) had febrile neutropenia. Grade 3 non-hematologic toxicities were nausea/vomiting (3.6%) and mucositis (3.6%). No grade 4 non-hematologic toxicities were observed. Almost all non-hematologic toxicities were grade 1-2 and manageable. The fixed dose rate (FDR) gemcitabine infusion in combination with docetaxel is an effective treatment regimen for patients with relapsed/refractory soft tissue sarcoma, and with tolerable adverse reactions.

Phase II study of a fixed dose-rate infusion of gemcitabine associated with erlotinib in advanced pancreatic cancer

To evaluate the feasibility, toxicity and efficacy of the combination regimen consisting of gemcitabine-FDR infusion plus erlotinib, in ACP patients. Forty-two patients with histologically confirmed, locally advanced or metastatic pancreatic cancer were included in this phase II trial. Main objectives were to assess the efficacy and safety of this regimen. Therapeutic regimen consisted of gemcitabine 1,200 mg/m(2) in 120-min infusion on days 1, 8 and 15, plus erlotinib 100 mg orally once daily. Cycles were repeated every 28 days. A total of 160 courses of gemcitabine-FDR erlotinib were administered (median 3.8 courses per patient). The most common grade 3-4 AEs were neutropenia (21%), thrombocytopenia (10%), skin rash (10%) and asthenia (10%). Complete response was achieved in one patient (2%) and 11 (26%) achieved a partial response. Stable disease and progression disease were observed in 11 patients (26%) and 19 (45%), respectively. Median time to progression was 5 months (95%CI: 3.9-5.8 months) and median overall survival was 8 months (95% CI: 5.1-10.8). One-year survival rate was 35%. A regimen consisting of gemcitabine-FDR infusion plus erlotinib is active and well tolerated in APC patients. However, the results do not justify the conduct of a Phase III trial.

Fixed dose rate infusion of gemcitabine and UFT combination chemotherapy in patients with advanced biliary cancer

e15581 Background: Biliary cancer is diagnosed at advanced stage and recurrence is common after surgical resection. Gemcitabine and UFT combination chemotherapy showed promising results in advanced pancreatic cancer(APC) and fixed dose- rate(FDR) infusion(10mg/m2/min) of gemcitabine is more effective than 30min-infusion in APC patients. We conducted a prospective multicenter phase II study to evaluate the efficacy and toxicity of FDR gemcitabine and UFT combination chemotherapy in advanced biliary cancer(ABC) patients. We evaluated the quality of life(QOL) and relationship between treatment outcome and polymorphisms of DNA repair gene such as RecQ1, RAD54L, XRCC1 and ATM. Methods: We included the chemo-naive patients with measurable metastatic or recurrent biliary adenocarcinoma except gall bladder cancer. Patients received gemcitabine infusion of rate of 10mg/m2/min on day 1, 8, and 15 plus oral UFT (400mg/m2) on day 1 to 21. We used modified PCR-RFLP method to evaluate the polymorphism of DNA repair gene. The primary endpoint was response rate. Results: From October 2006 to March 2008, 47 patients were enrolled and 33 of them were included in this analysis. Median age was 58 years(range 33–73 years) and 18 patients were male. Partial response was 24.2% and disease control rate was 51.5%. The estimated median time to progression(TTP) was 87 days(95% CI 51–123). Median overall survival was 243 days(95% CI 114–372). Grade 3/4 neutropenia was observed in 12 of 33 patients(36.4%) and 17 times of 114 cycles of chemotherapy(14.9%). No febrile neutropenia was observed. Grade 3/4 thrombocytopenia occurred in 5 patients(15.2%). Non-hematologic toxicities were mild. Polymorphism of XRCC1 was related to TTP(TTP of wild, heterozygous variant and homozygous variant type was 162, 71 and 25 days, respectively. p=0.0039). QOL as a secondary endpoint was not analyzed at this time. Conclusions: FDR infusion of gemcitabine and UFT combination chemotherapy in chemo-naïve patients with ABC is a well-tolerated and effective regimen. No significant financial relationships to disclose.

Fixed-dose rate infusion of gemcitabine and weekly cisplatin in elderly or poor performance status patients with unresectable non-small cell lung cancer

We investigated the efficacy and toxicity of a 4-week schedule of a fixed dose rate infusion of gemcitabine and weekly cisplatin in elderly or poor performance status patients with unresectable non-small cell lung cancer (NSCLC). In this study, 48 patients with previously untreated NSCLC were given combination chemotherapy that consisted of gemcitabine 1,000 mg/m(2) (10 mg/m(2)/min fixed dose rate infusion) and cisplatin 25 mg/m(2), and both drugs were given weekly on days 1, 8 and 15. A partial response and stable disease were observed in 20 patients (41.7%, 95% CI; 27.8-55.6%) and 12 patients (25.0%), respectively. The overall median survival was 10.30 months (range: 7.85-12.74 months). Major toxicities included neutropenia (grade 3 to 4, 29.2%) and infection (grade 3 to 4, 27.1%). Our results indicate that this regimen is a feasible treatment for elderly or poor performance status patients with unresectable NSCLC. Nevertheless, the morbidity due to myelosuppression and infection following this treatment should be carefully considered.

Prospective phase II trial of a combination of fixed dose rate infusion of gemcitabine with cisplatin and UFT as a first-line treatment in patients with advanced non-small-cell lung carcinoma

The standard chemotherapy for non-elderly patients with advanced non-small-cell lung cancer (NSCLC) is platinum-based doublet combination therapy. Preclinical and clinical evidence indicates that infusion at the fixed dose rate (FDR) of 10mg/(m(2)min) may be more effective than a standard 30-min infusion of gemcitabine. In addition, oral uracil-tegafur (UFT) was associated with a survival advantage in the adjuvant setting. Therefore, we performed a phase II study using the combination of gemcitabine, cisplatin and UFT as first-line therapy in patients with advanced NSCLC. Eligible patients had histologically or cytologically confirmed stage IIIB or IV NSCLC with a performance status of 0-2 and were chemotherapy-naive. Gemcitabine (1,250 mg/m(2), 10mg/(m(2)min) on days 1 and 8, respectively) and cisplatin (75 mg/m(2) on day 1) were injected intravenously and UFT (400mg/day) was administered orally on days 1-14. Treatment was repeated every 3 weeks for up to six cycles. Primary endpoint was overall response rate and secondary endpoints were overall survival, time to progression and safety profile. Thirty-seven patients were enrolled. The median age was 60 years (range: 44-72 years). The performance status was 0 in 4, 1 in 30, and 2 in 3 patients. Twenty-three patients completed six cycles. Complete response was achieved in one (3%) patient, partial response in 17 (46%) patients, and stable disease in 10 (27%) patients. The overall response rate was 48.6% on an intention-to-treat basis and 54.5% of patients in whom a response evaluation was possible (n=33). The median survival time was 14.7 months (95% confidence interval [CI] 11.2-18.2), the 1-year survival rate was 54% and the median time to progression was 5.4 months (95% CI 4.3-6.4). Toxicities were moderate and mostly hematological adverse events. Grade 3/4 neutropenia occurred in 37% of patients and four patients experienced febrile neutropenia. Grade 3/4 anemia and thrombocytopenia occurred in 19% and 5% of patients, respectively. Non-hematological toxicities were mild. The combination of gemcitabine, cisplatin and UFT is an active and well-tolerated first-line regimen in patients with advanced NSCLC.

Randomized Phase II Study of Gemcitabine and Docetaxel Compared With Gemcitabine Alone in Patients With Metastatic Soft Tissue Sarcomas: Results of Sarcoma Alliance for Research Through Collaboration Study 002

Gemcitabine as a single agent and the combination of gemcitabine and docetaxel have activity in patients with metastatic soft tissue sarcoma. To determine if the addition of docetaxel to gemcitabine improved clinical outcome of patients with metastatic soft tissue sarcomas, we compared a fixed dose rate infusion of gemcitabine versus a lower dose of gemcitabine with docetaxel. In this open-label phase II clinical trial, the primary end point was tumor response, defined as complete or partial response or stable disease lasting at least 24 weeks. A Bayesian adaptive randomization procedure was used to produce an imbalance in the randomization in favor of the superior treatment, accounting for treatment-subgroup interactions. One hundred nineteen of 122 randomly assigned patients had assessable outcomes. The adaptive randomization assigned 73 patients (60%) to gemcitabine-docetaxel and 49 patients (40%) to gemcitabine alone, indicating gemcitabine-docetaxel was superior. The objective Response Evaluation Criteria in Solid Tumors response rates were 16% (gemcitabine-docetaxel) and 8% (gemcitabine). Given the data, the posterior probabilities that gemcitabine-docetaxel was superior for progression-free and overall survival were 0.98 and 0.97, respectively. Median progression-free survival was 6.2 months for gemcitabine-docetaxel and 3.0 months for gemcitabine alone; median overall survival was 17.9 months for gemcitabine-docetaxel and 11.5 months for gemcitabine. The posterior probability that patients receiving gemcitabine-docetaxel had a shorter time to discontinuation for toxicity compared with gemcitabine alone was .999. Gemcitabine-docetaxel yielded superior progression-free and overall survival to gemcitabine alone, but with increased toxicity. Adaptive randomization is an effective method to reduce the number of patients receiving inferior therapy.

Phase II study of a fixed dose-rate infusion of gemcitabine associated with erlotinib in advanced pancreatic carcinoma

15013 Background: The efficacy of gemcitabine in pancreatic cancer can be improved by its combination with erlotinib. Likewise, a fixed dose-rate infusion of gemcitabine seems to be superior to the conventional 30-minute infusion. Our objective was to evaluate the efficacy and toxicity of a fixed dose-rate infusion of gemcitabine associated with erlotinib in patients with advanced adenocarcinoma of the pancreas. Methods: From May 2005 to October 2006, 21 chemotherapy-naïve patients were included, median age 62 years (range 47 - 78), male/female 12/9. Five patients (24%) had locally advanced disease and 16 (76%) distant metastases. The Karnofsky score was 80–100 in 11 (52%), and 60–70 in 10 (48%). Treatment consisted of gemcitabine 1200 mg/m2 given as a 120-minute infusion on days 1, 8, 15, plus erlotinib 100 mg p.o daily. Cycles were repeated every 4 weeks. Results: A total of 80 cycles of chemotherapy were delivered with a median of 3.8 per patient (range 1- 8). There were five partial responses (24%, 95% CI: 8.4 - 47.6%), whereas seven patients had stable disease (33%) and 9 had a progression (43%). The median time to progression was 4 months. After a median follow-up of 6 months (1–14 months), the median overall survival has not been achieved. Toxicity was low. Grade 3- 4 WHO toxicities per patient were as follows: neutropenia in 5 (24%), thrombocytopenia in 1 (5%) and anaemia in 3 (14%). Grade 1–2 rash appeared in 8 (38%) and grade 3 in 3 (14%). Four patients (19%) had diarrhoea grade 1–2. Conclusions: These preliminary results suggest that a fixed dose-rate infusion of gemcitabine associated with erlotinib is active and well tolerated in patients with advanced pancreatic carcinoma. No significant financial relationships to disclose.

Phase I trial of gefitinib with concurrent radiotherapy and fixed dose-rate gemcitabine infusion, in locally advanced pancreatic cancer

4105 Background: Pancreatic cancers are resistant to radiotherapy (RT) and current chemotherapy agents. Epidermal growth factor receptor (EGFR) is over-expressed in pancreatic cancer and in vitro studies have shown that EGFR inhibitors can overcome radio- and chemo-resistance. The aim of the study was to determine the maximally tolerated dose of gefitinib, in combination with RT and gemcitabine for patients with locally advanced pancreatic carcinoma (LAPC). Methods: Eighteen patients with pathological proven LAPC, due to major vascular invasion based on helical computed tomography and endoscopic ultrasound, were entered. The targeted irradiated volume included the tumor and 2 cm-margin. Prophylactic irradiation of regional nodes was not allowed. Patients with &gt;500 cc of planned tumor volume (PTV) were excluded. An initial cohort of 6 patients was treated with RT (45 Gy/25 fractions/5 weeks) plus concomitant gefitinib (250 mg/day). Successive cohorts of patients received 100, 150 and 200 mg/m2/day of gemcitabine in a 2 hour infusion over weeks 1,2,3,4, and 5 with gefitinib (250 mg/day) and RT. Gefitinib was continued after RT until progression. A pharmacodynamic study of angiogenic markers (VEGF and IL-8) was also performed. Results: Mean PTV was 293cc (range 137–462 cc). There were no dose-limiting toxicities on study. Common toxicities were mild neutropenia, asthenia, diarrhea, cutaneous rash and nausea/vomiting. One patient showed a partial response of 13 months in duration, and 7 patients showed disease stabilization. Median progression free survival (PFS) was 3.7 months and median overall survival (OS) was 7.5 months. No patients have a reduction in VEGF levels &gt;50%. Reduction in VEGF serum levels &gt;25% and IL-8 levels &gt;50% had no impact on PFS and OS. Conclusion: Our results support thatthe combination of gefitinib, RT and gemcitabine showed an acceptable toxicity but with modest activity in LAPC. [Table: see text]

Fixed dose-rate gemcitabine infusion as first-line treatment for advanced-stage carcinoma of the pancreas and biliary tree: series of 106 consecutive patients

14099 Background: Our group recently published a phase II trial of GEM infused at fixed dose-rate of 10 mg/m2/min over 100 min in patients with advanced PDAC and BTC. (Cancer September 15,2005). Given the promising results obtained in the first 40 pts, we expanded the cohort under an observational protocol and this is the report of such experience. Methods: From April 2002 to September 2005, 106 advanced PDAC (n = 75) or BTC (n = 31) pts (median age: 63 yrs, range 28–82; M/F: 48/58; PDAC/BTC: 75/31; LA/Met: 36/70; PS 0/1/2/3: 31/53/17/5) were treated with GEM 1000 mg/m2 at the fixed dose-rate of 10 mg/m2/min for 7 consecutive wks and weekly × 3 q4 wks thereafter (FDR-GEM). All patients and 1154 treatment weeks were evaluable for toxicity, 100 were evaluable for response, 87 patients were evaluable for clinical benefit response (CBR) according to Burris criteria, and 56 patients had elevated CA19.9 serum levels at entry. Results: From April 2002 to September 2005, 106 advanced PDAC (n = 75) or BTC (n = 31) pts (median age: 63 yrs, range 28–82; M/F: 48/58; PDAC/BTC: 75/31; LA/Met: 36/70; PS 0/1/2/3: 31/53/17/5) were treated with GEM 1000 mg/m2 at the fixed dose-rate of 10 mg/m2/min for 7 consecutive wks and weekly × 3 q4 wks thereafter (FDR-GEM). All patients and 1154 treatment weeks were evaluable for toxicity, 100 were evaluable for response, 87 patients were evaluable for clinical benefit response (CBR) according to Burris criteria, and 56 patients had elevated CA19.9 serum levels at entry. Conclusions: The results obtained with FDR-GEM in a series of 106 consecutive pts confirm previous results obtained in smaller series and suggest that pharmacokinetically rationale GEM scheduling may improve its therapeutic index. FDR-Gem may constitute a viable alternative to standard Gem infusion as first-line treatment in advanced PDAC and BTC. No significant financial relationships to disclose.

Phase I Study of Fixed Dose Rate Infusion of Gemcitabine in Patients with Unresectable Pancreatic Cancer

The purpose of this study was to determine the feasible dose of gemcitabine when administered as a fixed dose rate infusion (10 mg/m(2)/min) on a weekly schedule to Japanese patients with unresectable advanced pancreatic cancer. Patients were required to have histologically or cytologically proven locally advanced or metastatic pancreatic cancer for which they had received no previous chemotherapy. Gemcitabine was administered intravenously weekly for three consecutive weeks every 4 weeks. Patients at three dose levels were scheduled to receive escalating doses of gemcitabine: 1000 mg/m(2) over 100 min (Level 1), 1200 mg/m(2) over 120 min (Level 2) and 1500 mg/m(2) over 150 min (Level 3). A total of 16 patients were enrolled in this study between December 2003 and September 2004. Maximum-tolerated dose was not reached during the first course. Dose-limiting toxicity was Grade 4 neutropenia. Grade 3 or 4 neutropenia was observed at Level 3 in all six patients in the first course, and administration of gemcitabine on Day 8 or 15 was skipped in all six patients. Non-hematologic toxicity was mild and the most common symptoms were anorexia, nausea and vomiting. Partial response was achieved in 1 of the 17 patients (7%). Median overall survival was 7.3 months. Gemcitabine administered at a rate of 10 mg/m(2)/min was tolerated up to 1500 mg/m(2), but 1200 mg/m(2) represented a more appropriate recommended dose in further studies owing to neutropenia in Japanese patients with advanced pancreatic cancer.

Prolonged fixed dose rate infusion of gemcitabine with autologous haemopoietic support in advanced pancreatic adenocarcinoma

This study aimed to define the maximum-tolerated dose (MTD) of fixed dose rate (FDR) of gemcitabine (2′-2′-difluorodeoxycitidine) infusion with circulating haemopoietic progenitor support and to evaluate the activity of the treatment. Secondary end points were pharmacokinetic of gemcitabine and difluorodeoxyuridina (dFdU) measured at first course and the activity andexpression profile of cytidine deaminase (CdA) on circulating mononuclear cells. Patients with advanced pancreatic carcinoma received escalating dose of gemcitabine 10 mg m−2 min−1 every 2 weeks with circulating haemopoietic progenitor support. First dose level was 3000 mg m−2 and the doses were increased by 500 mg m−2 until MTD. In all, 23 patients were enrolled. Toxicities were mild or moderate; the only patient treated at 7000 mg m−2 died because of toxicity; therefore; the MTD was established at 6500 mg m−2. The overall response rate was 22.2%. The AUC of gemcitabine showed a dose-dependent increase, while the AUC of dFdU reached a plateau at 4500 mg m−2. A significant relationship was found between the AUC of dFdU and CdA expression and activity (P<0.05). Moreover, progression rate and survival were significantly related to CdA expression and activity levels. The activity of high-dose gemcitabine is not superior to that reported with less intensive FDR schedules. The predictive role of CdA expression and activity on outcome deserves further investigation.

Short Communication: The Efficacy of Fixed Dose Rate Infusion of Gemcitabine Combined with IFN-α2a in Patients with Advanced Refractory Renal Cell Carcinoma

The fixed dose rate (FDR) infusion of gemcitabine is based on pharmacokinetic studies demonstrating an increased peak concentration of gemcitabine-active metabolites inside the cell. In this prospective study, for the first time we investigated gemcitabine FDR infusion together with interferon-alpha2a (IFN-alpha) in pretreated patients with advanced renal cell carcinoma (RCC). Twelve patients received 800 mg/m2 gemcitabine (i.v. infusion of 10 mg/m2/min) on days 1 and 8 every 3 weeks, combined with 3.0 x 10(6) U s.c. IFN-alpha on days 1, 3, and 5 of each week. Median age of patients was 64 years, and the Eastern Cooperative Oncology Group performance status (ECOG PS) was 0-1 in 10 patients. All patients were pretreated, 5 with > or =2 lines of chemoimmunotherapy. A median number of five cycles of gemcitabine per patient were given, with a mean weekly dose intensity of 72% of that planned. Among 11 evaluable patients, 2 (18%) partial responses and 5 (46%) stable diseases (median duration of 9.3 months) were observed. Median time to progression (TTP) and overall survival were 7.1 months and 13.0 months, respectively. The most frequently occurring grade 3 or 4 adverse events were leukoneutropenia (25%), thrombocytopenia (17%), and diffuse edema (25%). One patient developed a cerebrovascular accident potentially related to treatment. These promising results with the combination of gemcitabine infused at FDR and IFN-alpha deserve further investigation.

Overview of bladder cancer trials in the Cancer and Leukemia Group B.

The Cancer and Leukemia Group B (CALGB) Genitourinary Committee has developed a broad range of clinical trials across most stages of bladder cancer. Recurrence rates of superficial bladder cancer after transurethral resection range from 50-70%. Although adjuvant bacillus Calmette-Guerin reduces the risk of disease recurrence or progression, only 30% of patients have long-term disease-free survival. Because the development of novel secondline agents is needed, the CALGB is evaluating the utility of intravesicle gemcitabine as well as an oral proapoptotic agent (CP-461). In patients with locally advanced disease with an increased risk of disease recurrence after cystectomy, a randomized trial of conventional chemotherapy versus sequential dose-dense therapy is under development. The gemcitabine/cisplatin combination has become a commonly used regimen for the treatment of advanced transitional cell carcinoma (TCC). The CALGB is undertaking a Phase II study that incorporates a fixed dose rate gemcitabine infusion in this regimen, together with a selective epidermal growth factor receptor tyrosine kinase inhibitor, Iressa (Astra Zeneca, Wilmington, DE). In patients with renal insufficiency, a regimen of carboplatin, gemcitabine, and Iressa is planned. Novel agents, including arsenic trioxide and trastuzumab (Herceptin; Genentech, Inc., South San Francisco, CA), are being evaluated as secondline therapy in patients with advanced TCC who have disease progression after frontline therapy.

A combination of a fixed dose rate infusion of gemcitabine associated to a bolus 5-fluorouracil in advanced pancreatic cancer, a report from the Italian Group for the Study of Digestive Tract Cancer (GISCAD)

Laboratory evidences suggest the possibility that an infusion rate of 10 mg/m2/min may be more effective than the standard 30-min infusion of Gemcitabine (GEM). Thirty-four patients with histologically verified locally unresectable and/or metastatic pancreatic carcinoma received GEM at the dose of 1,500 mg/m2 with an infusion rate of 10 mg/m2/min, associated to 5-fluorouracil (5-FU) at the dose of 600 mg/m2. Both drugs were administered weekly for two consecutive weeks out of every three weeks. One complete and five partial responses have been observed for an overall response rate of 17% (95% CI: 3%-27%). The time to progression was 3.7 months with a median survival of 5.7 months. A clinical benefit was obtained in 5 of 29 patients (17%). Grade 3-4 WHO toxicities included neutropenia (35%) and thrombocytopenia (10%). It is unlikely that a fixed dose rate infusion of GEM, at least with this dose, can improve palliation in comparison with the standard 30-min infusion schedule in advanced pancreatic cancer.