Safety Of Gemcitabine Research Articles

Efficacy and safety of gemcitabine, carboplatin, dexamethasone, and rituximab in patients with relapsed/refractory lymphoma: a prospective multi-center phase II study by the Puget Sound Oncology Consortium

We conducted a multi-center phase II trial of gemcitabine (G), carboplatin (C), dexamethasone (D), and rituximab (R) in order to examine its safety and efficacy as an outpatient salvage regimen for lymphoma. Fifty-one patients received 2–4 21-day cycles of G (1000 mg/m2, days 1 and 8), C (AUC = 5, day 1), D (40 mg, daily days 1–4), and R (375 mg/m2, day 8 for CD20-positive disease) and were evaluable for response. Characteristics included: median age 58 yeas (19–79 years), stage III/IV 88%, elevated LDH 33%, median prior therapies 2, prior stem cell transplant 12%, chemoresistant 62%, median prior remission duration 2.5 months. The overall and complete response rates were 67% (95% confidence interval [CI] 54–80%) and 31% (95% CI 19–44%), respectively, with activity seen in a broad variety of histologies. Responses occurred in 16 of 17 (94%, 95% CI 83–100%) transplant-eligible patients and 15 of 28 (54%, 95% CI 34–71%) with chemoresistant disease. The median CD34 yield in patients attempting peripheral blood stem cell (PBSC) collection following this regimen was 10.9 × 106 CD34+ cells/kg (range 5.0–24.1 × 106). Hematologic toxicity was common, but febrile neutropenia (2.5%) and grade 4 non-hematologic adverse events (n = 2) were rare, with no treatment-related deaths. GCD(R) is a safe and effective outpatient regimen for relapsed lymphoma, and successfully mobilizes PBSCs.

Gemcitabine as first-line chemotherapy in elderly patients with unresectable pancreatic carcinoma

Gemcitabine (GEM) is the key drug for the chemotherapy of unresectable pancreatic cancer. However, the efficacy and safety of GEM has not been established in elderly patients. We retrospectively examined the prognosis of elderly pancreatic cancer patients treated with GEM. Sixty-six patients with unresectable pancreatic cancer (pathologically identified) and no prior chemotherapy were divided into three groups. Group A: patients aged 70years or more who received standard GEM (1000mg/m(2)) on days 1, 8, and 15 and rest on day 21; Group B: patients less than 70years old who received standard GEM therapy; and Group C: patients under best supportive care. Median survival times (MSTs) (days) were 311 in group A (p<0.05 vs. group C), 292 in group B (p<0.05 vs. group C), and 127 in group C. Among the patients who received GEM, 23% patients in group A and 16% patients in group B obtained partial responses. The response rates and MSTs were similar in groups A and B, as well as in more aged (≥75years) patients. Bone marrow suppression was more frequently seen in elderly patients. Cox's hazard model in patients aged 70years or more revealed that GEM therapy reduced the hazard ratio for death (hazard ratio: 0.683, p=0.041). Chemotherapy with GEM appears to be effective and safe in elderly patients as well as in younger patients. Patients with unresectable pancreatic carcinoma should receive GEM therapy even if they are aged 70 or more, even if they are aged 75 or more.

Potential activity and safety of gemcitabine and oxaliplatin (GEMOX) in different histologic subtypes of advanced thyroid cancer.

e16011 Background: Patients with advanced, incurable thyroid cancer have few satisfactory therapeutic options. In this present study we assessed the activity and safety of the association of gemcitabine and oxaliplatin (gemox) in patients with different histology of advanced thyroid cancer refractory to I-131 treatment. Methods: Twelve patients with advanced thyroid cancer (4 papillary, 6 vesicular, and 2 mixed) were evaluated from our specialized hospital. All were refractory to I-131 treatment with a median age of 64 years. All patients received a combination of gemcitabine (1,000 mg/m2) + oxaliplatin (100 mg/m2) every two weeks until progression, limiting toxicity or a plained stop at 12 cycles. The response was evaluated by Response Evaluation Criteria in Solid Tumors after 4 cycles. Results: At this time, twelve patients were evaluated over our series. Complete and partial responses were observed in 1 and 5 patients respectively, yielding an ORR of 50%. Stable disease was reported in another 4 patients (33%). Objective responses were noted in 83 % (5 out of 6) vesicular subtypes. This combination was generally well tolerated, no grade IV toxicity was observed. The most common treatment-related adverse event being asthenia (n = 10 with 3 grade III), peripheral neuropathy (n=11 with 1 grade III), diarrhea (n=1), anemia (n=12), thrombopenia (n=5), neutropenia (n=4 with 1grade III). There was no toxic death related to the treatment. Conclusions: The GEMOX regimen remains effective and well tolerated in advanced differentiated thyroid cancer. thus, further evaluation of this new combination seems warranted and will be presented. No significant financial relationships to disclose.

Three-Year Follow-Up of Survival and Progression in a Phase II Trial of Gemcitabine Plus Carboplatin (Plus Trastuzumab in HER2+ Patients) in Metastatic Breast Cancer Patients.

Abstract Background: We have previously reported (Loesch, et al. Clin Breast Cancer, 2008) the efficacy and safety of gemcitabine and carboplatin with or without trastuzumab in patients with metastatic breast cancer. We now report time-to-progression (TTP) and overall survival (OS) after up to 3.5 years of extended follow-up.Patients and Methods: Patients were stratified into 3 groups at registration; Group 1: HER2 positive (+) regardless of prior taxane; Group 2: HER2 negative (–) and taxane naïve or remote (no taxanes within the past 2 years); and Group 3: HER2– and taxane pretreated. Women ≥18 years of age, with ECOG performance status 0-2, with RECIST-defined measurable disease, and either HER2– or HER2+ (3+ score) by immunohistochemistry or fluorescence in situ hybridization were enrolled. Treatment: Day 1 gemcitabine 1500 mg/m2 over 30 minutes followed by carboplatin AUC=2.5 repeated every 14 days up to Cycle 9. Group 1 also received trastuzumab 8 mg/kg in Cycle 1 followed by 4 mg/kg in Cycles 2-9, followed thereafter by 6 mg/kg every 21 days until progression or intolerable toxicity.Results: A total of 150 patients were registered (50, 51, and 49 in Groups 1, 2, and 3, respectively). Median follow-up for surviving patients, calculated from registration, was 31.3, 27.1, and 25.4 months, respectively. Median TTP (calculated as progression-free survival), was 7.2, 5.6, and 4.6 months, respectively. Median OS (range) has not been reached for Group 1 (range, 1.2-46.9); for Group 2 was 21.7 months (&amp;lt;1-44.3); and, for Group 3 was 11.9 months (&amp;lt;1-33.6). At 24-months, survival rates were 73.3%, 41.4%, and 20.5%, respectively; at 36-months, survival rates were 60.6%, 25.7%, and ≤8.3%, respectively. For Group 1 only, the remaining 3 responding patients were followed for 3.5 years, at which time they were relapse-free.Conclusions: Gemcitabine plus carboplatin with or without trastuzumab has been shown to be highly active in metastatic breast cancer. HER2+ patients receiving trastuzumab had the highest TTP and survival rates of all treatment groups. As expected, taxane-pretreated patients had shortened TTP and decreased OS rates compared to taxane-naïve patients.Research support was provided, in part, by Lilly USA, LLC; Indianapolis, IN. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2105.

Efficacy and safety of gemcitabine, oxaliplatin, and bevacizumab in advanced biliary-tract cancers and correlation of changes in 18-fluorodeoxyglucose PET with clinical outcome: a phase 2 study

Previous phase 2 studies have shown antitumour activity with gemcitabine and oxaliplatin (GEMOX) in patients with advanced biliary-tract cancers (BTCs). In this phase 2 study, we assessed the efficacy and safety of combined bevacizumab with GEMOX (GEMOX-B) in patients with advanced BTCs, and investigated how changes in 18-fluorodeoxyglucose ([(18)F]FDG)-PET correlate with clinical outcome. Patients with advanced measurable BTCs were given the following treatment on days 1 and 15 of a 28-day cycle: bevacizumab 10 mg/kg, followed by gemcitabine 1000 mg/m(2) (10 mg/m(2) per min) and oxaliplatin 85 mg/m(2) (2-h infusion). [(18)F]FDG-PET scans were obtained at baseline and after completion of the second cycle. The primary endpoint was progression-free survival (PFS). Efficacy and safety analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00361231. 35 patients were enrolled and evaluable for efficacy and toxicity. Median PFS was 7.0 months (95% CI 5.3-10.3), and PFS at 6 months was 63% (47-79), which was below the targeted rate of 70%. Grade 3-4 toxic effects included neutropenia (n=7), raised alanine aminotransferase concentrations (n=5), peripheral neuropathy (n=5), and hypertension (n=5). [(18)F]FDG-PET scans showed a significant decrease in maximum standardised uptake value (SUV(max)) after two cycles of treatment (5.72 [SD 2.01] at baseline; 3.73 [SD 1.88] after two cycles; p<0.0001). These changes were more pronounced in patients with partial response or stable disease than those with progressive disease (24 patients, -2.80 [SD 1.95] vs five patients, 1.41 [SD 3.13]; p=0.009). Change in SUV(max) was a significant predictor of PFS (HR 1.35, 1.14-1.60, p=0.0006) and overall survival (1.25, 1.05-1.50, p=0.01). GEMOX-B showed antitumour activity with tolerable safety in patients with advanced BTCs. Decreases in SUV(max) on [(18)F]FDG-PET scans after treatment were associated with disease control and increases in PFS and overall survival. Genentech Oncology and Sanofi-Aventis.

The effect and side effects of Gemcitabine plus Vinorelbine in patients with triple-negative metastatic breast cancer

Objective The aim of this study was to evaluate the anti-tumor activity and safety of Gemcitabine (GEM) combined with Vinorelbine (NVB) in patients with advanced TNABC after chemotherapy.

Multicenter, phase II study of gemcitabine and S-1 combination chemotherapy in patients with advanced biliary tract cancer

To evaluate the efficacy and safety of gemcitabine and S-1 combination chemotherapy in patients with advanced biliary tract cancer. Patients with a measurable lesion and no previous history of chemotherapy or radiotherapy were enrolled. Gemcitabine was administered intravenously at a dose of 1,000 mg/m(2) over 30 min on day 1 and 15, repeated every 4 weeks. S-1 was administered orally at a dose of 40 mg/m(2) b.i.d. on days 1-14. Tumor response was assessed every two cycles using Response Evaluation Criteria in Solid Tumors criteria. As much as 35 patients were enrolled between December 2006 and July 2008; 14 patients (40%) with gallbladder cancer and 14 (40%) with intrahepatic cholangiocarcinoma were included and 7 patients (20%) had received previous surgical resection. The overall response rate was 34.3% and the overall disease control rate was 82.9%. The median overall survival time was 11.6 months (95% CI, 7.3-15.6 months), and the median time to progression was 5.9 months (95% CI, 4.0-7.7 months). The grade 3/4 toxicities were leucopenia (23%), neutropenia (34%), anemia (20%), thrombocytopenia (6%) and anorexia (3%). Gemcitabine and S-1 combination chemotherapy has promising efficacy and good tolerability in patients with advanced biliary tract cancer.

Promising overall survival of patients with recurrent/metastatic squamous cell carcinoma of head and neck receiving gemcitabine plus cisplatin treatment: report of a multi-center phase II study

The efficacy and safety of gemcitabine in combination with cisplatin (GC) as the first-line treatment in patients with recurrent/metastatic (R/M) squamous cell carcinoma of head and neck (SCCHN) was examined. Patients with R/M SCCHN without prior treatment for their R/M disease were eligible and treated with gemcitabine 1,250 mg/m(2) on day 1, day 8 and cisplatin 80 mg/m(2) on day 8 every 21 days. Forty patients were enrolled from March 2004 to January 2006, and 30 were evaluable for treatment effectiveness and outcome. The median age of evaluable patients was 50 years and all patients were male. Partial response was observed in 9 (30%) and stable disease in 7 (23.3%) patients. The overall response rate and disease control rate was 30 and 53.3%, respectively. The major toxic effects were ≥grade 3 leukopenia and anemia (65 and 27.5%, respectively). With a follow-up of 72 months, the median time to progression (TTP) was 128 days (95% CI, 78-242) and median overall survival (OS) was 401 days (95% CI, 216 approximately not reached). This GC regimen demonstrates a good activity and a promising survival period in patients with R/M SCCHN.

Multicenter phase II study of gemcitabine (GEM) plus S-1 in patients (pts) with advanced biliary tract cancer (BTC)

e15516 Background: Pts with advanced BTC have a poor prognosis and no standard palliative chemotherapy has been defined. The purpose of this prospective multicenter phase II study was to evaluate the efficacy and safety of GEM plus S-1 combination therapy in pts with advanced BTC. Methods: Pts with advanced BTC, with at least one measurable lesion were eligible for this study. Other eligibility criteria included: no previous palliative chemotherapy, ECOG performance status ≤ 2, and adequate organ function. S-1 was given orally at a dose of 80mg/m2 daily from day 1 to day 14. GEM was given intravenously at a dose of 1,000mg/m2 over 30 min on day 1 and day 15, repeated every 4 weeks. Tumor response was the primary endpoint and was assessed according to RECIST every 8 weeks. Planned sample size was 35 according to Simon's two stage method. Results: 35pts were enrolled: median age 67; M/F (22/13); ECOG performance status 0/1/2 (16/18/1). The primary tumor site was; 14 pts in gallbladders, 14 pts in intrahepatic bile ducts, 6 pts in extrahepatic bile ducts, and 1 pt in Vater of papilla. Seven pts had previous surgical resection. Complete and partial responses were achieved in 2 and 9 pts, respectively. Eighteen pts had stable disease. Overall response rate was 31.4% and overall disease control rate was 82.9%. The median TTP was 6.1 months (95%CI, 4.0–8.1 months) and the overall survival was 11.7 months (95%CI, 7.3- months). The grade 3/4 toxicities were: neutropenia (31.4%), anemia (17.1%), thrombocytopenia (2.9%), anorexia (2.9%). No treatment-related deaths occurred during the study. Conclusions: GEM plus S- 1 combination therapy showed promising efficacy and good tolerability in pts with advanced BTC. No significant financial relationships to disclose.

A phase II study of gemcitabine in combination with oxaliplatin as first-line chemotherapy in patients with inoperable biliary tract cancer

The aim of this study is to investigate the efficacy and safety of gemcitabine and oxaliplatin combination chemotherapy as first-line therapy in patients with inoperable biliary tract cancer (BTC). The treatment of this non-randomized phase II study consisted of gemcitabine 1,000 mg/m(2) intravenously (i.v.) on day 1 and oxaliplatin 85 mg/m(2) i.v. on day 2 every 2 weeks until disease progression, unaccep toxicity or patients' refusal. From Sept 2006 to Oct 2007, 40 patients were enrolled. In the ITT analysis, the objective response rate was 15.0% and the disease control rate was 52.5%. The median overall survival (95% CI) was 8.5 months (6.4-10.7) and the time to progression was 4.2 months (0.5-7.9). For the 305 cycles, observed grade 3/4 toxicity was uncommon. Gemcitabine and dose adjusted oxaliplatin combination chemotherapy had moderate anti-tumor activity and was well tolerated as a first-line treatment for patients with inoperable BTC.

Gemcitabine, Etoposide, Cisplatin, and Dexamethasone in Patients With Refractory or Relapsed Non-Hodgkin's Lymphoma

Background/AimsTo date, an effective salvage chemotherapy regimen for the treatment of refractory or relapsing non-Hodgkin's lymphoma (NHL) has not been discovered. This study was conducted to evaluate the efficacy and safety of gemcitabine, etoposide, cisplatin, and dexamethasone in relapsed or refractory NHL patients.MethodsAll patients had histologically proven relapsed or refractory NHL. Treatments consisted of gemcitabine 700 mg/m2 by continuous i.v. on days 1 and 8; etoposide 40 mg/m2 by i.v. on days 1-4; cisplatin 60 mg/m2 by i.v. on day 1; or dexamethasone 40 mg by i.v. on days 1-4 (GEPD) every 21 days. The primary end point was the patient response rate following two cycles of treatment. After two cycles, stem cells were harvested using mobilizing regimens (ESHAP or GEPD plus filgrastim), and this was followed by autologous stem cell transplantation or four additional cycles of GEPD.ResultsBetween January 2005 and January 2006, 20 patients (13 males and 7 females) were enrolled in the study. The median age was 53 (range 16-75) years. The most common histology was diffuse large B-cell lymphoma (n=10). The median follow-up duration was 5.2 (range 1.0-16.0) months. After two cycles, the overall response rate was 50.0% (10/20), including two complete responses and eight partial responses. The dose-limiting toxicity was myelosuppression. Grade IV neutropenia and thrombocytopenia occurred in 13 (65.0%) and 6 patients (30.0%), respectively. The median number of CD34-positive cells collected was 6.0 (range, 2.8-11.6) ×106/kg. Of the 17 patients < 66 years of age, 4 (23.5%) proceeded to autologous stem cell transplantation.ConclusionsGEPD chemotherapy in patients with refractory or relapsed NHL was effective as a salvage therapy and helpful for stem cell harvest followed by autologous transplantation.

Clinical observation of gemcitabine plus carboplatin regimen in treatment of advanced non-small cell lung cancer in aged patients

Objective To evaluate the clinical effect and safety of gemcitabine plus carboplatin regimen in the treatment of advanced non-small cell lung cancer(NSCLC) in aged patients. Methods 110 cases of aged patients with NSCLC , were divided into GEM group and NVB group according to the patients options. GEM group received 1 000 mg/m2, GEM at day 1 and 8, and AUC 5 CBP at day 1. NVB group underwent the therapy of 2.5 mg/m2, NVB at day 1 and8,and 80 mg/m2 DDP at day 1 and 3. Both were treated with 21 days as a cycle. Results Overall re-sponse rate was 75.0% in GEM group and 72.0% in NVB group without significant difference( P>0.05). The medi-an survival time(MST) ,disease median response time(DPT) and one year survival rate were similar in two groups( P>0.05). The incidence of adverse reactions was significantly lower in GEM group than in NVB group ( P<0.05 ).Conclusion Gemcitabine plus carboplatin regimen is effective and safe in treatment of advanced non-small cell lung cancer in aged patients Key words: Careinoma,non-small cell lung; Gemcitabine; Carboplatin; Antineoplastic combined Chemothera-py protocols ; Aged

A Phase II Trial of Gemcitabine Plus Capecitabine for Metastatic Renal Cell Cancer Previously Treated With Immunotherapy and Targeted Agents

We assessed the clinical activity and safety of gemcitabine plus capecitabine in patients with metastatic renal cell cancer previously treated with immunotherapy. In this phase II trial patients received 1,000 mg/m(2) gemcitabine intravenously on days 1, 8 and 15, plus 830 mg/m(2) capecitabine orally twice daily on days 1 to 21 of 28-day cycles. The primary end point was progression-free survival time. Secondary end points included overall survival time, objective response rate and toxicity. Of 84 patients enrolled 83 were evaluable for response and toxicity. A total of 65 patients had intermediate or poor risk prognosis. Median progression-free survival and overall survival were 4.6 (95% CI 3.7-7.3) and 17.9 months (95% CI 13.2-23.6), respectively. There were 6 partial responses and 1 complete response (objective response rate 8.4% [95% CI 3.5-16.6]). Two patients remain in unmaintained remission close to 3 years from the initiation of gemcitabine plus capecitabine treatment. On multivariate analysis more than 3 disease sites were significantly associated with shorter progression-free survival and patients with thrombocytosis, more than 3 disease sites or anemia had a significantly increased risk of death. Adverse events occurring at least once in more than 5% of patients included grade 3 or greater neutropenia (83%), grade 2 or greater hand-foot syndrome (13%), grade 3 or greater thrombocytopenia (12%), grade 3 or greater thromboembolic events (8%), grade 3 or greater fatigue (8%) and grade 2 or greater mucositis (6%). At the doses and schedule tested gemcitabine plus capecitabine demonstrated modest clinical activity in metastatic renal cell cancer after cytokine failure and produced significant neutropenia. A modified gemcitabine plus capecitabine regimen may be evaluated in patients with metastatic renal cell cancer after failure of approved targeted therapies.

Gemcitabine plus conventional-dose epirubicin versus gemcitabine plus cisplatin as first-line chemotherapy for stage IIIB/IV non-small cell lung carcinoma—A randomized phase II trial

Epirubicin was effective for the treatment of non-small cell lung carcinoma (NSCLC). This study compared the efficacy and safety of gemcitabine plus conventional-dose epirubicin (GE) with gemcitabine-cisplatin (GC) as first-line chemotherapy for stage IIIB/IV NSCLC and evaluated the predictive value of nuclear expression of excision repair cross-complementing group 1 (ERCC1) and topoisomerase IIalpha (TopoIIalpha) on treatment outcome. Patients were randomized to GE (gemcitabine, 1000mg/m(2) on days 1, 8, and 15 and epirubicin, 70mg/m(2) on day 15) or GC (gemcitabine, 1000mg/m(2) on days 1, 8, and 15 and cisplatin, 80mg/m(2) on day 15). Treatment cycles were repeated every 4 weeks. Immunohistochemical study of ERCC1 and TopoIIalpha was done for patients with available tumor specimens. The response rate was 31.0% (95% CI 16.4-45.5%) for GC (n=41) and 37.2.0% (95% CI 22.2-52.3%) for GE (n=39). No significant differences in median time-to-treatment-failure (TTF) (GC, 6.1 months; GE, 6.2 months) or overall survival (GC, 13.2 months; GE, 21.5 months) were found between the two arms. Grade 3/4 neutropenia and febrile neutropenia were more common in GE. However, delay of protocol treatment due to leukopenia was similar between the two arms. Patients with expression of both ERCC1 and TopoIIalpha had a significantly shorter TTF (median 2.4 months, 95% CI 0.7-4.1 months) than other patients (median 8.8 months, 95% CI 5.8-11.8 months) (p=0.04). GE regimen is effective and well-tolerated for NSCLC patients. Expression of both ERCC1 and TopoIIalpha may be associated with poor response to chemotherapy.

Trastuzumab and gemcitabine as salvage therapy in heavily pre-treated patients with metastatic breast cancer

In Her2-postive metastatic breast carcinoma, first-line trastuzumab-based therapy is well established; many centres continue antibody treatment beyond disease progression. In this trial, we evaluated the efficacy and safety of gemcitabine and trastuzumab after earlier exposure to anthracyclines, docetaxel and/or vinorelbine, and trastuzumab. Twenty-nine consecutive patients were included as eligible. Patients received gemcitabine at a dose of 1,250 mg/m2 on day one and eight, every 21 days. Trastuzumab was administered in three-week cycles. Clinical benefit rate (CBR; CR + PR + SD > or = 6 months) was defined as primary endpoint. As of July 2007, all patients are evaluable for toxicity, and 26 for response. Earlier therapies consisted of trastuzumab (100%), anthracyclines (100%), vinorelbine (96.6%), docetaxel (72.4%), and capecitabine (72.4%). 19.2% of patients experienced PR, and SD > or = 6 months was observed in a further 26.9%, resulting in a CBR of 46.2%. Time to progression was median 3 months, and overall survival 17 months. Neutropenia (20.7%), thrombocytopenia (13.8%), and nausea (3.4%) were the only treatment-related adverse events that occurred with grade 3 or 4 intensity. Four patients (13.8%) developed brain metastases while on therapy. While CBR was low when compared to trastuzumab-based first-line therapy, it is higher than what would be expected from gemcitabine monotherapy in a similar setting. Together with the favourable toxicity profile, this regimen appears to be a safe and potentially effective salvage therapy option in a heavily pre-treated population.

P3-107: Safety of gemcitabine and carboplatin plus bevacizumab for advanced stage non–small cell lung cancer (NSCLC): pooled preliminary safety data from two ongoing studies

P3-107: Safety of gemcitabine and carboplatin plus bevacizumab for advanced stage non–small cell lung cancer (NSCLC): pooled preliminary safety data from two ongoing studies

Gemcitabine and docetaxel combination regimen in metastatic breast cancer (MBC)

1107 Background: No standart chemotherapy regimen has been estabilished for the treatment of patients with metastatic breast cancer. The gemcitabine and docetaxel combination has been shown to be synergistic . This study is conducted to verify the clinical efficacy and safety of gemcitabine and docetaxel combination therapy in metastatic breast cancer. Methods: 27 metastatic breast cancer patients were treated with gemcitabine-docetaxel combination . Gemcitabine 1,250 mg/m2 IV infusion, on day 1 and 8, and docetaxel 70 mg/m2 on day 1 in 21 day cycles. 4–6 cycles of chemotherapy were repeated every 3 weeks. The primary endpoint was response rate, and survival. Results: The median age was 50 years (range,32–77). Performans status (ECOG) was 0–1. Hormone receptor status: ER+/ER-; 11/16, PR+/PR-; 14/13. Menopausal status were: 11 premenopausal, 16 postmenopausal. Of the 27 evaluable patients, there were 11 (40.7%) partial responses and no complete response. Overall response rate was 40.7%. Median time to progression was 7 months, and median survival was 14 months. Toxicities included grade 3–4 neutropenia in 9 (30%), thrombocytopenia in 6 (22%), anemia in 3(9%). There were no treatment releated deaths Conclusions: The combination of gemcitabine and docetaxel has shown favorable toxicity profile and promising activity in metastatic breast cancer patients. No significant financial relationships to disclose.

Gemcitabine plus conventional-dose epirubicin versus gemcitabine plus cisplatin as first-line chemotherapy for stage IIIB/IV non-small cell lung carcinoma: A randomized phase II trial

18072 Background: Epirubicin is active for treatment of non-small cell lung carcinoma (NSCLC) but its optimal dose was undetermined. This study was designed to evaluate the efficacy and safety of gemcitabine plus conventional-dose epirubicin for stage IIIB/IV NSCLC. Methods: Patients with histological or cytological diagnosis of stage IIIB/IV NSCLC who had not received prior chemotherapy were eligible. Patients were randomized to GE (gemcitabine, 1,000 mg/m2 on days 1, 8, and 15 and epirubicin, 70 mg/m2 on day 15) or GC (gemcitabine, 1,000 mg/m2 on days 1, 8, and 15 and cisplatin, 80 mg/m2 on day 15). Treatment cycles were repeated every 4 weeks. Objective tumor response and toxicity were evaluated by using the World Health Organization criteria. Results: No significant difference in baseline characteristics between patients randomized to GC (n=41) and GE (n=39) arms were found. The objective response rate was 31.0% (95% C.I. 16.4% to 45.5) for GC and 37.2.0% (95% C.I. 22.2% to 52.3%) for GE. The median time-to-treatment-failure and overall survival were 6.1 months (95% C.I. 4.9 to 7.4 months) and 13.2 months (95% C.I. 8.9 to 17.5 months) for GC and 6.2 months (95% C.I. 5.2 to 7.2 months) and 21.2 months (95% C.I. 14.6 to 27.8 months) for GE, respectively. More grade 3/4 neutropenia (71.8%) was noted in GE than in GC (43.9%). Febrile neutropenia was also more common in GE (4 patients) than in GC (1 patient). However, delay of protocol treatment due to leukopenia was similar between the 2 arms. Data on the expresssion of the excission repair cross-complimentation 1 (ERCC1), evaluated by immunohistochemical study for patients with available tumor tissue, will be presented. Conclusions: Gemcitabine plus conventional-dose epirubicin is an effective and well-tolerated regimen for patients with stage IIIB/IV NSCLC. No significant financial relationships to disclose.

Phase II trial of gemcitabine and irinotecan in previously treated patients with small-cell lung cancer

7718 Background: Gemcitabine and irinotecan has been shown to have an antitumor activity as a single agent against previously treated SCLC. The objective of this study was to assess the efficacy and safety of gemcitabine combined with irinotecan in patients with refractory or relapsed SCLC. Methods: Patients with histologically or cytologically confirmed SCLC, 20 to 74 years in age, performance status 0–2, with a history of receiving one platinum-based chemotherapy were eligible for the study. Treatment consisted of gemcitabine (1,000 mg/m2) and irinotecan (150 mg/m2) on days 1 and 15 of a 28-day cycle.The primary endpoint was the response rate (RR), and planned sample size for this phase II study was 30 patients (Simon's two-stage minimax design). Results: Thirty-one patients were enrolled and 30 patients (24 males/6 females, 10 refractory/20 sensitive, median age, 65 years) receive protocol treatment in this phase II trial. The median treatment cycles were 3 (1–10). The overall response rates was obtained in 39.3% (95% CI: 18.1% to 60.5%) of the patients, including two patients with refractory disease and 9 patients with sensitive disease. The median overall survival time was 14.4 months, and the 1-year survival rate was 51%. The median survival time of the patients with refractory disease was 7.4 months, compared with 14.4 months for patients with sensitive disease. The chief grade 3/4 toxicities included neutropenia (42%), thrombocytopenia (3%), diarrhea (9%), and liver dysfunction (3%). The only grade 4 toxicities were one case of grade 4 neutropenia (3.3%) and one case of grade 4 thrombocytopenia (3.3%). Conclusion: Gemcitabine plus irinotecan is an active regimen that seems to be well- tolerated by patients with previously treated SCLC. No significant financial relationships to disclose.

A randomized phase II trial of adjuvant chemotherapy with uracil / tegafur (UFT) and gemcitabine (GEM) vs. gemcitabine alone in patients with resected pancreatic cancer

4542 Background: GEM is now the standard therapy for patients with advanced pancreatic cancer (PC). However, there have been few randomized studies of adjuvant chemotherapy with GEM in patients with resected PC. Methods: Patients with invasive ductal pancreatic cancer who underwent radical surgery were enrolled. Within 8weeks after operation, pts were randomized to receive UFT and GEM (GU) or GEM alone (G). GEM was administrated at a dosage of 1g/m2 IV weekly X3 out of 4weeks and UFT at a dosage of 200mg/body/day orally continuously. Eligibility included histological residual tumor (R) 0 or 1, and no previous chemo- or/and radiation therapy. Primary endpoint was 1y disease free survival (DFS) rate and secondary endpoints included overall survival (OS) and side effects in both groups. Results: Between 05/02 and 12/05, 100 patients were randomized into the two arms of the trial (50 pts to GU and 50 to G). No pts were found to be ineligible. Pts characteristics were well balanced (GU/G) with regard to median age (62/63y), tumor status (T3+4 88/94%), nodal status (N positive 77/72%), histological residual tumor status (R0 76/68%). Until 03/06, 1y DFS rate was 50.3% in GU and 45.5% in G and there was no significant difference between two groups. The median OS was 20m in GU and 28m in G (Log rank test: N.S.). Grade 2 or more toxicities were observed in 67.3% of GU pts and 56.3% of G pts (N.S.). No grade 4 or more toxicity was observed in either groups. Leucocytopenia was the most frequently observed side effect in both groups (Grade 2 or more GU/G 49/46%). Conclusion: Preliminary results confirm the efficacy and safety of GEM based adjuvant chemotherapy for pts with resected PC, but addition of UFT with GEM dose not improve DFS as compared with GEM alone, so far. Final results will be presented at the meeting. No significant financial relationships to disclose.