A multicentre randomised phase II study of carboplatin in combination with gemcitabine at standard rate or fixed dose rate infusion in patients with advanced stage non-small-cell lung cancer.

BACKGROUND: Intracellular gemcitabine triphosphate (dFdCTP) levels can be optimised by administering gemcitabine at a fixed dose rate infusion. PATIENTS AND METHODS: Patients with chemonaive advanced non-small cell lung cancer (NSCLC) were randomised to receive gemcitabine at a fixed dose rate gemcitabine 750 mg/m(2) over 75 min (arm A) or gemcitabine 1000 mg/m(2) over 30 min (arm B) on days 1 and 8 every three week cycle. Carboplatin at AUC of 5 was administered in both treatment arms on day 1 of each cycle. End points were activity, tolerability and pharmacokinetics of plasma and intracellular gemcitabine. RESULTS: 76 patients were randomised. Response rate was 34% in arm A and 42% in arm B. Toxicity and quality of life scores were similar for both treatment arms. Mean plasma Cmax(gemcitabine) and mean dFdCTP AUC in arm A was 20.8 microM +/- 17.2 microM and 35,079 +/- 18,216 microM*min respectively and in arm B, 41.2 +/- 13.9 microM and 32 249 +/- 11 267 microM*min respectively. dFdCTP saturation was reached in Arm B but not in Arm A. CONCLUSION: The saturability of dFdCTP accumulation in Arm A suggests optimal delivery of gemcitabine is achieved using fixed rate infusion compared to 30-min infusion. Fixed dose rate gemcitabine is active and feasible, supporting the concept of fixed dosing rate of gemcitabine in advanced NSCLC. However, this entails a longer infusion time with associated higher costs involved.     

Three-arm randomized study of two cisplatin-based regimens and paclitaxel plus gemcitabine in advanced non-small-cell lung cancer: a phase III trial of the European Organization for Research and Treatment of Cancer Lung Cancer Group--EORTC 08975.

PURPOSE: To compare the therapeutic efficacy of paclitaxel plus cisplatin (arm A) versus gemcitabine plus cisplatin (arm B) and arm A versus paclitaxel plus gemcitabine (arm C) in chemotherapy-naive patients with advanced non-small-cell lung cancer (NSCLC).Materials and METHODS: Patients were randomly assigned to receive either paclitaxel 175 mg/m2 (3-hour infusion, day 1) or gemcitabine 1,250 mg/m2 (days 1 and 8) both combined with cisplatin 80 mg/m2 (day 1) or paclitaxel 175 mg/m2 (3-hour infusion, day 1) combined with gemcitabine 1,250 mg/m2 (days 1 and 8). Primary end point was comparison of overall survival for B versus A and C versus A. Secondary end points included response rate and duration, progression-free survival, toxicities, quality of life [QoL], and cost of treatment. RESULTS: Four hundred eighty patients (arm A, 159; arm B, 160; arm C, 161 patients) were enrolled; all baseline characteristics were balanced. Median survival times were as follows: arm A, 8.1 months; arm B, 8.9 months; arm C, 6.7 months. Response rates were 31.8% for arm A, 36.6% for arm B, and 27.7% for arm C. Other than myelosuppression (B v A, P <.005), no statistically or clinically significant differences were observed for secondary end points. The average treatment costs were 25% higher in arm C as compared with arms A and B. CONCLUSION: Gemcitabine plus cisplatin and paclitaxel plus gemcitabine do not increase overall survival in patients with advanced NSCLC as compared with paclitaxel plus cisplatin. Treatment was well tolerated, and most QoL parameters were similar, but costs associated with the nonplatinum arm were highest.     

Gemcitabine administered as a short infusion versus a fixed dose rate in combination with cisplatin for the treatment of patients with advanced non-small cell lung cancer

Previous studies have indicated that, in combination with cisplatin, fixed dose rate gemcitabine may be more efficacious than standard infusion gemcitabine. This open-label, randomised phase II study was aimed to compare the efficacy and safety of these regimens as treatment for advanced non-small cell lung cancer (NSCLC) in Latin American patients. Sixty-four patients were randomised to receive up to six cycles of treatment with cisplatin 75 mg/m(2) on Day 1 plus either gemcitabine 1000 mg/m(2) over 30 min on Days 1 and 8 of a 21-day cycle (standard arm, N=33) or gemcitabine 1000 mg/m(2) at a fixed dose rate of 10 mg/m(2)/min on Days 1 and 8 of a 21-day cycle (FDR arm, N=31). In the standard arm, 9 of 33 (27%) patients responded compared with 6 of 30 (20%) patients in the FDR arm (odds ratio: 0.67, 95% CI, 0.21-2.2; p=0.56). Median overall survival was 7.5 months in the standard arm and 9.9 months in the FDR arm. One-year survival rates were 35% and 37% in the standard arm and the FDR arm, respectively. Patients in the FDR arm experienced more grade 3/4 haematological toxicity than those in the standard arm (48% versus 21%). The results of this trial do not support FDR administration of gemcitabine in preference to the standard administration in Latin American patients with NSCLC.     

低剂量持续静脉滴注吉西他滨一线治疗晚期非小细胞肺癌的临床研究

背景与目的:目前已将吉西他滨联合顺铂作为晚期非小细胞肺癌的一线化疗方案,吉西他滨的常规使用剂量和方法是1000mg/m2半小时静脉滴注,第1、8天,每3周为一个疗程。本研究旨在评价低剂量吉西他滨持续6h静脉滴注联合顺铂一线治疗晚期非小细胞肺癌的有效性和安全性。方法:48例经病理和/或细胞学检查确诊、未经化疗的晚期非小细胞肺癌患者,采用吉西他滨250mg/m2持续静脉滴注6h,第1、8天,顺铂75mg/m2,每3周为一疗程,连续使用2疗程以上。结果:48例患者中46例可评价疗效,所有患者可评价不良反应。完全缓解率2.2%,部分缓解率30.3%,总有效率为32.5%,中位治疗至进展时间为5.1个月,中位生存时间为10.2个月,1年生存率36.6%。白细胞减少发生率为60.4%,血小板减少发生率为39.5%,Ⅲ～Ⅳ度的白细胞和血小板减少发生率分别为20.8%和12.5%。结论:低剂量吉西他滨持续6h静脉滴注联合顺铂一线治疗晚期非小细胞肺癌疗效确切、不良反应轻。     

A randomized phase II trial evaluating standard (50 mg/min) versus low (10 mg/min) infusion duration of gemcitabine as first-line treatment in advanced non-small-cell lung cancer patients who are not eligible for platinum-based chemotherapy

PURPOSE: Gemcitabine is one of the most active drugs against non-small-cell lung cancer (NSCLC). Preclinical data suggested that gemcitabine efficacy could be improved by increasing the dose or by increasing the infusion duration. This study has been designed in order to explore two different approaches of gemcitabine dose intensification in patients with advanced NSCLC. PATIENTS AND METHODS: A total of 121 chemonaive patients with locally advanced or metastatic NSCLC not suitable for a platinum-based chemotherapy were randomly allocated to chemotherapy with gemcitabine 1500 mg/m2 on days 1 and 8 every 3 weeks by standard 30 min intravenous infusion (arm A), or gemcitabine 10 mg/m2/min for 150 min on days 1 and 8 every 3 weeks by intravenous infusion at fixed dose rate (arm B). RESULTS: One hundred and seventeen patients were fully analyzed. No difference in response rate (16.1% versus 9.9%, p=0.28), median time to disease progression (4 months versus 4.5 months, p=0.34) median survival (9.8 months in both arms), and 1-year survival (42.6% versus 39.0% p=0.98) was detected in arms A and B, respectively. No treatment-related deaths occurred. Main hematological toxicities were grade 3-4 neutropenia observed in 17.9% of patients in group A and in 49.2% of individuals in group B (p=0.0002). The incidence of febrile neutropenia was 3.3% in arm A and 0% in arm B (p=0.17). Grade 3-4 thrombocytopenia was more frequently observed in arm B patients (9.9% versus 1.8%, p=0.057). Non-hematological toxicity was similar in both arms, and consisted in grade 1-2 gastrointestinal toxicity observed in 48.2% of patients in arm A and 41.0% in arm B. CONCLUSION: Intensification of standard doses or prolonged infusion schedule did not result in efficacy improvement. Gemcitabine infusion duration does not warrant further investigation in patients with advanced NSCLC.     

A randomized study comparing two different schedules of administration of cisplatin in combination with gemcitabine in advanced nonsmall cell lung carcinoma

BACKGROUND: This randomized trial was designed to investigate the feasibility, toxicity, and activity of two different schedules of gemcitabine plus cisplatin in previously untreated patients with advanced (International Union Against Cancer (UICC) Stage IIIB-IV) nonsmall cell lung carcinoma (NSCLC). METHODS: From February 1997 to September 1998, 82 patients with advanced NSCLC were entered onto the study and were randomized to gemcitabine 1000 mg/m(2) on Days 1, 8, and 15 plus cisplatin 80 mg/m(2) on Day 2 (arm A) or Day 15 (arm B) every 28 days. RESULTS: All the patients were assessable for toxicity (arm A/arm B: 151/177 cycles; median, 4 of 5 cycles per patient), and the following Grade 3-4 toxicities were reported (percentage of cycles in arm A vs. arm B): anemia, 7.9% and 2.3% (P < 0.05); leukopenia, 6.0% and 6.7%; thrombocytopenia, 15.0% and 1.6% (P < 0.01); no World Health Organization (WHO) Grade 3-4 nonhematologic toxicities were observed. These side effects led to gemcitabine dose reductions in 35.1% of courses in arm A and 22.0% of courses in arm B (P < 0.05) and to gemcitabine omissions in 28.5% of courses in arm A versus 7.3% of courses in arm B (P < 0.01). Dose intensities (DIs) of gemcitabine were 607.5 mg/m(2)/week in arm A and 711.6 mg/m(2)/week in arm B (P < 0.01); DIs of cisplatin were 18. 1 mg/m(2)/week in arm A and 18.8 mg/m(2)/week in arm B. The total delivered doses of gemcitabine were 9315.5 mg/m(2) in arm A and 12, 631.0 mg/m(2) in arm B (P < 0.01); the total delivered doses of cisplatin were 277.1 mg/m(2) in arm A and 333.0 mg/m(2) in arm B (P < 0.01). Response rates according to intention to treat were 40.4% (95% confidence interval [CI], 25.5-55.3) in arm A and 45% (95% CI, 29.5-60.5) in arm B. The overall median duration of response was 7.4 months; the median time to disease progression was 6 months (95% CI, 3-9) in arm A and 9 months (95% CI, 4-14) in arm B (P < 0.02); the median overall survival was 10 months (95% CI, 7.0-12.5) in arm A and 17 months (95% CI, 13.0-21.6) in arm B (P < 0.01); the 1-year survival rates were 34% and 63%, respectively. CONCLUSIONS: Our data show that arm B (cisplatin on Day 15) is less toxic than arm A (cisplatin on Day 2) and allows the administration of significantly higher total doses and dose intensities of chemotherapy. No significant differences in response rates were observed between the two schedules; patients on arm B experienced a significantly more prolonged progression free and overall survival; however, the study was not powered to detect differences in these outcomes.     

Phase III trial of gemcitabine plus cisplatin versus cisplatin alone in patients with locally advanced or metastatic non-small-cell lung cancer.

PURPOSE: The Hoosier Oncology Group has previously reported the results of its phase II trial of the combination of cisplatin plus gemcitabine. In that study of 27 assessable patients with advanced or metastatic non-small-cell lung cancer (NSCLC), the response rate was 33%, with a median survival of 8.4 months. Based on such favorable results, the Hoosier Oncology Group designed this randomized phase III study of gemcitabine plus cisplatin compared with cisplatin alone in chemotherapy-naive patients with advanced NSCLC. PATIENTS AND METHODS: Patients were randomized to receive either cisplatin (100 mg/m(2) intravenously on day 1 of a 28-day cycle) or the combination of cisplatin (100 mg/m(2) intravenously on day 1) plus gemcitabine (1,000 mg/m(2) administered intravenously on days 1, 8, and 15 of a 28-day cycle). RESULTS: From August 1995 to February 1997, 522 assessable chemotherapy-naive patients were randomized. Toxicity was predominantly hematologic and was more pronounced in the combination arm, with grade 4 neutropenia occurring in 35.3% of patients compared with 1.2% of patients on the cisplatin monotherapy arm. The incidence of neutropenic fevers was less than 5% in both arms. Grade 4 thrombocytopenia occurred in 25. 4% of patients on the combination arm compared with 0.8% of patients on the cisplatin monotherapy arm. No serious hemorrhagic events related to thrombocytopenia were reported for either arm. The combination of gemcitabine plus cisplatin demonstrated a significant improvement over single-agent cisplatin with regard to response rate (30.4% compared with 11.1%, respectively; P <.0001), median time to progressive disease (5.6 months compared with 3.7 months, respectively; P =.0013), and overall survival (9.1 months compared with 7.6 months, respectively; P =.004). CONCLUSIONS: For the first-line treatment of NSCLC, the regimen of gemcitabine plus cisplatin is superior to cisplatin alone in terms of response rate, time to disease progression, and overall survival.     

Randomized phase II study of gemcitabine plus cisplatin versus etoposide plus cisplatin for the treatment of locally advanced or metastatic non-small cell lung cancer: Korean Cancer Study Group experience

BACKGROUND: Several randomized trials have demonstrated superior response rates and survivals for new agent platinum doublets than for older platinum doublets in advanced non-small cell lung cancer (NSCLC), however, few trials have been performed in Asian populations. Thus, we conducted a randomized study to compare gemcitabine-cisplatin (GP) with etoposide-cisplatin (EP) in Korean patients with advanced NSCLC. METHODS: Patients with histologically confirmed, locally advanced or metastatic NSCLC were randomized to receive either gemcitabine 1250 mg/m2 on days 1 and 8 plus cisplatin 75 mg/m2 on day 1, or etoposide 100 mg/m2 on days 1-3 plus cisplatin 75 mg/m2 on day 1. Treatment was repeated every 21 days in both groups. The primary endpoint was response rate. RESULTS: Between May 2000 and December 2001, 83 patients at 9 Korean centers were enrolled in this study. The GP arm showed a significantly higher response rate (52.6% versus 19.4%; P = 0.002), a longer time to progression (4.3 months in both arms; P = 0.018) and a marginally significant prolongation of overall survival (18.3 months versus 10.9 months; P = 0.059) than the EP arm. Grades 3 and 4 thrombocytopenia (18% versus 0%) was more common in the GP arm whereas grades 3 and 4 neutropenia was more common in EP arm (48.7% versus 71.8%). Other toxicities were comparable in both arms. CONCLUSION: GP provided a significantly higher response rate and a longer time to progression than EP and should be considered a standard treatment in advanced NSCLC in Korean population.     

Docetaxel plus gemcitabine or docetaxel plus cisplatin in advanced pancreatic carcinoma: randomized phase II study 40984 of the European Organisation for Research and Treatment of Cancer Gastrointestinal Group.

PURPOSE: To define the efficacy and toxicity of docetaxel plus gemcitabine or docetaxel plus cisplatin for advanced pancreatic carcinoma. PATIENTS AND METHODS: Chemotherapy-naive patients with measurable disease and WHO performance status less than 2 were randomly assigned to receive 21-day cycles of gemcitabine 800 mg/m2 on days 1 and 8 plus docetaxel 85 mg/m2 on day 8 (arm A) or docetaxel 75 mg/m2 on day 1 plus cisplatin 75 mg/m2 on day 1 (arm B). Primary end points were tumor response and rate of febrile neutropenia grade. RESULTS: Of 96 randomly assigned patients (49 patients in arm A and 47 patients in arm B), 70 patients were analyzed for response (36 in arm A and 34 in arm B) and 89 patients were analyzed for safety (45 in arm A and 44 in arm B). Confirmed responses were observed in 19.4% (95% CI, 8.2% to 36.0%) of patients in arm A and 23.5% (95% CI, 10.7% to 41.2%) in arm B. In arm A, the median progression-free survival (PFS) was 3.9 months (95% CI, 3.0 to 4.7 months), median survival was 7.4 months (95% CI, 5.6 to 11.0 months), and 1-year survival was 30%. In arm B, the median PFS was 2.8 months (95% CI, 2.6 to 4.6 months), median survival was 7.1 months (95% CI, 4.8 to 8.7 months), and 1-year survival was 16%. Febrile neutropenia occurred in 9% and 16% of patients in arms A and B, respectively. CONCLUSION: Both regimens are well tolerated and show activity in advanced pancreatic carcinoma. The safety profile and survival analyses favor docetaxel plus gemcitabine for further evaluation.     

Single-agent gemcitabine: an active and better tolerated alternative to standard cisplatin-based chemotherapy in locally advanced or metastatic non-small cell lung cancer

This randomized study was designed to determine the response rates, survival and toxicities of single-agent gemcitabine (GEMZAR) and a combination of cisplatin/etoposide in chemonaive patients with non-resectable, locally advanced or metastatic non-small cell lung cancer (NSCLC). Gemcitabine 1000 mg/m2 was given as a 30-min intravenous infusion on days 1, 8, 15 of a 28-day cycle, cisplatin 100 mg/m2 on day 1, and etoposide 100 mg/m2 on days 1 (following cisplatin), 2 and 3. Major eligibility criteria included histologically confirmed non-small cell lung cancer, measurable disease, Zubrod performance status 0-2, no prior chemotherapy, no prior radiation of the measured lesion, and no CNS metastases. One hundred and forty-seven patients were enrolled, 72 in the gemcitabine and 75 in the cisplatin/etoposide arm. Patient characteristics were well-matched across both arms. Sixty-seven gemcitabine and 72 cisplatin/etoposide patients were qualified for efficacy analysis. There were no complete responses, but 12 partial responses in the gemcitabine arm and 11 in the cisplatin/etoposide arm, for protocol-qualified response but 12 partial responses in the gemcitabine arm and 11 in the cisplatin/etoposide arm, for protocol-qualified response rates of 17.9% (95%, CI: 9.6-29.2%,) and 15.3% (95% CI: 7.9-25.7%,), respectively. Median survival times were 6.6 months (95% CI: 4.9-7.3 months) for gemcitabine and 7.6 months (95% CI: 5.4-9.3 months) for cisplatin/etoposide. The 1-year survival probability estimate was 26% for gemcitabine and 24% for cisplatin/etoposide. There were no statistically significant between-group differences in time-to-event measures, but patients in the gemcitabine arm had a greater probability of achieving a tumour response after 2 months (probability estimate: 8 vs. 0%,) and of the response lasting at least 6 months (73 vs. 45%,). Clinical and haematologic toxicity was more pronounced in the cisplatin/etoposide arm. Quality-of-life measures indicated a significant worsening of symptomatology in the cisplatin/etoposide arm for hair loss, nausea and vomiting, and appetite loss. This randomized study provides further evidence that single-agent gemcitabine is an active and effective therapy for patients with non-resectable. locally advanced or metastatic NSCLC and good performance status, and that it is better tolerated than the combination cisplatin/ etoposide.     

Cisplatin and gemcitabine first-line chemotherapy followed by maintenance gemcitabine or best supportive care in advanced non-small cell lung cancer: a phase III trial

PURPOSE: The primary objective of this randomized phase III study was to show significant difference in median time to progression (TTP) in patients with advanced NSCLC treated with single-agent gemcitabine maintenance therapy versus best supportive care following gemcitabine plus cisplatin initial first-line therapy. PATIENTS AND METHODS: Chemonaive patients with stage IIIB/IV NSCLC received gemcitabine 1,250 mg/m(2) (days 1 and 8) plus cisplatin 80 mg/m(2) (day 1) every 21 days. Patients achieving objective response or disease stabilization following initial gemcitabine plus cisplatin therapy were randomized (2:1 fashion) to receive maintenance gemcitabine (1,250 mg/m(2) on days 1 and 8 every 21 days) plus best supportive care (GEM arm), or best supportive care only (BSC arm). RESULTS: Between November 1999 and November 2002, we enrolled 352 patients (median age: 57 years; stage IV disease: 74%; Karnofsky performance status (KPS) >80: 41%). Following initial therapy, 206 patients were randomized and treated with gemcitabine (138) or best supportive care (68). TTP throughout the study period was 6.6 and 5 months for GEM and BSC arms, respectively, while values for the maintenance period were 3.6 and 2.0 months (for p < 0.001 for both). Median overall survival (OS) throughout study was 13.0 months for GEM and 11.0 months for BSC arms (p = 0.195). The toxicity profile was mild, with neutropenia being most common grade 3/4 toxicities. CONCLUSION: Maintenance therapy with gemcitabine, following initial therapy with gemcitabine plus cisplatin, was feasible, and produced significantly longer TTP compared to best supportive care alone. Further studies are warranted to establish the place of maintenance chemotherapy in patients with advanced NSCLC.     

紫杉醇脂质体联合顺铂对比吉西他滨联合顺铂一线治疗伴有区域淋巴结转移的晚期非小细胞肺癌的临床研究

背景与目的：区域淋巴结转移与非小细胞肺癌(non-small cell lung cancer,NSCLC)患者预后显著相关,本研究旨在比较紫杉醇脂质体联合顺铂(liposomal paclitaxel plus cisplatin,LP)与吉西他滨联合顺铂(gemcitabine plus cisplatin,GP)一线治疗伴有区域淋巴结转移的NSCLC的近期疗效、远期生存及不良反应。方法：共随机入组55例患者(LP组和GP组分别为29例和26例),分别采用注射用紫杉醇脂质体(175 mg/m2)联合顺铂(75 mg/m2)和注射用吉西他滨(1 000 mg/m2)联合顺铂(75 mg/m²)进行治疗,21 d为1个周期。结果：对于肺癌原发灶,LP和GP组客观缓解率分别为37.9%和30.8%,疾病控制率分别为93.1%和80.8%,差异无统计学意义(P>0.05);对于区域转移的淋巴结,LP和GP组的客观缓解率分别为44.8%和15.4%,差异有统计学意义(P=0.022);LP组疾病控制率(93.1%)高于GP组(73.1%),差异无统计学意义(P=0.101)。LP和GP组的中位生存期分别为17.0个月和12.0个月,差异有统计学意义(P<0.05),两组患者1年生存率分别为86.2%(25/29)和57.7%(15/26),差异有统计学意义(P=0.039)。LP组血小板减少、胃肠道反应发生率明显低于GP组(P<0.05),而贫血、粒细胞减少、肝肾功能损伤、过敏反应等发生率两组差异无统计学意义(P>0.05)。结论：对于伴有区域淋巴结转移的NSCLC患者,LP方案可能更能使患者获益,不良反应更轻,耐受性好,值得进一步研究和临床推广应用。     

健择联合顺铂治疗晚期非小细胞肺癌疗效观察

目的 :探讨健择 (gemcitabine ,gemzar,GEM)联合顺铂治疗晚期非小细胞肺癌 (NSCLC)的疗效。方法 :36例初治晚期NSCLC患者应用健择 1g m2 ,静脉滴入 ,d1、d8,顺铂 10 0mg m2 ,静脉滴入 ,d1,每 2 1d为 1个周期 ,2～ 3个周期后评价疗效和毒副作用。结果 :完全缓解 (CR) 1例 ,部分缓解 (PR) 14例 ,总缓解率 4 1 7% ,中位生存期 39周 ,1年生存率 4 4 4 %。主要不良反应为骨髓抑制和恶心、呕吐。结论 :健择联合顺铂是治疗晚期NSCLC疗效较好方案 ,毒性可耐受。     

Randomized,multicenter, phase II study of gemcitabine plus cisplatin versus gemcitabine plus carboplatin in patients with advanced non-small cell lung cancer

BACKGROUND: We conducted a phase II randomized study to assess the efficacy, with response as the primary endpoint, and the toxicity of gemcitabine/cisplatin (GP) and gemcitabine/carboplatin (GC) in patients with advanced non-small cell lung cancer (NSCLC). METHODS: Patients were randomized to GP (gemcitabine 1200 mg/m(2), days 1 and 8 plus cisplatin 80 mg/m(2) day 2) or GC (gemcitabine 1200 mg/m(2), days 1 and 8 plus carboplatin AUC=5 day 2). Cycles were repeated every 3 weeks. RESULTS: Sixty-two patients were randomized to GP and 58 to GC. A total of 533 cycles were delivered (264 GP, 269 GC), with a median of four cycles/patient. The objective response rate was 41.9% (95% C.I., 29.6-54.2%) for GP and 31.0% (95% C.I., 18.2-42.8%) for GC (P=0.29). No significant differences between arms were observed in median survival (10.4 months GP, 10.8 months GC) and median time to progression (5.4 months GP, 5.1 months GC). Both regimens were very well tolerated with no statistical differences between arms in grade 3/4 toxicities. When all toxicity grades were combined, emesis, neuropathy and renal toxicity occurred more frequently on the GP arm (P<0.005). CONCLUSIONS: GC arm did not provide a significant difference in response rate compared with GP arm, with better overall tolerability. Carboplatin could be a valid alternative to cisplatin in the palliative setting.     

Gemcitabine and cisplatin versus mitomycin, ifosfamide, and cisplatin in advanced non-small-cell lung cancer: A randomized phase III study of the Italian Lung Cancer Project.

PURPOSE: To compare gemcitabine and cisplatin (GC) with mitomycin, ifosfamide, and cisplatin (MIC) chemotherapy in patients with stage IIIB (limited to T4 for pleural effusion and N3 for supraclavicular lymph nodes) or stage IV non-small-cell lung cancer (NSCLC). The end points were the evaluation of quality of life (QoL), response rates, survival, and toxicity. PATIENTS AND METHODS: Three hundred seven patients were randomized to receive either gemcitabine 1,000 mg/m(2) on days 1, 8, and 15 plus cisplatin 100 mg/m(2) on day 2, every 28 days, or mitomycin 6 mg/m(2), ifosfamide 3,000 mg/m(2), and mesna on day 1 plus cisplatin 100 mg/m(2) on day 2, every 28 days. The whole-blood cell count was repeated on day 1 in both arms and weekly in the GC arm before each gemcitabine administration. RESULTS: No major differences in changes in QoL were observed between the two treatment arms. The objective response rate was 38% in the GC arm compared with 26% in the MIC arm (P =.029). The median survival time was 8.6 months in the GC arm and 9.6 months in the MIC arm (P =.877, log-rank test). Grade 3 and 4 thrombocytopenia was significantly worse in the GC arm (64% v 28%, P <.001), whereas grade 3 and 4 alopecia was reported more commonly in the MIC arm (39% v 12%, P <. 001). CONCLUSION: We report an increased response rate without changes in QoL and a similar overall survival, time to progression, and time to treatment failure for the GC when compared with the MIC regimen in the treatment of advanced NSCLC.     

Randomized phase 2 study of irinotecan plus cisplatin versus gemcitabine plus vinorelbine as first-line chemotherapy with second-line crossover in patients with advanced nonsmall cell lung cancer

BACKGROUND: The current study was performed to compare the nonplatinum-based combination of gemcitabine and vinorelbine (GV) with the combination of irinotecan and cisplatin (IP) as first-line chemotherapy with second-line crossover in patients with advanced nonsmall cell lung cancer (NSCLC). METHODS: Patients were randomly assigned to received either irinotecan at a dose of 65 mg/m(2) plus cisplatin at a dose of 30 mg/m(2) (Arm A) or gemcitabine at a dose of 900 mg/m(2) plus vinorelbine at a dose of 25 mg/m(2) (Arm B), each of which was administered on Days 1 and 8 every 3 weeks as the first-line therapy followed by crossover at the time of disease progression. RESULTS: A total of 146 patients were enrolled (75 patients in Arm A and 71 patients in Arm B); 138 patients were evaluable for tumor response and toxicity. During first-line therapy, IP was found to result in more grade 2+ nausea and vomiting (toxicity was graded according to the National Cancer Institute Common Toxicity Criteria [version 2.0]) (41% vs 12%; P = .0001) and alopecia (36% vs 10%; P = .0003). Pneumonitis was noted only with GV therapy (7% vs 0%; P = .058). During second-line therapy, IP was found to result in more grade 3 diarrhea (17% vs 2%; P = .039) and GV featured more cases of grade 3+ neutropenia (78% vs 40%; P = .0003). IP tended to generate more tumor responses (38% vs 26% as first-line therapy, and 30% vs 13% as second-line therapy) compared with GV. IP also demonstrated a favorable trend in median progression-free survival (4.6 months vs 3.8 months as first-line therapy and 4.5 months vs 2.6 months as second-line therapy) and overall survival (15.9 months vs 13.1 months; P = .3), but this difference was not statistically significant. The majority of patients who were refractory to IP also failed to respond to GV in the second-line setting. CONCLUSIONS: The platinum-based IP regimen appeared to be superior to the GV combination in terms of response rate. However, given the similar survival and better tolerability of the nonplatinum GV regimen, either treatment sequence would appear to be acceptable for the treatment of patients with advanced NSCLC.     

Intra-patient alternated dose escalation of paclitaxel and gemcitabine versus paclitaxel followed by fixed dose rate infusion of gemcitabine in fit elderly non-small cell lung cancer patients. A Southern Italy Cooperative Oncology Group randomised phase II trial

PURPOSE: This study was undertaken to select the best schedule of administration for the paclitaxel plus gemcitabine combination in fit elderly patients affected by locally advanced or metastatic non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Ninety-eight patients in stage III or IV NSCLC, aged 70 years or more and in ECOG performance status (PS)相似文献   

Prolonged gemcitabine infusion in advanced non-small-cell lung cancer with stable disease after gemcitabine 30-min infusion

BACKGROUND: Although 30-min gemcitabine infusion has become the standard administration, pre-clinical and clinical studies have suggested the possibility that an infusion rate of 10 mg/m(2) per minute may be more effective. The main objective of this study was to investigate whether the pursuance of gemcitabine, administered at a prolonged infusion rate, was able to convert stable disease to objective response after two or three cycle of standard administration. The secondary end-point was the evaluation of the new schedule toxicity. PATIENTS AND METHODS: Thirty-eight patients, with stage IIIA-B and IV NSCLC already treated by two or three cycles of 30-min gemcitabine infusion, alone or in combination with cisplatin, were enrolled: 26 patients (aged <70 years) were treated with cisplatin 80 mg/m(2) on day 1 plus gemcitabine 1200 mg/m(2) over 120 min on day 1 and 8 every three weeks and 12 patients (aged > or =70 years) were treated with gemcitabine alone 1200 mg/m(2) over 120 min on day 1 and 8 every three weeks, for two courses. Simon's two stage minimax design was applied to calculate the sample size. Assuming p(0) (low conversion rate) 5%, p(1) (target conversion rate of interest) 20%, alpha error 0.05, beta error 0.10 a total of 29 evaluable patients had to be accrued during stage 1. In case at least one objective response was observed, a further nine evaluable patients had to be enrolled into the study during stage 2. The regimen was considered promising if > or =4 objective responses out of 38 evaluable patients were observed. RESULTS: Thirty-eight patients were evaluable for response and in five patients (with stable disease after two courses of gemcitabine 30' infusion) a partial response was observed (conversion rate 13.1%, 95% confidence interval 4.4-28%). Toxicities were more frequently observed with cisplatin plus 120-min gemcitabine infusion: grade 3-4 neutropenia, thrombocytopenia and anaemia in 28, 22 and 16% of the courses, respectively. CONCLUSIONS: The prolongation of gemcitabine infusion time is able to convert stable disease to partial response in 13% of the cases. The haematological toxicity seems enhanced with cisplatin plus gemcitabine prolonged infusion.     

Phase II trial of low-dose gemcitabine in prolonged infusion and cisplatin for advanced non-small cell lung cancer

PURPOSE: To evaluate the efficacy and safety of the combination of gemcitabine at a low dose of 250 mg/m(2) in 6h prolonged infusion with cisplatin in chemonaive patients with advanced non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Fifty-eight chemonaive patients with stage IIIB or IV NSCLC were included, 39 males and 19 females, with a median age 61 years (range 28-73). Thirty-four (58.6%) patients had adenocarcinoma, 18 (31.0%) squamous cell, and 6 (10.4%) others. Seventeen (29.3%) had stage IIIB and 41 (70.7%) stage IV. Treatment consisted of 250 mg/m(2) gemcitabine in a 6h infusion on days 1 and 8, and cisplatin at 75 mg/m(2) on day 2 of a 3-week cycle. A total of 219 chemotherapy cycles were administered, with a median of 4 cycles per patient (range 1-6). RESULTS: Of the 58 patients enrolled, all were evaluated for toxicity and 56 assessed for response. The overall response rate was 39.3% (95% confidence interval, 26.5-52.1%) with complete and partial responses of 3.6 and 35.7%, respectively. The median time to disease progression was 5.5 months (95% CI, 4.3-6.7 months), and median overall survival time was 10.5 months (95% CI, 8.5-12.5 months). One-year survival rate was 41.4%. Hematologic toxicity was fairly mild, and grades 3-4 hematologic toxicities consisted of neutropenia in 18.9% of patients, thrombocytopenia in 10.3%, and anemia in 6.9%. No patients required platelet transfusions, no bleeding episodes were recorded, and three patients received packed red blood cells (RBC) transfusions. The main nonhematologic toxicities included grade 3 nausea/vomiting in 27.6% of patients, grade 1-2 alopecia in 63.8%, and grade 1-2 skin rash in 17.3 %. CONCLUSIONS: Low-dose gemcitabine in 6h prolonged infusion plus cisplatin is effective in NSCLC treatment. Toxicity, especially myelosuppression, is remarkably mild.     

Randomized phase II comparison of dose-intense gemcitabine: thirty-minute infusion and fixed dose rate infusion in patients with pancreatic adenocarcinoma.

PURPOSE: To conduct a randomized phase II trial of dose-intense gemcitabine using a standard 30-minute infusion or the fixed dose rate (FDR) infusion (10 mg/m2/min) in patients with pancreatic adenocarcinoma. PATIENTS AND METHODS: In this prospective trial, patients with locally advanced and metastatic pancreatic adenocarcinoma were treated with 2,200 mg/m2 gemcitabine over 30 minutes (standard arm) or 1,500 mg/m2 gemcitabine over 150 minutes (FDR arm) on days 1, 8, and 15 of every 4-week cycle. The primary end point of this trial was time to treatment failure. Secondary end points included time to progression, median survival, safety, and pharmacokinetic studies of gemcitabine. RESULTS: Ninety-two patients were enrolled onto this study; 91% of the patients had metastatic disease. Time to treatment failure was comparable in both treatment groups; however, the median survival for all patients was 5.0 months in the standard arm and 8.0 months in the FDR arm (P =.013). For patients with metastases, the median survival was 4.9 months in the standard arm and 7.3 months in FDR arm (P =.094). The 1- and 2-year survival rates for all patients were 9% (standard arm) versus 28.8% (FDR; P =.014) and 2.2% (standard arm) versus 18.3% (FDR; P =.007), respectively. Patients in the FDR infusion arm experienced consistently more hematologic toxicity. Pharmacokinetic analyses demonstrated a two-fold increase in intracellular gemcitabine triphosphate concentration in the FDR arm (P =.046). CONCLUSION: Pharmacokinetic and clinical data in this trial supports the continued evaluation of the FDR infusion strategy with gemcitabine.