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

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

Single-agent gemcitabine in pretreated patients with non-small-cell lung cancer: results of an Argentinean multicentre phase II trial.

The activity and mild toxicity profile of single-agent gemcitabine therapy in untreated (chemonaive) patients with non-small-cell lung cancer (NSCLC) is well documented. This phase II trial was conducted to determine the objective tumour response rate and toxicity profile of single-agent gemcitabine in pretreated patients with NSCLC. Patients with histological evidence of advanced NCSLC stage IIIB or IV; at least one prior chemotherapy regimen including a platinum or taxane analogue; an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2; clinically measurable disease; adequate bone marrow reserve; and adequate renal function; received 1000 mg m(-2) gemcitabine administered over 30 min on days 1, 8 and 15 of a 28-day cycle defined as 3 weekly treatments followed by 1 week of rest. Twenty-nine patients were evaluated for efficacy and 32 for toxicity. One patient achieved a complete response and five patients had a partial response resulting in a total response rate of 20.6% (95% confidence interval (CI) 6-34). Median response duration was 7 months (range 4-11 months). Twelve (41%) patients reached stable disease after two cycles of therapy and 11 (38%) patients had disease progression. Median progression-free survival time was 3 months and median overall survival time was 5.5 months. Toxicity was generally mild (grades 0-2). Severe (grade 3 or 4) haematological toxicities included grade 3 anaemia in one patient and grade 3 thrombocytopenia in two patients. Severe non-haematological toxicities included one patient each with grade 3 liver transaminase elevations, nausea/vomiting and diarrhoea. This study confirms the activity and safety of single-agent gemcitabine in pretreated patients with advanced NSCLC who are refractory or sensitive to first-line therapy.     

Phase I study of the combination of gemcitabine and nedaplatin for treatment of previously untreated advanced non-small cell lung cancer

This trial was conducted to determine the maximum-tolerated dose (MTD), principal toxicity, and recommend dose for phase II study of the combination of gemcitabine and nedaplatin in patients with advanced non-small cell lung cancer (NSCLC). Patients with previously untreated NSCLC were eligible if they had a performance status of 0-2, were 75 years or younger, and had adequate organ function. The doses of gemcitabine (days 1, 8) and nedaplatin (day 1) studied were 800/60, 800/70, 800/80, 1000/80, and 1000/100 (mg/m(2)), repeated every 3 weeks. Toxicity could be assessed in all 21 patients enrolled, response could be assessed in 20 patients. The patients were 12 men and 9 women with a mean age of 69 years (range, 47-75 years). Four patients had stage IIIB disease and 17 patients had stage IV disease. The most common histologic type was adenocarcinoma. The MTD was not reached even at the highest doses. The most frequent toxic effects were thrombocytopenia and neutropenia: grade 3 or 4 thrombocytopenia was observed in 19% of patients, and grade 3 or 4 neutropenia in 24% of patients. Nonhematologic toxicities were mild. Grade 3 hepatic dysfunction occurred in 3 patients. Relatively few patients required dose modifications. The median dose-intensities were 91.5 and 93.1%, respectively, of the planned doses of gemcitabine and nedaplatin. The overall response rate was 35% (95% confidence interval, 15.4-59.2%). All responses were seen above level 3. The MTD was not reached even at the highest combination doses. We recommend doses of 1000 mg/m(2) of gemcitabine and 100 mg/m(2) of nedaplatin for phase II study. This combination chemotherapy is active and well tolerated and warrants phase II study.     

Phase II trial of paclitaxel plus gemcitabine in patients with locally advanced or metastatic non-small-cell lung cancer.

PURPOSE: Given the cisplatin-related myelotoxicity and nonhematologic toxicities, we were prompted to undertake a study of the noncisplatin combination of paclitaxel plus gemcitabine to evaluate the efficacy, tolerance, and survival of this combination in patients with locally advanced and metastatic non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients received gemcitabine 2,000 mg/m(2) and paclitaxel 150 mg/m(2) on days 1 and 15 of a 28-day cycle, for a maximum of eight cycles. RESULTS: Between December 1997 and June 1998, 89 untreated NSCLC patients were enrolled; 30 (34%) had stage IIIB disease (23 with malignant pleural effusion and seven without), and 59 (66%) had stage IV disease. Eighty-six percent of patients had a performance status of 0 or 1. The median number of cycles administered was four (range, one to eight cycles). The mean dose-intensity for both paclitaxel and gemcitabine was nearly 100%. Hematologic and nonhematologic toxicities were mild. Thirty-eight patients received second-line chemotherapy after completion of the study. The overall intent-to-treat response rate was 32.2%, with a higher response rate for stage IIIB patients (43.3%) than for stage IV patients (26.3%). Overall median survival was 9.9 months, and 1-year survival was 38.8% (14.2 months for stage IIIB and 7.7 months for stage IV; P =.007). Median survival was 10.2 months for patients with a performance status of 0 or 1 and 4.8 months for patients with a performance status of 2 (P =.007). CONCLUSION: A biweekly paclitaxel/gemcitabine regimen was well tolerated, with an acceptable response rate and a reasonable median survival time, especially in patients with good performance status. It merits further exploration in future studies.     

Phase I study of the combination of nedaplatin and gemcitabine in previously untreated advanced squamous cell lung cancer

Purpose

The objectives of this phase I trial were to evaluate the toxicity of the nedaplatin/gemcitabine regimen, determine the maximum tolerated doses (MTDs) of these agents, and observe the anti-tumor effects of this regimen on advanced squamous cell lung cancer.

Methods

Patients with previously untreated advanced squamous cell lung cancer were eligible if they had a performance status of 0 or 1 with adequate organ function. The doses of gemcitabine (days 1 and 8) and nedaplatin (day 8) studied were 800/70, 1,000/80, 1,000/90, and 1,000/100 (mg/m²), repeated every 3?weeks.

Results

Toxicity and response could be assessed in all 13 patients enrolled. The patients included 12 men and one woman with a median age of 69?years (range 57?C81?years). Three patients had stage IIIB disease and 10 patients had stage IV disease. The MTDs were reached at 1,000?mg/m² gemcitabine and 80?mg/m² nedaplatin. The most frequent toxic effects were thrombocytopenia and neutropenia; grade 3 or 4 thrombocytopenia was observed in 23% of patients, and grade 3 or 4 neutropenia was seen in 46% of patients. Non-hematologic toxicities were mild. Grade 3 fatigue, nausea/vomiting, and appetite loss occurred in two patients. The overall response rate was 62%.

Conclusions

We recommend doses of 800?mg/m² gemcitabine and 70?mg/m² nedaplatin for phase II study. This combination chemotherapeutic regimen is active and well tolerated.     

Phase I-II study of gemcitabine and carboplatin in stage IIIB-IV non-small-cell lung cancer.

PURPOSE: Platinum-based chemotherapy currently represents standard treatment for advanced non-small-cell lung cancer. Gemcitabine is one of the most interesting agents currently in use in advanced non-small-cell lung cancer, and high response rates have been reported when it is administered in combination with cisplatin. The aim of the present study was to evaluate the combination of gemcitabine and carboplatin in a phase I-II study. PATIENTS AND METHODS: Chemotherapy-naive patients with stage IIIB-IV non-small-cell lung cancer received carboplatin at area under the concentration-time curve (AUC) 5 mg/mL/min and gemcitabine at an initial dose of 800 mg/m2, subsequently escalated by 100 mg/m2 per step. Gemcitabine was administered on days 1 and 8 and carboplatin on day 8 of the 28-day cycle. Dose escalation proceeded up to dose-limiting toxicity (DLT), which was defined as grade 4 neutropenia or thrombocytopenia or grade 3 nonhematologic toxicity. RESULTS: Neutropenia was DLT, inasmuch as it occurred in three of five patients receiving gemcitabine 1,200 mg/m2. Nonhematologic toxicities were mild. Gemcitabine 1,100 mg/m2 plus carboplatin AUC 5 was recommended for phase II studies. An objective response was observed in 13 (50%) of 26 patients, including four complete responses (15%) and nine partial responses (35%). Median duration of response was 13 months (range, 3 to 23 months). Median overall survival was 16 months (range, 3 to 26 months). CONCLUSION: The combination of gemcitabine and carboplatin is well tolerated and active. Neutropenia was DLT. The observed activity matches that observable in cisplatin-gemcitabine studies, whereas duration of response and survival are even higher. A phase II trial is under way.     

A phase II trial of combination of CPT-11 and cisplatin for advanced non-small-cell lung cancer. CPT-11 Lung Cancer Study Group.

A phase I trial of the combination of irinotecan (CPT-11) with cisplatin in advanced non-small cell lung cancer (NSCLC) showed a very promising response rate of 54% in previously untreated NSCLC patients. This study was conducted to confirm the activity and toxicities of CPT-11 and cisplatin combination for previously untreated NSCLC in a multi-institutional phase II study. Seventy patients with stage IIIB or IV NSCLC received CPT-11 60 mg m(-2) intravenously (i.v.) on days 1, 8 and 15, and cisplatin 80 mg m(-2) (i.v.) on day 1 every 4 weeks. Assessments were made of response, survival and toxicities. Sixty-nine were eligible, and evaluable for toxicities and survival, and 64 patients evaluable for response. Thirty-three patients (52%; 95% confidence interval 39-64%) achieved an objective response, with one complete response (2%) and 32 partial responses (50%). The median duration of response was 19 weeks and the overall median survival time was 44 weeks. The 1-year survival rate was 33%. The major toxic effects were leucopenia and diarrhoea. Grade 3 or 4 leucopenia, neutropenia, and diarrhoea occurred in 32 patients (46%), 53 patients (80%), and 13 patients (19%) respectively. A combination of CPT-11 and cisplatin is very effective against non-small-cell lung cancer with acceptable toxicities.     

UFT plus gemcitabine combination chemotherapy in patients with advanced non-small-cell lung cancer: a multi-institutional phase II trial

A multi-institutional phase II trial was conducted to evaluate the efficacy and toxicity of combination chemotherapy consisting of gemcitabine and UFT, which is composed of tegafur and uracil, for non-small-cell lung cancer (NSCLC) patients. Patients with advanced NSCLC received an oral administration of UFT (tegafur 200 mg m(-2)) b.i.d. from days 1 to 14 and intravenous injection of gemcitabine 900 mg m(-2) on days 8 and 15. This treatment was repeated every 4 weeks. A total of 44 patients were enrolled into this trial. The median age of all patients was 74 years, with 23 patients younger than 75 years and 21 patients with 75 years of age or older. A total of 18 patients (41%) achieved a partial response. The median survival time was 13.2 months and the 1-year survival rate was 59%. The most common grade 3-4 toxicity was neutropenia (57%). The frequency of grade 3 nonhaematologic toxicities was less than 5%. In addition, no significant difference in the response, survival or toxicities was observed between the patients younger than and those older than 75 years of age. This combination chemotherapy demonstrated a promising effectiveness and acceptable toxicity in patients with advanced NSCLC, even in patients older than 75 years. .     

A phase II study of cisplatin, vindesine and continuously infused 5-fluorouracil in the treatment of advanced non-small-cell lung cancer. Osaka Lung Cancer Chemotherapy Study Group.

Fifty-two previously untreated patients with advanced non-small-cell lung cancer (NSCLC) were treated on a 14 day cycle with cisplatin (60 mg m-2 i.v.) and vindesine (3 mg m-2 i.v.) on day 1, followed by a 3 day continuous infusion of 5-fluorouracil (800 mg m-2 day-1) starting on day 8. An overall response rate of 40.4% was observed in 47 evaluable patients, which included one complete response and 18 partial responses. Responses were achieved in 61.1% of stage 3 patients and 27.6% of stage 4 patients. The median progression-free interval was 19.3 weeks, and median survival time was 41.6 weeks (47.1 weeks for patients with stage 3 disease and 38.7 weeks for those with stage 4 disease). Toxicity was well tolerated. Gastrointestinal and renal toxicities did not exceed WHO grade 2. Grade 3 or 4 leucopenia and anaemia occurred in nine (19%) and four (9%) patients respectively, but only grade 2 thrombocytopenia was observed. Phlebitis at the infusion site was observed in 24 patients (53%). This treatment programme achieved a response rate similar to other active combination regimens for the treatment of advanced NSCLC, and was less toxic.     

Phase II Trial of Dose-dense Pemetrexed,Gemcitabine, and Bevacizumab in Patients With Advanced,Non–Small-cell Lung Cancer

Introduction

Platinum-based chemotherapy is standard for untreated, advanced non-small-cell lung cancer (NSCLC). We investigated the activity and tolerability of the novel combination of dose-dense pemetrexed, gemcitabine, and bevacizumab in patients with advanced NSCLC.

吉西他滨联合顺铂治疗30例非小细胞肺癌

目的:评价吉西他滨联合顺铂治疗非小细胞肺癌的疗效及毒副作用。方法:30例晚期非小细胞肺癌,初治14例,复治16例,采用吉西他滨1000mg/m2,第1、8天静脉滴注。顺铂:80mg/m2,分3天静脉滴注,21天为1个周期,至少连用2个周期。结果:部分缓解(PR)14例,无变化(NC)13例,病变进展(PD)3例,有效率为46.67%。主要毒副反应为骨髓抑止、恶心和呕吐等。结论:吉西他滨联合顺铂对治疗非小细胞肺癌有较好的临床疗效,毒副反应轻,易耐受。     

吉西他滨联合顺铂治疗晚期非小细胞肺癌临床研究

目的：观察吉西他滨联合顺铂治疗晚期非小细胞肺癌的疗效及毒副反应。方法：经病理组织学或细胞学证实的43例晚期非小细胞肺癌患者给予吉西他滨1000mg/m2静滴,第1,8,15天,顺铂30mg/m2静滴,第1－3天,28天为一周期,或吉西他滨1200mg/m2静滴,第1,8天,顺铂30mg/m2静滴,第1－3天,21天为一周期,结果：全组CR1例,PR20例,SD13例,PD9例,总有效率48．8％,初治病例有效率为62．5％,复治病例为31．6％,两组间差异具有显著性（P＜0．05）,毒副反应以白细胞及血小板下降为常见,但均可耐受,结论：吉西他滨联合顺铂治疗晚期非小细胞肺癌具有较好的疗效。毒性可以耐受。     

Phase II study of gemcitabine and carboplatin in patients with advanced non-small-cell lung cancer

Purpose To evaluate the efficacy and safety of gemcitabine in combination with carboplatin at standard rate or fixed dose rate infusion in patients with advanced non-small-cell lung cancer (NSCLC). Patients and methods In this prospective study, patients with chemonaive advanced NSCLC were randomized to receive gemcitabine at a standard rate (gemcitabine 1,200 mg/m² over 30 min, the standard arm) or a fixed dose rate (gemcitabine 1,200 mg/m² over 120 min, the FDR arm) on days 1 and 8 every 3 week cycle. In both treatment arms, carboplatin at AUC of 5 was administered over 4 h following gemcitabine on day 1 of each cycle. Results From November 2003 to June 2005, a total of 42 patients, in which 7 (17%) patients had stage III_B disease and 35 (83%) had stage IV disease, were enrolled into this study. All patients were included in efficacy and toxicity assessment. No patient had a complete response. Seven (33%) patients in the standard arm and 10 (48%) in the FDR arm had a partial response. The median time to progression and median overall survival time in the standard arm was 5.4 months (95% CI, 3.8–7 months) and 11.5 months (95% CI, 8.2–14.8 months), respectively, while in the FDR arm was 6.5 (95% CI, 4.4–8.6 months) months, 12.0 months (95% CI, 11.3–12.7 months), respectively. The most frequently reported grade 3 or 4 hematological toxicities were thrombocytopenia (38% patients in the standard arm and 43% in the FDR arm) and neutropenia (24% in the standard arm and 33% in the FDR arm). Although hematological toxicity occurred in a little higher percent of patients in the FDR arm than in the standard arm, there were no discernible differences by statistical analysis in both treatment arms (P > 0.05). And significant nonhematologic toxicities were infrequent and tolerable in both arms. No significant difference existed also (P > 0.05). Conclusion In this phase II study, gemcitabine in combination with carboplatin either at standard rate or fixed dose rate infusion was clinically effective and well tolerated in patients with advanced NSCLC.     

吉西他滨联合顺铂治疗Ⅲ、Ⅳ期非小细胞肺癌的临床评价

 目的 观察吉西他滨（GEM）联合顺铂（DDP）治疗Ⅲ、Ⅳ期非小细胞肺癌（NSCLC）的疗效及毒副反应。方法 2000年2月至2005年6月，对79例NSCLC患者采用GP方案化疗，用法：GEM 1000 mg／m2第1、8天给药；DDP 90 mg／m2分3 d，21 ~ 28 d为1周期，2 ~ 3周期评价疗效。结果 79例分别完成2～5周期联合化疗，其中完全缓解（CR）0例，部分缓解（PR）为25 %（20／79），稳定（SD）为27 %（21／79），临床受益反应（CBR）为52 %（41／79）。初治的39例中，CBR为56.4 %（22／39）；复治40例中， CBR为47.5 %（19／40）。毒副反应主要为血液学毒性，以血小板减少或白细胞数降低较为明显。结论 GEM联合DDP治疗Ⅲ、Ⅳ期NSCLC，具有良好的疗效及耐受性。     

吉西他滨联合奈达铂与紫杉醇治疗顺铂耐药的转移性鼻咽癌

 目的　观察吉西他滨联合奈达铂与紫杉醇治疗对顺铂耐药的转移性鼻咽癌的近期疗效及不良反应。 方法　15例顺铂方案化疗失败的转移性鼻咽癌患者。吉西他滨1000 mg／m2,第1、8天;奈达铂70 mg／m2,第1天;紫杉醇135 mg／m2,第1天;21 d为1个疗程,疗效评价采用RECIST 3.0标准。结果　全组15例患者CR 1例 ,PR 5例 ,SD 6例 ,PD 3例 ,总有效（CR+PR）率40.0 %。中位TTP为4.7个月,中位生存期为6.3个月。主要不良反应为血液学毒性,Ⅲ＋Ⅳ度骨髓抑制的发生率分别为：白细胞减少40.0 %、贫血6.7 %、血小板减少20.0 %。其他不良反应轻微。结论　吉西他滨联合奈达铂与紫杉醇的化疗方案可作为顺铂耐药转移性鼻咽癌的二线方案。     

Gemcitabine, vinorelbine and cisplatin combination chemotherapy in advanced non-small cell lung cancer: a phase II trial

The purpose of this phase II trial was to investigate the efficacy and safety of a combination chemotherapy with gemcitabine, vinorelbine and cisplatin in the first-line treatment of advanced non-small cell lung cancer (NSCLC). Patients with NSCLC stage IIIB or IV disease received 1000 mg/m(2) gemcitabine and 25 mg/m(2) vinorelbine on days 1 and 8 and 75 mg/m(2) cisplatin on day 2, every 3 weeks. From December 1998 to May 1999, 31 patients (21 stage IV and 10 stage IIIB disease), with a median age of 59 years (range 40-72 years) were enrolled. The overall intent-to-treat response rate was 45% (95% confidence interval (CI): 27-64%) with 2 complete responders (CR) and 12 partial responders (PR), 7 patients had stable disease and 10 progressed. Median survival was 12.8 months (95% CI: 6.5-12.8+ months), median time to progression was 5.1 months (95% CI: 3.5-7.7 months), and the 1-year survival rate was 52.9% (95% CI: 36.7-76.2%). Patients with stage IIIB disease had a significantly longer overall survival than patients with stage IV disease (P=0.05). Transient World Health Organization (WHO) grade IV leucopenia, anaemia and thrombocytopenia occurred in 3 (10%), 2 (6%) and 3 (10%) patients, respectively. The predominant non-haematological toxicities were alopecia and nausea/vomiting. 15 patients (48%) had WHO grade II and III alopecia and 14 patients (45%) nausea/vomiting. The combination of gemcitabine, vinorelbine and cisplatin has demonstrated major antitumour efficacy in advanced NSCLC with a manageable toxicity profile.     

A Pooled Study on Combination of Gemcitabine and Nedaplatin for Treating Patients with Non-small Cell Lung Cancer

Background: This analysis was conducted to evaluate the efficacy and safety of a combination of gemcitabineand nedaplatin in treating patients with non-small cell lung cancer. Methods: Clinical studies evaluating theefficacy and safety of a combination of gemcitabine and nedaplatin with attention to response and safety forpatients with non-small cell lung cancer were identified using a predefined search strategy. Pooled responserates for gemcitabine and nedaplatin were calculated. Results: In gemcitabine and nedaplatin based regimens, 4clinical studies including 112 patients with non-small cell lung cancer were considered eligible for inclusion. Thepooled analysis suggested that the pooled reponse rate was 40.2% (45/112). Main side effects included grade 3-4neutropenia, thrombocytopenia, and anemia. Grade 3-4 nonhematological toxicity included nausea and vomiting,diarrhea, and hepatic dysfunction. There were no treatment-related deaths. Conclusion: This evidence basedanalysis suggests that the combination of gemcitabine and nedaplatin is associated with good response rate andaccepted toxicity for treating patients with non-small cell lung cancer.     

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

PURPOSE: 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. PATIENTS AND METHODS: 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. RESULT: 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. CONCLUSION: The combination of gemcitabine, cisplatin and UFT is an active and well-tolerated first-line regimen in patients with advanced NSCLC.     

Combination of low-dose cisplatin and gemcitabine for treatment of elderly patients with advanced non-small-cell lung cancer

PURPOSE: To evaluate the feasibility, toxicity and efficacy of the combination of low-dose cisplatin (CDDP) and gemcitabine (GEM) in elderly patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: This phase II trial included 46 patients aged 70 years or older with previously untreated advanced NSCLC. All patients were evaluable for response and toxicity. Treatment consisted of CDDP 50 mg/m(2) on day 1 plus GEM 1000 mg/m(2) on days 1 and 8. The regimen was repeated every 21 days. Patients received a minimum of three courses unless progressive disease was detected. RESULTS: A total of 190 GEM-CDDP courses were administered (median 4.1 courses per patient). The chemotherapy regimen was well tolerated. No patients developed grade 4 toxicity. Grade 3 toxicities were as follows: neutropenia in six patients (13%), and anemia, thrombopenia and nausea/vomiting in one (2%) each. Two patients (4%) had mild nephrotoxicity. Of the 46 patients, 16 had a partial response (35%, 95% confidence interval, CI, 28-52%), 17 (37%) remained stable and 13 (28%) had disease progression. Eastern Cooperative Oncology Group performance status improved in 17 patients (37%), whereas 25 (54%, 95% CI 44-74%) showed a clinical benefit. Median time to progression was 20 weeks. Overall median survival was 44 weeks, with a 1-year actuarial survival rate of 35%. CONCLUSIONS: The combination of low-dose CDDP and GEM for elderly patients with advanced NSCLC is an effective and well-tolerated chemotherapeutic approach.     

Dose-escalation study of weekly irinotecan and daily carboplatin with concurrent thoracic radiotherapy for unresectable stage III non-small cell lung cancer

Dose-escalation study was performed to evaluate the maximum tolerated dose, recommended dose and toxicity profile of weekly irinotecan with daily carboplatin and concurrent thoracic radiotherapy in patients with locally advanced non-small-cell lung cancer. Thirty-one previously untreated patients with unresectable stage III non-small-cell lung cancer were enrolled in this study. Patients received weekly irinotecan plus carboplatin (20 mg x m(-2) daily for 5 days a week) for 4 weeks and thoracic radiotherapy (60 Gy in 30 fractions). The irinotecan dose was escalated from 30 mg x m(-2) in increments of 10 mg x m(-2). Four irinotecan dose levels were given and 30 patients were assessable. Their median age was 62 years (range: 52-72 years), 28 had a performance status of 0-1 and two had a performance status of 2, 12 had stage IIIA disease and 18 had IIIB disease. There were 19 squamous cell carcinomas, 10 adenocarcinomas, and one large cell carcinoma. The dose-limiting toxicities were pneumonitis, esophagitis, thrombocytopenia and neutropenia. The maximum tolerated dose of irinotecan was 60 mg x m(-2), with two patients developing grade 4 pulmonary toxicity and one patient died of pneumonitis (grade 5). The recommended dose of irinotecan was 50 mg x m(-2). Other grade 3 or 4 toxicities were nausea and vomiting. Three patients achieved complete remission and 15 had partial remission, for an objective response rate of 60.0%. The median survival time was 14.9 months, and the 1- and 2-year survival rates were 51.6% and 34.2%, respectively. The study concluded that the major toxicity of this regimen was pneumonitis. This therapy may be active against unresectable non-small-cell lung cancer and a phase II study is warranted.