Elderly patients with advanced non-small cell lung cancer. A pase II study with weekly cisplatin and gemcitabine

OBJECTIVES: The incidence of non-small cell lung cancer (NSCLC) is increasing among the elderly. We studied the toxicity and efficacy of a weekly schedule of gemcitabine and cisplatin in elderly patients with advanced NSCLC. METHODS: Patients aged 70 years or above with advanced NSCLC were treated in a phase II prospective trial with gemcitabine 1,000 mg/m(2) and cisplatin 35 mg/m(2) on days 1, 8 and 15 every 28 days. RESULTS: Forty-eight patients with a median age of 74 years (range 70-78) participated in the study. We observed 14 cases with partial response, 14 with stable disease and 16 with progressive disease, whilst 4 patients were not evaluable. By intention-to-treat analysis, partial response rate was 31.8% whilst progressive disease was 33.3%. Median survival was 9 months; 1-year survival probability was 34.4% and median time to progression was 4 months. Grade III-IV leukopenia was observed in 5/48 patients (10.4%), 20/48 patients (41.7%) had grade III-IV thrombocytopenia and 7/48 patients (14.6%) had grade III-IV anemia. One patient experienced grade III emesis and 2 patients had grade III-IV fatigue. CONCLUSIONS: At this dose and schedule the combination of gemcitabine and cisplatin appears to be an active and well-tolerated regimen for elderly patients with advanced NSCLC.     

Phase II study with gemcitabine, ifosfamide and cisplatin in advanced non-small cell lung cancer

The aim of the present study was to determine the clinical activity and toxicity of a novel chemotherapy combination regimen of gemcitabine, ifosfamide and cisplatin (GIP), administered every 3 weeks, in patients with inoperable non-small cell lung cancer (NSCLC). From October 1998 to July 1999, 18 previously untreated stages IIIb (4) and IV (14) patients were enrolled into the study. Gemcitabine and ifosfamide (with mesna as uroprotection) was administered on days 1 and 6, at a dose of 1000 and 1500 mg/m², respectively; and cisplatin was given on day 1 at a dose of 60 mg/m², every 3 weeks. All 18 patients were evaluable for response and toxicity profiles. One patient achieved a complete response, and 11 patients achieved a partial response, with an overall response rate of 66.7% (95% CI, 45–89%). The main toxicity was hematological, a NCI grade 3–4 neutropenia in 16 patients (88.9%) during the treatment course. Febrile neutropenia occurred in three patients (16.6%). Grade 3 anemia occurred in eight patients (44.4%) and grade 3–4 thrombocytopenia occurred in 11 patients (61.1%). Non-hematological toxicity was mild and tolerable. No toxic death occurred. The median survival was 12.7 months and 1 year survival was 58.4%. The GIP combination chemotherapy produced a high response rate in advanced NSCLC; however, there was a relatively high percentage of hematological toxicity that still could be tolerated. A randomized trial comparing GIP to a two-drug combination of gemcitabine and cisplatin is planned.     

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.     

A multicenter phase II study of sequential vinorelbine and cisplatin followed by docetaxel and gemcitabine in patients with advanced non-small cell lung cancer

PURPOSE: To evaluate the activity and toxicity of the sequential administration of vinorelbine/cisplatin (VC regimen) followed by the docetaxel/gemcitabine (DG regimen) combination in patients with advanced non-small cell lung cancer (NSCLC). PATIENTS AND TREATMENT: Fifty-nine previously untreated patients with advanced/metastatic NSCLC received three cycles of cisplatin 80 mg/m(2) (day 1), and vinorelbine 30 mg/m(2) (days 1 and 8 every 3 weeks; VC regimen), followed by six cycles of docetaxel (65 mg/m(2), day 1) and gemcitabine (1,500 mg/m(2), day 1), (DG regimen) every 2 weeks. RESULTS: One (1.7%) complete and 26 (44.1%) partial responses were achieved for an overall response rate of 45.8% (95% CI 33.05-58.48%); 12 (20.3%) patients had stable disease and 20 (33.9%) progressive disease. The median time to progression was 5.3 months, the median survival time 12.5 months and the 1-year survival rate 51%. The main toxicity was grade III/IV neutropenia occurring in 25.5% of patients; all other hematologic and non-hematologic toxicities were relatively infrequent. CONCLUSIONS: The sequential administration of VC and DG regimens was well tolerated and active against advanced NSCLC and merits to be further evaluated against a single doublet.     

Phase II study of regimen of gemcitabine and cisplatin in advanced non-small cell lung cancer

BACKGROUND: Cisplatin-based chemotherapy is the standard treatment for advanced non-small cell lung cancer (NSCLC). Many novel drugs, including gemcitabine, navelbine, paclitaxel and docetaxel have been used in combination with cisplatin. Of these drugs, gemcitabine is reported to have a high response rate and acceptable toxicity. The aim of this study was to evaluate the efficacy and safety of the combination of gemcitabine and cisplatin. METHODS: Thirty-two patients with NSCLC, who met the selection criteria from June 1998 to January 1999, were enrolled. All of them were confirmed by histology and were in an advanced stage, i.e. stage IIIB with pleural effusion or stage IV. Cisplatin at a dose of 80 mg/m2 was given monthly on day 15, in combination with gemcitabine at a dose of 1000 mg/m2 administered on days 1, 8 and 15 of the 28-day cycle. RESULTS: Of the 32 assessable patients, two showed complete remission and 11 achieved partial remission. The overall response was 40.6% (95% CI, 24.8-56.4%). The median time to disease progression was 7.2 months (95% CI, 4.87-9.53 months). The major hematological toxicity was neutropenia. Seven patients (22.9%) developed grade 3 and 4 neutropenia, but none developed febrile neutropenia. One patient (3.1%) had grade 3 thrombocytopenia. One patient (3.1%) developed grade 3 anemia. Nausea and vomiting were seen in 12 patients (37.5%). CONCLUSIONS: The regimen of combined gemcitabine with cisplatin is safe and effective. With this combination, a lower dose of cisplatin seems to have an efficacy similar to that in previous reports.     

A phase II study of gemcitabine plus cisplatin in patients with advanced non-small cell lung cancer: clinical outcomes and quality of life.

The aim of the present phase II study was to assess the activity and safety of gemcitabine-cisplatin combination in advanced NSCLC, and to evaluate the impact of this regimen in terms of symptom benefit and quality of life (QOL). Eighty patients with pathologically confirmed advanced (stage IIIB and IV) NSCLC were enrolled into this study. Gemcitabine was administered on days 1, 8 and 15 at a dose of 1000 mg/m(2), and cisplatin was given on day 2 at a dose of 100 mg/m(2). The cycles were repeated every 4 weeks. The impact of treatment on QOL and on tumor-related symptoms was evaluated with the validated EORTC forms (QLQ-C30 and LC-13). The regimen was relatively well tolerated. Myelosuppresion was the principal toxicity. Grade 3/4 neutropenia, thrombocytopenia and anemia occurred in 58, 65 and 30% of patients respectively. In 143 cycles (35%) the administration of gemcitabine on day 15 was omitted due to myelosuppresion. Non-hematological toxicities were generally mild. Among the 76 patients available for response evaluation, there were 5 complete responses (7%) and 26 partial responses (34%); an overall response rate of 41%. The median duration of response was 8.0 months. The median survival for all 80 patients was 11.0 months and the actuarial 1-year survival probability 45%. During therapy global QOL improved in 22% of patients and particular functional domains increased in 19-37% of patients. Dyspnea was released in 36% of patients, fatigue in 45%, chest pain in 38%, shoulder pain in 27%, cough in 44%, and hemoptysis in 75%. The mean intensity scores of the last three symptoms decreased significantly with therapy. Our study confirmed relatively high efficacy of the gemcitabine-cisplatin combination in patients with advanced NSCLC. Of particular importance was that treatment with gemcitabine-cisplatin combination in a large proportion of patients was also associated with remarkable symptomatic release and with improvement of QOL. However, the high frequency of myelotoxicity-related gemcitabine omissions on day 15 of the cycle indicates that modification of the schedule should be considered in standard care.     

A phase I/II study of cisplatin and vinorelbine chemotherapy in patients with advanced non-small cell lung cancer

BACKGROUND: A combination of cisplatin and vinorelbine chemotherapy is effective in cases of advanced non-small cell lung cancer, but the optimum administration schedule for both drugs has not yet been defined. The aim of this study was to determine the maximum dose of vinorelbine that can be tolerated while receiving a fixed dose of cisplatin every 3 weeks and to observe the response in Japanese patients with advanced non-small cell lung cancer who had not previously received chemotherapy. METHODS: Cisplatin was given at a dose of 80 mg/m2 on day 1. Vinorelbine was administered on days 1 and 8 at a starting dose of 25 mg/m2 that was then increased by 5 mg/m2 increments. This treatment was repeated every 3 weeks. RESULTS: Twenty-one patients received a total of 54 chemotherapy cycles consisting of three different vinorelbine dosages. Toxicity and efficacy were evaluated in all of the patients. The main dose-limiting toxicity was neutropenia. Grades 3-4 leukopenia and neutropenia were observed in 57% and 86% of all cycles, respectively. These conditions were reversible and did not result in death from toxicity. The most severe non-hematological toxicity symptom was a grade 3 infection and reaction at the site of injection. The maximum tolerated dose of vinorelbine was 35 mg/m2. The objective response was noted in one of six patients at dose level 1, in four of 12 patients at dose level 2 and in two of three patients at dose level 3. CONCLUSION: The recommended doses were 80 mg/m2 for cisplatin and 30 mg/m2 for vinorelbine. The combination of cisplatin and vinorelbine repeated every 3 weeks is well tolerated and has shown promising anti-tumor activity against non-small cell lung cancer.     

Triplet chemotherapy with vinorelbine,gemcitabine, and cisplatin for advanced non-small cell lung cancer: a phase II study

We conducted a phase II trial of triplet chemotherapy consisting of vinorelbine, gemcitabine, and cisplatin in patients with advanced non-small cell lung cancer to assess its efficacy and toxicity. Thirty-three patients with chemotherapy-naïve stage IIIB disease (n=8), stage IV disease (n=23), or recurrence after surgical resection (n=2) were given intravenous infusions of vinorelbine 25 mg m⁻², gemcitabine 1000 mg m⁻², and cisplatin 40 mg m⁻² on days 1 and 8 at 3-week intervals. There were 16 partial responses, and the objective response rate was 48% (95% confidence interval: 31–66%). The median survival time was 13.5 months (95% confidence interval: 10.6–16.4 months), and the one-year survival rate was 61%. Grade 4 haematologic toxicity consisted of neutropenia in 72% of patients, and febrile neutropenia occurred in 42% of the patients. There was one toxic death, and it was attributed to neutropenic fever and haemoptysis. Autopsy revealed diffuse pulmonary haemorrhage secondary to bacterial abscesses and vasculitis in both lungs. The common nonhaematologic toxicities included grade 2–3 nausea (39%) and vomiting (18%). Triplet chemotherapy containing vinorelbine, gemcitabine, and cisplatin is effective in the treatment of chemo-näive patients with advanced non-small cell lung cancer, but produces unacceptable frequent febrile neutropenia.British Journal of Cancer (2002) 87, 1360–1364. doi:10.1038/sj.bjc.6600658 www.bjcancer.com© 2002 Cancer Research UK     

Combination of gemcitabine and cisplatin for advanced non-small cell lung cancer: a phase II study with emphasis on scheduling

BACKGROUND: Many regimens of gemcitabine-cisplatin chemotherapy have proven activity in patients with advanced non-small cell lung cancer (NSCLC). However, the optimal dose and schedule still have to be established. PATIENTS AND METHODS: We conducted a phase II study with administration of cisplatin 50 mg/m(2) on days 1 and 8 and gemcitabine 800 mg/m(2) on days 2, 9 and 15. This schedule was selected to optimise the synergism between the two drugs and reduce toxicity due to high dose cisplatin. RESULTS: Thirty-six chemo-naive patients with stage IIIA, IIIB or IV NSCLC entered the study (26 men, 10 women; median age 58 years, range 29-74). Twenty patients achieved a partial response: 7 out of 10 stage IIIA patients, 7 out of 13 stage IIIB patients and 6 out of 13 stage IV patients. On intent-to-treat basis, the overall response rate (RR) was 58% (95% confidence interval, 42-74%). Ninety percent of stage IIIA patients and 46% of stage IIIB patients received adjuvant surgery or radiotherapy. Overall median duration of response was 28 weeks (range 6-147 weeks). For stage IIIA, IIIB and IV patients, these numbers were 91, 13 and 23 weeks, respectively. One-year survival was 49% with 90%, 23% and 42% for stage IIIA, IIIB and IV patients, respectively. The main toxicity was myelosuppression. WHO grades 3 and 4 leukopenia occurred in 67% of patients, whereas 61% experienced grade 3 or 4 thrombocytopenia. Although hematological toxicity was clinically tolerable, it frequently led to omission of gemcitabine administration on day 15. The incidence of non-hematological toxicity was very low. CONCLUSION: This regimen of cisplatin on days 1 and 8 and gemcitabine on days 2, 9 and 15 induced a high RR in patients with advanced NCSLC. Frequent omission of gemcitabine day 15 is a limitation of this schedule. This should be an important factor in a practical approach to decide on the most optimal schedule of the cisplatin plus gemcitabine combination.     

The regimen of gemcitabine and cisplatin combined with radio frequency hyperthermia for advanced non-small cell lung cancer: A phase II study

Purpose: This phase II randomised trial was designed to evaluate the therapeutic efficacy and feasibility of radio frequency regional hyperthermia in combination with chemotherapy for patients with advanced non-small lung cancer (NSCLC).

Methods: Eighty patients with pathologically proven advanced NSCLC, were enrolled and divided into two groups. Group A patients were treated by radio frequency regional hyperthermia in combination with the regimen of gemcitabine and cisplatin (GP). Group B patients were treated with the GP regimen alone.

Results: In group A, one patient achieved a complete response (CR), 18 achieved a partial response (PR), 18 achieved a stable disease and three experienced a progression of the disease. Thirty-three patients had a positive Clinical Benefit Response (CBR). In group B, no patient achieved CR, 17 achieved PR, 19 achieved a stable disease and four experienced a progression of the disease. Nineteen patients had a positive CBR. Significant differences between the two groups were observed for the CBR (P < 0.05), but not for RR. Major toxicities included bone marrow depression, nausea, vomiting, without significant differences between the two groups (P > 0.05).

Conclusions: Radio-frequency regional hyperthermia in combination with chemotherapy (GP) is a safe, well tolerated, and effective therapeutic modality for patients with advanced NSCLC. The addition of hyperthermia improved quality of life.     

Weekly gemcitabine and cisplatin in advanced non-small-cell lung cancer: A phase II study

Background: The combination of gemcitabine and cisplatin has proven effective in the treatment of advanced non-small-cell lung cancer (NSCLC). However, the optimal schedule for administration of the two drugs has not yet been determined. In this study we evaluated the activity and toxicity of a weekly gemcitabine and cisplatin schedule.Patients and methods: Thirty-six untreated patients with stage IIIB–IV NSCLC entered the study. Treatment consisted of gemcitabine 1000 mg/m2 i.v. and cisplatin 35 mg/m2 i.v., both given weekly on days 1, 8, and 15, followed by one week of rest.Results: Ninety-seven courses (273 weekly administrations) were delivered. The median dose-intensity was 612 mg/m2 per week for gemcitabine (82%) and 21 mg/m2 per week for cisplatin (80%). All 36 of the patients were evaluable for toxicity, and 30 for response. Partial remissions were observed in 12 patients, for an overall response rate of 40% (95% confidence interval (95% CI): 22.5%–57.5%). Most of the partial remissions were seen in IIIB patients (54% of the stage IIIB and 22% of the stage IV patients responded). According to the intent-to-treat principle, the response rate was 33.3% (12 of 36 patients). The median response duration was 9.9 months (range 4–23) and the median survival time 11.8 months (range 1–24). World Health Organization (WHO) grade 3–4 myelotoxicity was: thrombocytopenia in nine patients (25%), neutropenia in six (16.6%) and anemia in six (16.6%); there was very little additional major toxicity.Conclusions: This regimen appears to be active and to have a favourable toxicity profile.     

A phase II study of vinorelbine in patients with advanced non-small cell lung cancer

Twenty-seven patients with non-small cell lung cancer were recruited into a phase II study of single-agent vinorelbine using a 25 mg/m(2) weekly dose schedule. All patients were inoperable (stage III disease - 11 patients; stage IV disease - 16 patients). Median age was 64 years (range: 37-72 years). Histological sub-types were squamous cell carcinoma (15 patients), adenocarcinoma (8) and large cell carcinoma (4). Partial response was documented in 4 (16%) of 25 evaluable patients, and stable disease in 13 (52%) patients. Median duration of response was 6.5 months (range 3-16 months) and median overall survival for patients with stable disease/partial response was 8 months (range 1-20 months). Vinorelbine was generally well tolerated although WHO grade 3/4 toxicity was noted for lethargy, constipation, alopecia (2 patients each), headache and non-tumour related bone pain (1 patient each). Vinorelbine is a moderately active single-agent in non-small cell lung cancer and is currently undergoing evaluation as part of combination chemotherapy regimens.     

A phase II study of STEALTH cisplatin (SPI-77) in patients with advanced non-small cell lung cancer.

Cisplatin-based chemotherapy improves survival in appropriately selected patients with stage IV non-small cell lung cancer (NSCLC). However, cisplatin-based regimens have well-known dose-related toxicities, particularly renal insufficiency and neurotoxicity. On the basis of prior preclinical and phase I studies, we initiated a phase II study of SPI-77 (STEALTH) Liposomal Cisplatin) in patients with stage IIIB and IV NSCLC who failed previous treatment with platinum. Disease in all subjects had progressed during therapy, failed to respond, or progressed within 3 months after discontinuing the platinum-based chemotherapy. Between January and June 1999, 13 patients were enrolled at our institution. Patient characteristics included: seven women, six men; median age, 61 years; median Karnofsky performance status, 80%; median number of prior chemotherapy regimens, two (range, 1-3). All patients had adequate hepatic and renal function. SPI-77 was administered at a dose of 260 mg/m(2) IV every 3 weeks. A median of two cycles (range 1-6) were given; the total number of cycles was 35. Among the 12 patients evaluable for response, two had (17%) stable disease and ten (83%) had progressive disease. The median survival was 24.3 weeks, and the median follow-up was 43.9 weeks. Toxicity could be evaluated in all subjects. Moderate anemia (46% of cycles, or=grade 3) with minimal granulocytopenia and thrombocytopenia (26% of cycles grade 1; 0% of cycles, >or=grade 2) were the most notable manifestations of myelosuppression. Grade 3 nonhematological toxicities included dyspnea (8%), fatigue (8%), and pain (8%). There were no grade 4 toxicities. These data suggest that this liposomal cisplatin formulation does not have appreciable activity in this population of patients with NSCLC who had received prior platinum-based chemotherapy. The lack of encouraging results from SPI-77 use in other phase I and II studies resulted in early closure of this trial by the manufacturer.     

A phase II study of single-agent gemcitabine as a second-line treatment in advanced non-small cell lung cancer

OBJECTIVE: To evaluate the efficacy and safety of the single-agent gemcitabine in advanced non-small cell lung cancer (NSCLC) as second-line chemotherapy. METHODS: Between February 2002 and November 2004, a total of 27 patients, who had previously been treated with paclitaxel and platinum as first line chemotherapy, were enrolled in the study. Patients were treated with gemcitabine (1000 mg/m(2)) on days 1, 8 and 15 in a 28 day cycle. The response was assessed every two cycles. Toxicities were evaluated according to common toxicity criteria (CTC). RESULTS: The median age was 62 (range, 46-79) years old. Among the 27 patients, 26 were male. Twenty-three patients had an ECOG performance status of 0 or 1 and four patients had a status of 2. Pathologically, 24 patients had squamous cell carcinoma and 3 had adenocarcinoma. Partial responses were observed in 15 patients. All patients were evaluated for response and toxicity. The overall response rate was 18.5% (95% confidence interval, 5-33%) and the median response duration was 17 (range, 7.4 to 49+) weeks. The median time to progression was 10 (range, 7 to 34+) weeks. The median overall survival for all patients was 38 (range, 10 to 122+) weeks. During a total of 87 cycles, granulocytopenia greater than CTC grade 2 occurred in 7%, thrombocytopenia in 1% and anemia in 24% of case. Non-hematologic toxicities were minor and easily controlled. CONCLUSION: This study confirms the activity and safety of the single-agent gemcitabine as a second-line therapy in pretreated patients with advanced NSCLC.     

NP与GP方案治疗晚期非小细胞肺癌68例疗效分析

为了评价NP和GP方案治疗晚期非小细胞肺癌的疗效和不良反应。将1999年12月2日～2004年5月2日收治的68例非小细胞肺癌（non—small cell lung cancer，NSCLC）患者随机分为两组，分别应用NP和GP方案治疗。NP方案：长春瑞滨（NVB）25mg／m^2，d1、d8；顺铂（DDP）50mg，d3～d5。GP方案：健择（Gemcitabine）1000mg／m^2，d1、d8；DDP50mg，d3～d5，两种方案均21d为1个周期，至少治疗2个周期。结果为NP组35例，无CR，PR17例（48．6％），SD13例（37．1％），PD5例（14．3％），总有效率为48．6％（17／35），临床受益率85．7％（30／35）。GP组33例，CR1例（3．0％），PR14例（42．4％），SD13例（39．4％），PD5例（15．2％），总有效率为45．5％（15／33），临床受益率84．8％（28／33）。NP组和GP组中住进展时间分别为3．2和3．3个月，初治优于复治（NP组60％vs 33％，GP组52．6％ vs 35．7％）。荆量限制性毒性主要为骨髓抑制，NP组和GP组白细胞及血小板下降的发生率分别为80％、22．9％和51．5％、51．5％。NP组静脉炎及胃肠道反应较GP组重（31．4％ vs6．1％和57．1％vs45．5％）。初步研究结果提示，NP和GP方案治疗晚期NSCLC均安全有效，疗效相当，不良反应均可耐受。     

NP与GP方案治疗晚期非小细胞肺癌68例疗效分析

为了评价NP和GP方案治疗晚期非小细胞肺癌的疗效和不良反应。将1999年12月2日～2004年5月2日收治的68例非小细胞肺癌(nonsmallcelllungcancer,NSCLC)患者随机分为两组,分别应用NP和GP方案治疗。NP方案:长春瑞滨(NVB)25mg/m2,d1、d8;顺铂(DDP)50mg,d3～d5。GP方案:健择(Gemcitabine)1000mg/m2,d1、d8;DDP50mg,d3～d5,两种方案均21d为1个周期,至少治疗2个周期。结果为NP组35例,无CR,PR17例(48.6%),SD13例(37.1%),PD5例(14.3%),总有效率为48.6%(17/35),临床受益率85.7%(30/35)。GP组33例,CR1例(3.0%),PR14例(42.4%),SD13例(39.4%),PD5例(15.2%),总有效率为45.5%(15/33),临床受益率84.8%(28/33)。NP组和GP组中位进展时间分别为3.2和3.3个月,初治优于复治(NP组60%vs33%,GP组52.6%vs35.7%)。剂量限制性毒性主要为骨髓抑制,NP组和GP组白细胞及血小板下降的发生率分别为80%、22.9%和51.5%、51.5%。NP组静脉炎及胃肠道反应较GP组重(31.4%vs6.1%和57.1%vs45.5%)。初步研究结果提示,NP和GP方案治疗晚期NSCLC均安全有效,疗效相当,不良反应均可耐受。     

A multi-institutional phase II study of combination chemotherapy with S-1 plus cisplatin in patients with advanced non-small cell lung cancer

S-1 is an oral anticancer fluoropyrimidine agent designed to elevate anticancer activity with a decrease in gastrointestinal toxicity. We conducted a phase II study to evaluate the efficacy and safety of combination chemotherapy with S-1 plus cisplatin in patients with advanced non-small cell lung cancer (NSCLC). Chemotherapy-na?ve patients were treated with S-1 administered orally at 40 mg/m(2) twice a day for 21 consecutive days, and cisplatin (60 mg/m(2)) infused intravenously on day 8, repeated every 5 weeks. Of the 44 patients enrolled in the study, 40 were assessable for efficacy and safety. The median number of cycles administered was 3 (range 1-9 cycles). Among the 40 assessable patients, 7 partial responses were observed, with an overall response rate (RR) of 17.5% [95% confidence interval (CI), 5.2-29.8]. Patients with squamous cell carcinoma showed a significantly higher RR (55.5%) than those with adenocarcinoma (9.1%) or other types of NSCLC (0%). The median progression-free survival was 4.3 months (95% CI, 3.4-4.9), the median survival time was 17.9 months (95% CI, 15.0-20.8), and the 1- and 2-year survival rates were 63.3 and 27.3%, respectively. Major grade 3-4 hematologic toxicities were leukocytopenia (7.5%), neutropenia (5.0%), anemia (15.0%) and thrombocytopenia (2.5%). No grade 4 non-hematologic toxicity or treatment-related death occurred. These results suggest that combination chemotherapy with S-1 plus cisplatin is a promising therapeutic candidate for patients with advanced NSCLC, particularly squamous cell carcinoma.     

A phase II clinical trial of gemcitabine and split dose cisplatin in advanced non-small cell lung cancer in an outpatient setting

In response to increasing pressure on inpatient services and a meta-analysis indicating that cisplatin (C) is superior to carboplatin, we report a phase II trial of gemcitabine (G) and split-dose C in advanced non-small cell lung cancer (NSCLC) in an outpatient setting. Patients with stage IIIB/IV NSCLC received: G/C 1250/40 mg/m(2); G and C were given on day (d) 1 and d8 in a 21d cycle. Patients with performance status 0-2, adequate bone marrow function and calculated glomerular filtration rate (GFR) >50 ml/min were eligible. Forty-two patients were enrolled: 25 male; median age 62 (range 37-78) years. There were 26 patients (62%) with stage IV disease. One hundred and thirty-eight cycles of chemotherapy were delivered. Chemotherapy was well tolerated, allowing maintenance of planned dose intensity (DI) with mean dose delivered of 780.1 mg/m(2) (93%) and 25.6 mg/m(2) (96%) for G and C, respectively. The overall response rate was 43%. Median survival was 12.5 months with a median follow-up of 13.5 months. One year survival rate was 51%. G plus C both given on d1 and d8 (q21d) is a very active, well tolerated and convenient outpatient schedule, which maintains DI.     

Gemcitabine plus cisplatin in the treatment of patients with advanced non-small cell lung cancer: a phase II study

BACKGROUND: Lung cancer is the leading cause of cancer death in men worldwide; most cases are not suitable for radical surgery at diagnosis and palliative treatment remains the primary goal of therapy. Cisplatin and gemcitabine are among the most active cytotoxic agents for the treatment of non-small cell lung cancer (NSCLC): they have non-overlapping toxicity and preclinical studies have demonstrated their potential synergistic interaction. PATIENTS AND METHODS: The aims of the present study were to assess the activity and tolerability of cisplatin 80 mg/m2 on day 1, combined with gemcitabine 1000 mg/m2 on days 1 and 8, administered every 3 weeks. A total of 46 consecutive patients with advanced NSCLC entered this study; all of them were evaluable for toxicity and for activity. RESULTS: According to an intent-to-treat analysis, 15 patients attained a partial response (33%), 9 (20%) obtained a disease stabilisation and 22 (47%) progressed. This regimen appeared to be modestly toxic, with grades 3-4 leukopenia and thrombocytopenia observed in 10% and 6% of cases respectively; grade 3 vomiting appeared in 12 patients (26%) and grade 3 mucositis in 1 patient. The median time-to-progression and overall survival were 200 and 400 days, respectively. CONCLUSION: Our study of gemicitabine + cisplatin on stage IV NSCLC patients achieved favourable results in terms of toxicity and overall survival.     

吉西他滨联合顺铂治疗晚期非小细胞肺癌临床分析

目的评估吉西他滨联合顺铂治疗晚期非小细胞肺癌的近期疗效和安全性。方法对33例晚期非小细胞肺癌患者采用吉西他滨1000 mg/m2,静滴,第1、8天;顺铂35 mg/m2,静滴,第1、2天。3周为1个周期,2个周期后进行一次疗效评价。结果33例患者中完全缓解(CR)0例,部分缓解(PR)14例,稳定(SD)14例,进展(PD)5例,总有效率(CR PR)为42.4%。初治优于复治(54.2%对11.1%,P=0.030)。中位疾病进展时间(TTP)5.2个月。本方案的主要毒副作用是Ⅲ/Ⅳ度血小板减少和胃肠道反应。结论吉西他滨联合顺铂3周方案治疗晚期非小细胞肺癌患者具有良好的疗效和较低的毒副作用。