Phase II study of weekly paclitaxel as second-line therapy in patients with advanced non-small cell lung cancer

A growing number of patients, mainly cisplatin-pretreated, require second-line therapy for non-small cell lung cancer (NSCLC) but the optimal treatment and appropriate criteria for patient selection have not been defined yet. A second-line phase II study was conducted in cisplatin-pretreated patients with advanced NSCLC to evaluate the activity and toxicity of weekly paclitaxel. Fifty-three consecutive NSCLC patients (9 stage IIIA-B, 44 stage IV) progressing after one front line cisplatin-based chemotherapy were enrolled. Previous treatment with taxanes was not allowed. Patients with stage III were also pretreated with thoracic radiotherapy. Weekly paclitaxel was administered as 1-h infusion at a dose of 80 mg/m(2) for three weeks with one week off, for a maximum of four courses. All patients were assessable for response, toxicity and survival. A complete response was observed in one case, partial response in 7, for an overall response rate (RR) of 15%, (95% Cl = 5-25%). Stable disease (SD) was registered in 11 patients, for an overall clinical benefit (CB = RR + SD) of 36% (95% Cl = 23-49%). Toxicity was mild, with G3-4 neutropenia and thrombocytopenia in 6 and 2% of patients, respectively. Non-hematological toxicities were negligible. No significant correlation between patient or treatment-related variable and RR was observed. CB was significantly higher in patients with non-squamous histology (P = 0.03) and no progression within 4 months of first line cisplatin-based chemotherapy (P = 0.007). Median progression-free survival (PFS) was 7 months in responders and 4 months in pts with SD. PFS was significantly related to good performance status (PS) (P = 0.002) and non-squamous histology (P = 0.004). In conclusion, weekly paclitaxel has acceptable palliative activity and excellent tolerance in cisplatin-pretreated patients. Patients with PS 0-1, non-squamous histology and with no progression within 4 months of first line cisplatin-based chemotherapy seem more likely to benefit from this treatment.     

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.     

A phase II study of S-1 monotherapy as second-line treatment for advanced non-small cell lung cancer

Purpose  To assess the efficacy and toxicity of an oral anticancer fluoropyrimidine derivative, S-1, for previously treated patients with advanced non-small cell lung cancer (NSCLC). Patients and methods  Patients with advanced (clinical stage IIIB-IV) NSCLC who had previously received one platinum-based chemotherapy were enrolled. S-1 was administered orally at the dosage decided by using the nomogram based on patient BSA b.i.d. for 28 consecutive days, repeated every 6 weeks. Results  Between August 2005 and July 2007, 50 patients were entered into this study. Six patients achieved partial response (PR), and the overall response rate of eligible patients was 12.5% (6/48) (95% confidence interval (95%CI), 3.1–21.9%). Disease control rate was 39.6% (19/48) (95%CI, 25.7–53.4%). Median progression-free survival was 2.5 months. Median survival time was 8.2 months, and 1-year survival rate was 29.6%. No grade 4 toxicities were encountered. Grade 3 hematological toxicities comprised neutropenia in one patient (2.1%) and anemia in one patient (2.1%). Grade 3 non-hematological toxicities were observed in only five patients (10.4%). Treatment-related death did not occur. Conclusion  S-1 is an active and well-tolerated monotherapy for second-line treatment of advanced NSCLC.     

Weekly docetaxel as second-line therapy in non-small cell lung cancer: a phase II study

INTRODUCTION: Single-agent docetaxel is active as second-line chemotherapy in non-small cell lung cancer (NSCLC) pretreated patients; seven phase II studies have shown response rates of about 20% and 9 months of median survival. Two phase III studies documented a survival benefit at 1 year compared to BSC and vinorelbine or ifosfamide. Recent trials indicate acceptable activity and a good safety profile of weekly docetaxel with doses of 25-43 mg/m2. The aim of our study was to confirm this evidence and to evaluate activity and toxicity of weekly docetaxel at the dose of 40 mg/m2. PATIENTS ATND METHODS: Twenty-one patients with NSCLC entered the study (7 stage IIIB and 14 stage IV): 13 males and 8 females. Median age was 66 years (range, 53-75). ECOG was O in 6, 1 in 9 and 2 in 6 patients. All patients were pretreated with a first-line chemotherapy (13 patients progressed soon after the first line); 6 of them received palliative radiotherapy on the chest. The treatment consisted of weekly docetaxel, 40 mg/m2 in 1 hr for six weeks with two weeks of rest (1 cycle). A total of 87 administrations was delivered (median, 4; range, 1-12). RESPONSES: All patients were assessable for response (according to the "intent-to-treat principle") and for toxicity. No complete or partial remission was observed; 2 minor responses (9.5%), 1 stable disease (5%), 8 progressive diseases (38%) were documented. Seven patients dropped out the study due to severe toxicity (33.5%) and 3 due to early death (14%). Median survival was 3 months (range, 1-17), and 1-year survival was 9.5%. Toxicity was as follows: grade 4 diarrhea in 1; grade 3 asthenia in 8 (38%), grade 3 stomatitis in 2; grade 3 neutropenia in 1; allergic reactions in 2. No treatment-related death was recorded. CONCLUSIONS: The trial showed only very modest activity of weekly docetaxel, with severe side effects that induced us to stop the accrual in order to prevent other worse toxicities. We therefore concluded that a dose of 40 mg/m2 of weekly docetaxel is not manageable and does not seem to provide a real benefit in terms of response and quality of life.     

A phase II pharmacodynamic study of erlotinib in patients with advanced non-small cell lung cancer previously treated with platinum-based chemotherapy

PURPOSE: To examine potential markers of clinical benefit and the effects of erlotinib on the epidermal growth factor receptor (EGFR) signaling pathway in advanced non-small cell lung cancer patients refractory to platinum-based chemotherapy. EXPERIMENTAL DESIGN: Patients were given erlotinib (150 mg/d). Tumor biopsies were done immediately before treatment and in a subgroup of patients after 6 weeks' treatment. RESULTS: Of 73 evaluable patients, 7 (10%) had partial response and 28 (38%) had stable disease. In 53 patients with baseline tumor samples, no relationship was observed between pretreatment levels of EGFR, phosphorylated (p)-EGFR, p-AKT, p-mitogen-activated protein kinase (MAPK), or p27 and clinical benefit (i.e., response, or stable disease >/=12 weeks). Tumors from 15 of 57 patients had high EGFR gene copy number, assessed using fluorescence in situ hybridization (FISH positive), 10 of whom had clinical benefit, compared with 5 of 42 FISH-negative patients. FISH-positive patients had longer median progression-free [137 versus 43 days, P = 0.002; hazard ratio (HR), 0.37] and overall (226 versus 106 days, P = 0.267; HR, 0.70) survival than FISH-negative patients. In paired biopsy samples from 14 patients, p-EGFR (P = 0.002), p-MAPK (P = 0.001), and Ki-67 (P = 0.025) levels were significantly reduced after 6 weeks' treatment. Apoptosis was significantly increased in patients with clinical benefit (P = 0.029), and may be a marker of clinical benefit. CONCLUSION: In this study, EGFR FISH-positive status was associated with improved outcome after erlotinib therapy. Erlotinib led to reduced levels of p-EGFR, p-MAPK, and Ki-67, and stimulated apoptosis in tumor samples from patients with clinical benefit.     

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 pharmacokinetic and phase II study of gallium nitrate in patients with non-small cell lung cancer

This study investigated the pharmacokinetics and activity of gallium nitrate in non-small cell lung cancer when 700 mg/m² was given as a 30-min infusion with prehydration every 2 weeks. Gallium was measured in plasma and urine using flameless atomic absorption spectrophotometry, and pharmacokinetics of total and ultrafilterable gallium were calculated. Twenty-five patients with non-small cell lung cancer received 1–12 (median 2) courses of gallium nitrate every 2 weeks. Of 21 patients evaluable for response, 1 partial response was recorded, 4 patients had stable disease, and 16 had progressed. The most serious toxicities were renal impairment and optic neuritis. Hypocalcaemia was recorded in 3 patients. The mean C_max was 15.2 ± 3.1 μg/ml (range 9.5–21.2). Most gallium remained ultrafilterable for the first 10 h, after which plasma protein binding increased, and at 48 h only 11% was present as ultrafilterable gallium. The elimination profiles of both total and ultrafilterable gallium were biphasic, and the distribution phase consisted of ultrafilterable gallium, with a distribution half-life of 1.4 h. Total gallium plateaued at 1.9 μg/ml at between 8 and 12 h, and the estimated elimination half-life was 63 h. The elimination half-life of ultrafilterable gallium was 16.5 h. Inter- and intra-patient variability in pharmacokinetics was minimal. A mean of 50 ± 14% of the gallium dose was excreted in the urine within 48 h. A short infusion of gallium nitrate achieving high peak plasma concentrations results in little efficacy in non-small cell lung cancer. Received: 5 March 1999 / Accepted: 24 May 1999     

Antiangiogenic agents as second-line therapy for advanced non-small cell lung cancer

With the approval of the antiangiogenic antibody bevacizumab in non-small cell lung cancer (NSCLC) and other malignancies, the tumor vasculature has emerged as a worthwhile therapeutic target. Second-line therapies have the potential to improve overall survival and quality of life over best supportive care alone. Accordingly, phase II and phase III studies are actively evaluating antiangiogenic treatments in the second-line setting in NSCLC, and results are awaited. Such therapies include antiangiogenic antibodies, small molecule inhibitors, and vascular-disrupting agents. This review will present the current landscape of angiogenesis inhibition in NSCLC, focusing on use as second-line therapy.     

Low-dose weekly paclitaxel as second-line treatment for advanced non-small cell lung cancer: a phase II study

PURPOSE: To assess the activity and toxicity of low-dose weekly paclitaxel in patients with non-resectable or metastatic non-small cell lung cancer (NSCLC) and who had disease recurrence or failure with previous chemotherapy. PATIENTS AND METHODS: Forty patients with NSCLC previously treated with platinum-based chemotherapy received weekly paclitaxel 80 mg/m(2) as a 1 h infusion. The median age was 63 years (range 42-77 years); 25 patients had Eastern Cooperative Oncology Group performance status (PS) 1 and 15 had PS 2. Thirty-one patients had stage IV disease and nine stage III (eight stage IIIB and one stage IIIA). RESULTS: A total of 364 weeks of treatment were administered (median 8 weeks, range 2-17 weeks). There were no episodes of grade 3 or 4 haematological toxicities. Severe non-haematological toxicity was uncommon: grade 1-2 asthenia in 50%; grade 1-2 motor neuropathy in 45% and grade 3 in 10%; grade 1-2 sensory neuropathy in 62% of patients. Alopecia was mild. The overall response rate was 37.5% (95% CI, 23.9-55): 2 CR, 13 PR, 15 SD, 8 PD, 2 NE. Median overall survival was 9.7 months (95% CI, 6.5-12.8). Median time to progression was 5.4 months (95% CI, 1.8-8.9). CONCLUSION: A low-dose weekly paclitaxel regimen had good clinical efficacy with low toxicity in this group of patients with poor prognosis. This regimen increases the therapeutic options available for second-line therapy in NSCLC patients.     

A multi-center phase II study of nintedanib as second-line therapy for patients with advanced non-small-cell lung cancer in China

Purpose: This study examined the efficacy and safety of using nintedanib as single-regimen in 2^nd-line chemotherapy for Chinese patients with advanced (beyond stage IIIB) non-small-cell lung cancer (NSCLC). Methods: Chinese patients were those with stage IIIB or IV NSCLC and had unsuccessful 1^st-line platinum based chemotherapy. Patients received two oral intakes of 200 mg nintedanib everyday from day 1 to day 21, on every 4-week cycle. Primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS) and disease control rate. Results: There were 62 eligible patients enrolled in the study. Half of the patients were male (n = 31, 50.0%). The median age was 64.2 years with youngest age of 33 years and oldest age of 83 years. Median PFS was 3.9 months (95% CI, 2.7-6.4 months). Median OS was 6.7 months (95% CI, 4.8-10.1 months). No patients (0.0%) had complete response. Thirty-one patients (50.0%) had stable disease and 23 patients (37.1%) had partial response. The most common severe adverse events (AEs), graded as 3 or 4, were heart failure (n = 12, 19.4%), hypertension (n = 7, 11.8%) and diarrhea (n = 6, 9.8%). Conclusion: NSCLC Patients in 2^nd-line chemotherapy reached similar PFS, as compared with other FDA-approved second-line regimens. Also, the toxicity of nintedanib was well tolerated. Thus, nintedanib may be used as a standard regimen for 2^nd-line chemotherapy for patients with advanced NSCLC.     

Cisplatin and weekly docetaxel as first-line therapy in patients with advanced non-small cell lung cancer a phase II study

BACKGROUND: Based on the results of previous phase I studies, in the current phase II trial we evaluated the efficacy and toxicity of cisplatin plus weekly docetaxel in the treatment of advanced non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: The eligibility criteria for the study included newly diagnosed stage IIIB/IV NSCLC, age < or = 75 years, Eastern Cooperative Oncology Group performance status of 0-2, adequate organ functions, and signed informed consent. The chemotherapy regimen consisted of cisplatin, 80 mg/m2 on day 1, and docetaxel, 25 mg/m2 on days 1, 8 and 15 every 4 weeks. RESULTS: Between January 2002 and December 2003, 31 patients with NSCLC were enrolled in the study. An objective response rate of 40% (95% CI, 21-60) was obtained in 27 assessable patients. The median time to progression was 6.4 months (range, 2.5-26.3) and median overall survival was 10.01 months (range, 5-28.3). The regimen was well tolerated with no grade 4 toxicity. CONCLUSIONS: Cisplatin plus weekly docetaxel is an effective and well-tolerated regimen in chemo-naive patients with advanced NSCLC. A phase III study of weekly versus the conventional regimen of every three weeks should be conducted to compare the survival benefits, toxicity profile and quality of life.     

多西他赛二线治疗23例晚期非小细胞肺癌

目的：评价单药多西他赛[泰索帝)作为二线化疗耐晚期非小细胞肺癌(NSCLC)的疗效和不良反应，方法：23例经病理和(或)细胞学诊断的晚期非小细胞肺癌．曾用含铂类方案化疗，治疗后复发或进展．接受泰素帝75mg/m^2静滴1小时．第1天．每3周重复。结果：可评价疗效23例中．无完全缓解（CR)，部分缓解(PR）17％(4／23)，稳定(SD)57％(13／23)，进展(PD)26％(6／23)，有效率17％(4／23)；中位生存期9个月，一年生存率39％(9，23)。不良反应主要是血液学毒性，但患者可以耐受。结论：泰素帝草药用于二线化疗治疗晚期非小细胞肺癌疗效肯定．耐受性较好。     

A phase II study of weekly paclitaxel in elderly patients with advanced non-small cell lung cancer.

PURPOSE: Our aim was to evaluate the efficacy, toxicity, and pharmacokinetic behavior of single-agent paclitaxel given weekly to elderly patients with lung cancer. EXPERIMENTAL DESIGN: Previously untreated patients with stage IIIB/IV non-small cell lung cancer were eligible for the study if they were at least 70 years of age and had preserved organ function. Paclitaxel was administered over 1 h at a dose of 90 mg/m(2) for 6 consecutive weeks on an 8-week cycle. The pharmacokinetics of paclitaxel were assessed during the first and sixth week of therapy in a subgroup of eight patients. RESULTS: A total of 35 patients (median age, 76 years; range, 70-85) were enrolled. The overall response rate was 23%. Median time to failure was 5.2 months, whereas the median survival time was 10.3 months. Survival rates after 1 and 2 years were 45 and 22%, respectively. Grade 3/4 toxicities included neutropenia (5.8%), hyperglycemia (17.6%), neuropathy (5.8%), and infection (8.8%). Two patients died from treatment-related toxicity. There was no significant difference (P = 0.18) between the total body clearance of paclitaxel on the first (17.4 +/- 2.9 liters/h/m(2), mean +/- SD) and sixth (15.8 +/- 4.1 liters/h/m(2)) week of therapy. CONCLUSION: Paclitaxel administered as a weekly 1-h infusion at a dose of 90 mg/m(2) is a safe and effective therapy for elderly patients with advanced non-small cell lung cancer. Its pharmacokinetics in elderly patients do not appear to differ from historical data for younger patients, and there was no suggestion of a change in drug clearance after repeated weekly dosing.     

A phase II study with gemcitabine and split-dose cisplatin in patients with advanced non-small cell lung cancer

BACKGROUND: The combination of gemcitabine and cisplatin is among the most active regimens for the treatment of NSCLC. However, the optimal dose and schedule for administration of the two drugs has not yet been determined. We investigated the activity and toxicity of a gemcitabine and split-dose cisplatin regimen in an outpatient setting for patients with advanced non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: From June 2004 to May 2005 patients with stage IIIB or IV who had not had prior chemotherapy entered the study. Treatment consisted of gemcitabine 1250 mg/m2 and cisplatin 35 mg/m2, both given intravenously on days 1 and 8 every 21 days. RESULTS: Forty-five patients were entered this study. Patient characteristics were as follows: male/female, 34/11; median age (range), 62 (30-76) years; ECOG PS 0/1/2, 7/30/8; stage IIIB/IV, 18/27. A total of 168 cycles were delivered, with a median of 4 cycles (range, 1-6). All patients were evaluable for toxicity. Grade 3 and 4 toxicities according to the NCI toxicity criteria included neutropenia in 8 patients (18%), anemia in 4 (9%), thrombocytopenia in 7 (15%), and emesis in 1 (2%). Of 42 patients assessable for response, 23 patients showed a partial remission. On intent-to-treat basis, the overall response rate was 51% (95% CI, 37-65%). Median time to progression was 6.0 months (range, 1.2-12.0 months) and median overall survival was 13.1 months (range, 1.4-17 months). CONCLUSIONS: This regimen with gemcitabine and split-dose cisplatin using a 21-day schedule appears to be active and very well-tolerated in an outpatients setting for patients with advanced NSCLC.     

多西他赛或表皮生长因子受体酪氨酸激酶抑制剂二线治疗晚期非小细胞肺癌的临床观察

目的 观察多西他赛或表皮生长因子受体酪氨酸激酶抑制剂（epidermal growth factor receptor tyrosine kinase inhibitors,EGFR-TKIs）二线治疗晚期非小细胞肺癌（non-small cell lung cancer,NSCLC）的临床疗效及安全性。 方法 回顾性分析2009年1月至2013年6月接受多西他赛或EGFR-TKIs二线治疗晚期NSCLC患者的临床资料,对符合入组标准的100例进行观察和分析,其中52例接受EGFR-TKIs治疗（TKIs组）,48例接受多西他赛治疗（DOC组）。采用Kaplan-Meier方法计算两组患者的中位无疾病进展生存时间（mPFS） 、中位总生存时间（mOS）,并行Log-rank检验。结果 TKIs组、DOC组患者二线治疗后mPFS分别为6个月、3个月（P=0.021）;mOS分别为16个月、10个月（P=0.068）;客观有效率（ORR）分别为23.1％、6.3％（P=0.038）。DOC组Ⅲ~Ⅳ级白细胞减少、中性粒细胞减少及其引起发热的发生率明显高于TKIs组（P均＜0.001）。结论 临床上对具有EGFR敏感突变潜在临床特征的晚期NSCLC患者进行二线治疗时,EGFR-TKIs比多西他赛治疗能显著延长患者中位无疾病进展生存时间,毒副反应较少,具有更高的安全性。     

Second-line therapy with gefitinib in combination with docetaxel for advanced non-small cell lung cancer: a phase II randomized study

This randomized, open-label, parallel-group, phase II study evaluated the efficacy and safety of gefitinib and docetaxel in combination, as second-line therapy for advanced or metastatic non-small cell lung cancer (NSCLC). Eighty-nine patients who had failed first-line, platinum-based chemotherapy were randomly assigned to gefitinib (250 mg/day orally) in combination with docetaxel (75 mg/m² every 3 weeks) or single-agent docetaxel (75 mg/m² every 3 weeks). Objective response rates were 6.8% with gefitinib plus docetaxel and 9.1% with docetaxel alone. Disease control was experienced by a higher proportion of patients receiving gefitinib plus docetaxel (59.1%) versus docetaxel alone (34.1%). Median progression-free and overall survival appeared to be longer with gefitinib plus docetaxel (3.9 months [95% CI:2.3–5.4] and 7.6 months [95% CI:5.4–10.4], respectively) than with docetaxel alone (2.1 months [95% CI:2.1–3.7] and 6.2 months [95% CI:5.2–7.2], respectively). The most common non-hematological adverse events were diarrhea, alopecia, rash and dry skin in the combination arm, and vomiting and asthenia with docetaxel alone. Gefitinib and docetaxel combination therapy has antitumor activity and may be a feasible treatment option in patients with advanced NSCLC who have failed platinum-based chemotherapy.     

A phase II study of bryostatin-1 and paclitaxel in patients with advanced non-small cell lung cancer

BACKGROUND: Bryostatin-1 is a macrocyclic lactone, which exhibits pleiotropic biological effects via protein kinase C and has shown preclinical synergy with paclitaxel for enhanced tumor cell apoptosis. PATIENTS AND METHODS: Patients had stage IIIB (pleural effusion)/IV non-small cell lung cancer, measurable disease, performance status 0-2 Eastern Cooperative Oncology Group, adequate organ function, and no prior chemotherapy. Patients received dexamethasone premedication followed by paclitaxel at a dose of 90 mg/m(2) on days 1, 8, and 15 along with bryostatin-1 50 microg/m(2) on days 2, 9, and 16 every 28 days until disease progression. Correlative assays measuring serum levels of tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), and T-lymphocyte numbers were performed based on a previous study showing cytokine induction in vivo by bryostatin-1. Fifteen patients were enrolled. RESULTS: Thirty cycles of the bryostatin-1 and paclitaxel were delivered with a median of 2 per patient (range 1-4). Myalgia was the predominant non-hematologic toxicity encountered as 3 patients developed grade 4 and 1 patient developed grade 3 myalgia. Four patients were removed from the study during cycle 1 for rapid disease progression or myalgia. Eleven patients could be evaluated for response. Five patients had stable disease, two had a mixed response, and four had progressive disease. Ten patients received second-line chemotherapy after leaving the study. Median survival was 31 weeks (95% confidence interval: 5.4-49.3). Correlative data showed a trend towards decreased plasma IL-6 and TNF-alpha after each cycle of therapy presumably due to the dexamethasone premedication and/or paclitaxel. CONCLUSIONS: This drug combination showed no significant clinical response and was associated with reproducible toxicity. The predominance of myalgia in the absence of elevated serum cytokines suggests a non-inflammatory etiology of this toxicity.     

Phase II study of cisplatin-combined schedules as second-line chemotherapy in patients with non-small cell lung cancer

BACKGROUND: The aim of this study was to evaluate the effectiveness of cisplatin- (CDDP) combined chemotherapy in non-cisplatin pretreated patients with non-small-cell lung cancer (NSCLC). The second cytotoxic drug administered was either etoposide or gemcitabine. First-line treatment was based on paclitaxel combined with either carboplatin or vinorelbine. PATIENTS AND METHODS: Seventy-eight patients with histologically- or cytologically- confirmed NSCLC, having failed front-line treatment, were enrolled. All patients received 80 mg/m2 of cisplatin as second-line treatment, on day 1, repeated every 3 weeks; in 48 patients the second agent was etoposide (120 mg/m2) on days 1, 2 and 3, repeated every 3 weeks and in 30 patients 1 g/m2 of gemcitabine on day 1, repeated every 3 weeks. RESULTS: All patients were evaluable for response and toxicity. No complete responses were observed. Thirteen (16.67%) patients achieved partial response, 42 (53.85%) stable disease and 23 (29.49%) had disease progression. The median duration of response was 4 months (range 2-8+ months), median time to tumor progression (TTP) 5 months (range 2-9 months) and median survival time after starting second-line chemotherapy, 6 months (range 2-9+ months). Toxicity was acceptable: 9 patients presented with nephrotoxicity (11.54%) and 13 (16.67%) with grade 3-4 neutropenia. CONCLUSION: The cisplatin combination as second-line treatment in patients with NSCLC exhibited a notable degree of activity and tumor growth control was evidenced by the 16.67% partial response and 53.85% disease stability.     

多西紫杉醇联合长春瑞滨二线治疗晚期非小细胞肺癌的临床研究

Objective:To evaluate the efficacy and toxicity of docetaxel and vinorelbine as second-line chemotherapy in the treatment of advanced non-small cell lung cancer (NSCLC).Methods:48 histologically or cytologically confirmed NSCLC patients with progressive or recurrent disease after first-line treatment were treated with docetaxel and vinorelbine.The chemotherapy included vinorelbine (25 mg/m2) on days 1,5 and docetaxel (60 mg/m2) on day 1.The treatment was repeated every 3 weeks.Patients receiving at least two cycles were evaluated for efficacy and toxicity.Results:Of 48 patients,1 patient achieved complete response and 16 achieved partial response.Overall response rate for all 48 patients was 35.4% (17/48).Main hematologic toxicities included neutropenia (60.4%) and febrile neutropenia (29.2%) and non-hematologic toxicities were mild.Conclusion:The combination of docetaxel-vinorelbine as second-line chemotherapy is an effective regimen with manageable toxicity for the treatment of advanced NSCLC.Further studies may confirm these results.