Chemotherapy of advanced non-small-cell lung cancer: a randomized trial of three cis-platin-based chemotherapy regimens

One hundred fifty-two patients with locally advanced or metastatic non-small-cell lung cancer were randomized to receive treatment with one of three cis-platin-containing chemotherapy regimens: vindesine/cis-platin, etoposide/cis-platin, or vindesine/etoposide/cis-platin. Following an 8-week induction course of treatment, patients were evaluated for response; responders continued to receive monthly chemotherapy. All patients were followed until death. Response rates for the three regimens were 10%, 6%, and 24%, respectively; the cis-platin/vindesine/etoposide regimen produced more responses than did either cis-platin/etoposide or cis-platin/vindesine (p less than 0.05). However, median survival was not improved with the three-drug regimen, and myelosuppression produced by this regimen was worse. The 20-week median survival for the entire group suggests that these treatments had no impact on survival. None of these regimens can be recommended for routine treatment of patients with advanced non-small-cell lung cancer. The addition of vindesine did not make a significant impact in response rate or overall survival in this study.     

Docetaxel versus docetaxel plus cisplatin as front-line treatment of patients with advanced non-small-cell lung cancer: a randomized, multicenter phase III trial.

PURPOSE: To compare the overall survival (OS) of patients with advanced non-small-cell lung cancer (NSCLC) treated with docetaxel plus cisplatin (DC) or docetaxel (D) alone. PATIENTS AND METHODS: Chemotherapy-na?ve patients with advanced/metastatic NSCLC were randomly assigned to receive either DC (n = 167; docetaxel 100 mg/m(2) on day 1, cisplatin 80 mg/m(2) on day 2, and recombinant human granulocyte colony-stimulating factor (rhG-CSF) 150 microg/m(2)/d on days 3 to 9) or D (n = 152; 100 mg/m(2) on day 1 without rhG-CSF) every 3 weeks. RESULTS: The overall response rates were 36.5% for DC (three complete responses and 58 partial responses) and 21.7% for D (one complete response and 32 partial responses; P =.004). The median OS was 10.5 months (range, 0.5 to 41 months) and 8.0 months (range, 0.5 to 41 months) for DC and D, respectively (P =.200). The 1- and 2-year survival rates were 44% and 19% for DC and 43% and 15% for D, respectively. Median times to tumor progression were 4.0 and 2.5 months for DC and D, respectively (P =.580). Grade 2/3 anemia was significantly higher with DC than with D (33% v 16%; P =.0001). Fifteen (9%) DC and 12 (8%) D patients developed febrile neutropenia. Grade 3/4 nausea/vomiting (P =.0001), diarrhea (P =.007), neurotoxicity (P =.017), and nephroroxicity (P =.006) were significantly more common with DC than with D. There were five treatment-related deaths in the DC group and one in the D (P =.098). CONCLUSION: DC regimen resulted in a higher response rate but without improvement in median time to tumor progression or OS compared with D. D could be a reasonable front-line chemotherapy for patients who cannot tolerate cisplatin.     

Front-line paclitaxel-vinorelbine versus paclitaxel-carboplatin in patients with advanced non-small-cell lung cancer: a randomized phase III trial.

PURPOSE: This randomized phase III trial of advanced or metastatic non-small-cell lung cancer (NSCLC) was designed to compare a standard treatment such as carboplatin (CRP)-paclitaxel (PCT) with a new combination, vinorelbine (VRL)-PCT-two agents acting in microtubules. PATIENTS AND METHODS: Three hundred and sixty patients (stage IIIa, IIIb and IV) were included and evaluated for response rate, survival and toxicity. Arm A patients were treated with the control combination of CRP 6 AUC and PCT 175 mg/m(2) repeated every 3 weeks for six cycles, and arm B with the investigational combination of VRL 25 mg/m(2) and PCT 135 mg/m(2) repeated every 2 weeks for nine cycles. The patients were well balanced with respect to gender, disease stage and performance status. Arm A received 849 cycles (mean 4.59 per patient) and arm B 951 cycles (mean 5.39 per patient). RESULTS: Complete and partial response rates were 45.95% and 42.86% for arms A and B, respectively. Median survival was 11 and 10 months, 1-year survival 42.7% and 37.85% and 2-year survival 10.12% and 19% for arms A and B, respectively. Toxicity was similar in all patients, except for neutropenia, which was significantly greater in arm B. CONCLUSIONS: PCT combined with VRL produces similar (non-significant) response rates, survival and toxicity (except for neutropenia, as noted above) to standard CRP-PCT treatment in untreated advanced-stage NSCLC.     

非小细胞肺癌化疗、放疗联合治疗的进展

支气管肺癌的治疗方法和其他实体肿瘤一样,包括手术治疗、放射治疗(放疗)、化学治疗(化疗)、中医中药治疗,还有近日发展蓬勃的生物靶点治疗。肺癌中80%以上为非小细胞肺癌(NSCLC),不可手术的中晚期、晚期肺癌占了大多数,内约半数为局部广泛期的ⅢA、ⅢB期,其主要治疗方法为放疗,放疗技术发展历经50年,已从凭经验发展成为有理论根据的新学科。20余年来,随化疗的发展及其兼有全身、局部及增敏作用的特点,化放疗联合发展为局部广泛期的规范治疗方案,然而如何应用有关化放疗的作用机制,以求发挥其最大作用提高疗效,减低毒性是关键所在。为此,…     

Long-term chemotherapy may prolong survival in advanced non-small-cell lung cancer among responders to first-line chemotherapy

Survival in patients with advanced non-small-cell lung cancer (NSCLC) has substantially improved. Long-term chemotherapy with epidermal growth factor tyrosine kinase inhibitors (EGFR-TKIs) and other agents has been associated with long survival. We retrospectively examined the associations between overall survival (OS) and clinical variables in patients with advanced NSCLC who received at least one dose or course of outpatient chemotherapy in our institution. Of 360 patients who received first-line chemotherapy between January 1, 2004 and December 31, 2007, 185 subsequently received additional outpatient chemotherapy and 175 underwent inpatient chemotherapy only. Of the 185 patients, 147 (79.5%), 96 (51.9%), and 60 (32.4%) received second-line, third-line, and fourth-line chemotherapy, respectively. Patients who received outpatient chemotherapy had significantly longer median OS (22.3 months) than did those undergoing inpatient chemotherapy only (7.6 months; P < 0.0001). In univariate analysis of the 185 patients, sex, performance status (PS), smoking status, stage, best response to first-line chemotherapy, use of docetaxel, and EGFR-TKIs were significantly associated with OS (P values: 0.0019, 0.0066, 0.0001, 0.0231, 0.0011, 0.0250, and 0.0023, respectively). In multivariate analysis, PS, stage, best response to first-line chemotherapy, and use of docetaxel were significantly associated with OS (P values: 0.0272, 0.0030, 0.0022, and 0.0376, respectively). Survival was significantly longer among patients who responded to docetaxel and/or EGFR-TKIs. Long-term chemotherapy did not increase cumulative hospitalization. In patients with advanced NSCLC, an effective long-term chemotherapy regimen might prolong survival in responders to first-line chemotherapy.     

Bi-weekly administration of gemcitabine plus vinorelbine in elderly patients with advanced non-small-cell lung cancer: multicenter phase II trial

PURPOSE: Gemcitabine (GEM) and vinorelbine (VNR) have demonstrated activity as a first-line treatment in elderly patients with advanced non-small-cell lung cancer (NSCLC). We conducted a multicenter phase II trial to evaluate the efficacy and toxicity of bi-weekly administration of GEM plus VNR in elderly patients with advanced NSCLC. PATIENTS AND METHODS: Forty-six chemotherapy-naive elderly (age: >or=70 years) NSCLC patients were enrolled. Patients were eligible if they had histologically or cytologically confirmed unresectable NSCLC with measurable and/or assessable disease. Patients received GEM (1000 mg/m2) and VNR (25 mg/m2) every 2 weeks. RESULTS: The objective response rate of this treatment was 22.7% (95% confidence interval (CI), 10.3-35.1%), median survival time was 310 days, and median time to progression was 133 days. The one-year survival rate was 40.9% (95% CI, 26.3-55.4%), and most adverse events were mild. Only three (6.8%) patients needed to omit GEM because of grade 4 neutropenia or due to physician judgment. No patients suffered treatment-related death. CONCLUSIONS: Bi-weekly administration of GEM plus VNR in elderly patients was an effective, feasible and well-tolerated treatment schedule.     

老年人晚期非小细胞肺癌化疗疗效及预后分析

目的探讨年龄≥65岁的晚期非小细胞肺癌（NSCLC）患者含铂方案化疗疗效及预后因素。方法回顾性分析70例年龄≥65岁的ⅢA～Ⅳ期NSCLC患者一线含铂方案化疗疗效及不良反应;Kaplan—Meier法分析生存情况,COX回归法进行多因素预后分析。结果全组中位化疗数为3个周期,共有53例患者可评价疗效,总有效率41．5％（22／53）,且疗效不受年龄影响（X^2=1．945,P=0．378）;中位无进展生存时间6．0个月,中位生存时间12．5个月;化疗相关血液毒性发生率高;多因素分析提示ECOG评分、远处器官转移数目、化疗周期数是影响预后的独立因素。结论老年晚期NSCLC患者一线含铂方案化疗具有较高疗效,但不良反应发生率高,化疗耐受性较差,合理选择患者是关键;ECOG评分差、多发远处器官转移患者难以从化疗中获益;而对于可耐受化疗患者,3—6周期化疗可明显改善预后。     

Postprogression survival for first-line chemotherapy of patients with advanced non-small-cell lung cancer

BackgroundGiven the growing number of drugs available for non-small-cell lung cancer (NSCLC), an effect of first-line chemotherapy on overall survival (OS) might be confounded by subsequent therapies. We examined the relation between postprogression survival (PPS) and OS in phase III trials of first-line chemotherapy for advanced NSCLC.Patients and methodsA literature search identified 69 trials that were published during the past decade. We partitioned OS into progression-free survival (PFS) and PPS and evaluated the relation between OS and either PFS or PPS. We also examined whether any association might be affected by the year of completion of trial enrollment.ResultsThe average PPS was longer in recent trials than in older trials (6.5 versus 4.4 months, P < 0.0001). For all trials, PPS was strongly associated with OS (r = 0.82), whereas PFS was moderately associated with OS (r = 0.43). The correlation between OS and PPS in recent trials was stronger than that in older trials (r = 0.89 and 0.66).ConclusionsOur findings indicate that, especially for recent trials, PPS is highly associated with OS in first-line chemotherapy for advanced NSCLC, whereas PFS is only moderately associated with OS.     

A study of postoperative radiotherapy in patients with non-small-cell lung cancer: a randomized trial

PURPOSE: To study the value of postoperative radiotherapy for non-small-cell lung cancer (NSCLC) with positive regional lymph metastases (NI or N2) after radical surgery. MATERIALS AND METHODS: From February 1982 to October 1995, 366 patients with NSCLC and N1 or N2 disease were randomized into postoperative radiotherapy (S + R) (183 patients) and no further treatment (S alone) (182 patients). Postoperative radiotherapy (RT) was administrated 3-4 weeks after radical operation. Irradiated fields covered the bronchial stump, ipsilateral hilum, and most of the mediastinum. The midplane dose was 6000 cGy/30 fractions/6 weeks, with the spinal cord limited to 4000 cGy/20 fractions/4 weeks or less. One hundred thirty-four patients in S + R group and 162 patients in S alone group were evaluated. Clinical data were comparable in both arms, except for the numbers of N2 patients. RESULTS: The 3-year and 5-year overall survival rates were 51.9% and 42.9% in the S + R group and 50.2% and 40.5% in the S alone Group (p = 0.56). The 3-year and 5-year disease-free survival rates were 50.7% +/- 4.7% and 42.9% +/- 5.2% in the S + R group vs. 44.4% +/- 4.3% and 38.2% +/- 4.5% in the S alone group (p = 0.28), respectively. In the patients with NI or T3-4 tumors, there was a trend toward improved survival in the S + R group, especially in the patients with T3-4N1M0. These patients demonstrated 20% improvement in overall survival (p = 0.092) and greater than 20% better disease-free survival (p = 0.057). Postoperative RT reduced local recurrence but had no impact on distant metastases. CONCLUSION: Postoperative RT significantly reduced local relapses, but did not improve overall survival, due to a high frequency of distant metastases in this patient group.     

Front-line treatment of advanced non-small-cell lung cancer with docetaxel and gemcitabine: a multicenter phase II trial.

PURPOSE: To evaluate the tolerance and efficacy of the combination of docetaxel and gemcitabine in patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Fifty-one chemotherapy-naive patients with NSCLC were treated with gemcitabine 900 mg/m2 intravenously on days 1 and 8 and docetaxel 100 mg/m2 intravenously on day 8 with granulocyte colony-stimulating factor (150 microg/m2, subcutaneously) support from day 9 to day 15. Treatment was repeated every 3 weeks. RESULTS: The patients' median age was 64 years. The World Health Organization performance status was 0 to 1 in 39 patients and 2 in 12 patients. Fifteen patients (29%) had stage IIIB disease, and 36 (71%) had stage IV; histology was mainly squamous cell carcinoma (59%). A partial response was achieved in 19 patients (37.5%; 95% confidence interval, 24% to 50%); stable disease and progressive disease were each observed in 16 patients (31.4%). The median duration of response and the time to tumor progression were 5 and 6 months, respectively. The median survival was 13 months, and the actuarial 1-year survival was 50.7%. Grade 4 anemia and thrombocytopenia were rare (2%). Four patients (8%) developed grade 3 or 4 neutropenia, and all were complicated with fever; there was no treatment-related death. Grade 3 or 4 diarrhea occurred in three patients (6%), grade 2 or 3 neurotoxicity in four patients (8%), grade 2 or 3 asthenia in 10 patients (20%), and grade 2 or 3 edema in 10 patients (20%). CONCLUSION: The combination of docetaxel/gemcitabine is well tolerated, can be used for outpatients, and is active for the treatment of advanced NSCLC. This treatment merits further comparison with other cisplatin- or carboplatin-based combinations.     

Docetaxel and granulocyte colony-stimulating factor in patients with advanced non-small-cell lung cancer previously treated with platinum-based chemotherapy: a multicenter phase II trial

Purpose: To investigate the activity of docetaxel and granulocyte colony-stimulating factor support (G-CSF) in patients with advanced non-small-cell lung cancer (NSCLC) previously treated with cisplatin. Patients and methods: A total of 60 patients with locoregional and metastatic NSCLC who had relapsed or progressed after first-line treatment with cisplatin-based regimens were enrolled into the trial. Docetaxel at 100 mg/m² was given as a 1-h infusion with G-CSF (rhG-CSF given s.c. at 150 μg/m²) support from day 2 to day 8 every 3 weeks; all patients received premedication with corticosteroids. Results: In all, 1 (1.6%) and 14 (23.3%) patients achieved a complete response (CR) and a partial response (PR), respectively, for an overall response rate of 25% (95% CI 14.0–35.9%); stable disease (SD) and progressive disease (PD) were documented in 18 (30%) and 27 (45%) patients, respectively. The median duration of response was 20 weeks and the median time to tumor progression was 28 weeks. The median overall survival was 32 weeks and the 1-year survival rate was 23%. A total of 263 courses were given at a median of 3 cycles/patient. Grade 3 and 4 neutropenia occurred in 11 (18%) and 14 (23%) patients, respectively, with 18 (30%) patients requiring hospitalization for neutropenic fever; 1 patient died of sepsis. Grade 2 peripheral neuropathy occurred in 9 patients (15%) and grade 3 asthenia, in 4 (7%). Other toxicities were mild. Conclusions: Docetaxel has considerable single-agent activity in patients with NSCLC who have relapsed or progressed after first-line chemotherapy with cisplatin-based regimens. Received: 17 June 1998 / Accepted: 17 August 1998     

Docetaxel versus docetaxel/cisplatin in patients with advanced non-small-cell lung cancer: preliminary analysis of a multicenter, randomized phase III study

The purpose of this study was to compare the efficacy and safety profile of docetaxel versus the combination of docetaxel/cisplatin as frontline treatment of patients with advanced or metastatic non-small-cell lung cancer (NSCLC) in a multicenter, randomized, prospective phase III trial. Patients with unresectable stage IIIB or metastatic stage IV NSCLC who had previously undergone no chemotherapy were allocated to receive either docetaxel (100 mg/m2 in a 1-hour intravenous infusion; group A) or the combination of docetaxel (100 mg/m2 day 1) and cisplatin (80 mg/m2 day 2) after adequate hydration (group B). Appropriate premedication was given before docetaxel infusion. All patients in group B received granulocyte colony-stimulating factor (150 microg/m2 subcutaneously) support from days 3 to 9 after treatment. Response and toxicity were assessed by World Health Organization criteria. From March 1999 to November 2001, 302 patients were randomly assigned to receive docetaxel (group A, n = 146) or docetaxel/cisplatin (group B, n = 156). The overall response rate was significantly higher in the combination arm (18% vs. 36%; P < 0.001). However, the 2 groups did not differ in median duration of response, time to progression (TTP), median overall survival (OS), or 1-year survival rate. Drug combination was associated with higher toxicity than single-agent therapy. Both regimens had comparable activity in terms of TTP and OS in chemotherapy-naive patients with advanced NSCLC; however, single-agent therapy had a more favorable toxicity profile.     

A randomized,phase III multicenter trial of gemcitabine in combination with carboplatin or paclitaxel versus paclitaxel plus carboplatin in patients with advanced or metastatic non-small-cell lung cancer

BackgroundPaclitaxel–carboplatin is used as the standard regimen for patients with advanced or metastatic non-small-cell lung cancer (NSCLC). This trial was designed to compare gemcitabine + carboplatin or gemcitabine + paclitaxel to the standard regimen.Patients and methodsA total of 1135 chemonaive patients with stage IIIB or IV NSCLC were randomly allocated to receive gemcitabine 1000 mg/m² on days 1 and 8 plus carboplatin area under the concentration–time curve (AUC) 5.5 on day 1 (GC), gemcitabine 1000 mg/m² on days 1 and 8 plus paclitaxel 200 mg/m² on day 1 (GP), or paclitaxel 225 mg/m² plus carboplatin AUC 6.0 on day 1 (PC). Stratification was based on disease stage, baseline weight loss, and presence or absence of brain metastases. Cycles were repeated every 21 days for up to six cycles or disease progression.ResultsMedian survival (months) with GC was 7.9 compared with 8.5 for GP and 8.7 for PC. Response rates (RRs) were as follows: GC, 25.3%; GP, 32.1%; and PC, 29.8%. The GC arm was associated with a greater incidence of grade 3 or 4 hematologic events but a lower rate of neurotoxicity and alopecia when compared with GP and PC.ConclusionsNon-platinum and non-paclitaxel gemcitabine-containing doublets demonstrate similar overall survival and RR compared with the standard PC regimen. However, the treatment arms had distinct toxicity profiles.     

Chemotherapy for elderly patients with advanced non-small-cell lung cancer: the Multicenter Italian Lung Cancer in the Elderly Study (MILES) phase III randomized trial

BACKGROUND: Vinorelbine prolongs survival and improves quality of life in elderly patients with advanced non-small-cell lung cancer (NSCLC). Some studies have also suggested that gemcitabine is well tolerated and effective in such patients. We compared the effectiveness and toxicity of the combination of vinorelbine plus gemcitabine with those of each drug given alone in an open-label, randomized phase III trial in elderly patients with advanced NSCLC. METHODS: Patients aged 70 years and older, enrolled between December 1997 and November 2000, were randomly assigned to receive intravenous vinorelbine (30 mg/m(2) of body surface area), gemcitabine (1200 mg/m(2)), or vinorelbine (25 mg/m(2)) plus gemcitabine (1000 mg/m(2)). All treatments were delivered on days 1 and 8 every 3 weeks for a maximum of six cycles. The primary endpoint was survival. Survival curves were drawn using the Kaplan-Meier method and analyzed by the Mantel-Haenszel test. Secondary endpoints were quality of life and toxicity. RESULTS: Of 698 patients available for intention-to-treat analysis, 233 were assigned to receive vinorelbine, 233 to gemcitabine, and 232 to vinorelbine plus gemcitabine. Compared with each single drug, the combination treatment did not improve survival. The hazard ratio of death for patients receiving the combination treatment was 1.17 (95% confidence interval [CI] = 0.95 to 1.44) that of patients receiving vinorelbine and 1.06 (95% CI = 0.86 to 1.29) that of patients receiving gemcitabine. Although quality of life was similar across the three treatment arms, the combination treatment was more toxic than the two drugs given singly. CONCLUSION: The combination of vinorelbine plus gemcitabine is not more effective than single-agent vinorelbine or gemcitabine in the treatment of elderly patients with advanced NSCLC.     

Randomized clinical trial of adenosine 5'-triphosphate in patients with advanced non-small-cell lung cancer

BACKGROUND: Extracellular adenosine 5'-triphosphate (ATP) is involved in the regulation of a variety of biologic processes, including neurotransmission, muscle contraction, and liver glucose metabolism, via purinergic receptors. In nonrandomized studies involving patients with different tumor types including non-small-cell lung cancer (NSCLC), ATP infusion appeared to inhibit loss of weight and deterioration of quality of life (QOL) and performance status. We conducted a randomized clinical trial to evaluate the effects of ATP in patients with advanced NSCLC (stage IIIB or IV). METHODS: Fifty-eight patients were randomly assigned to receive either 10 intravenous 30-hour ATP infusions, with the infusions given at 2- to 4-week intervals, or no ATP. Outcome parameters were assessed every 4 weeks until 28 weeks. Between-group differences were tested for statistical significance by use of repeated-measures analysis, and reported P values are two-sided. RESULTS: Twenty-eight patients were allocated to receive ATP treatment and 30 received no ATP. Mean weight changes per 4-week period were -1.0 kg (95% confidence interval [CI] = -1.5 to -0.5) in the control group and 0.2 kg (95% CI = -0.2 to +0.6) in the ATP group (P =.002). Serum albumin concentration declined by -1.2 g/L (95% CI= -2.0 to -0.4) per 4 weeks in the control group but remained stable (0.0 g/L; 95% CI = -0.3 to +0.3) in the ATP group (P =.006). Elbow flexor muscle strength declined by -5.5% (95% CI = -9.6% to -1. 4%) per 4 weeks in the control group but remained stable (0.0%; 95% CI= -1.4% to +1.4%) in the ATP group (P =.01). A similar pattern was observed for knee extensor muscles (P =.02). The effects of ATP on body weight, muscle strength, and albumin concentration were especially marked in cachectic patients (P =.0002, P =.0001, and P =. 0001, respectively, for ATP versus no ATP). QOL score changes per 4-week period in the ATP group showed overall less deterioration than in the control group-physical scores (-0.2% versus -2.4%; P =. 0002); functional scores (+0.4% versus -5.5%; P =.02); psychologic scores (-0.7% versus -2.4%; P =.11); overall QOL score (+0.1% versus -3.5%; P =.0001). CONCLUSIONS: This randomized trial demonstrates that ATP has beneficial effects on weight, muscle strength, and QOL in patients with advanced NSCLC.     

Phase III randomized trial comparing three platinum-based doublets in advanced non-small-cell lung cancer.

PURPOSE: To evaluate whether two commonly used newer platinum-based regimens offer any advantage over vinorelbine-cisplatin (reference regimen) in response rate for patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Chemotherapy-naive patients were randomized to receive gemcitabine 1,250 mg/m(2) days 1 and 8 plus cisplatin 75 mg/m(2) day 2 every 21 days (GC arm), or paclitaxel 225 mg/m(2) (3-hour infusion) then carboplatin (area under the concentration-time curve of 6 mg/mL x min), both on day 1 every 21 days (PCb arm), or vinorelbine 25 mg/m(2)/wk for 12 weeks then every other week plus cisplatin 100 mg/m(2) day 1 every 28 days (VC arm). RESULTS: Six hundred twelve patients were randomized to treatment (205 GC, 204 PCb, and 203 VC). Overall response rates for the GC (30%) and PCb (32%) arms were not significantly different from that of the VC arm (30%). There were no differences in overall survival, time to disease progression, or time to treatment failure. Median survival for the GC, PCb, and VC groups was 9.8, 9.9, and 9.5 months, respectively. Neutropenia was significantly higher on the VC arm (GC 17% or PCb 35% v VC 43% of cycles, P <.001), as was thrombocytopenia on the GC arm (GC 16% v VC 0.1% of cycles, P <.001). Alopecia and peripheral neurotoxicity were most common on the PCb arm, as was nausea/vomiting on the VC arm (P <.05). CONCLUSION: Efficacy end points were not significantly different between experimental and reference arms, although toxicities showed differences. These findings suggest that chemotherapy in NSCLC has reached a therapeutic plateau.     

Liposomal cisplatin combined with paclitaxel versus cisplatin and paclitaxel in non-small-cell lung cancer: a randomized phase III multicenter trial

BackgroundLiposomal cisplatin is a new formulation developed to reduce the systemic toxicity of cisplatin while simultaneously improving the targeting of the drug to the primary tumor and to metastases by increasing circulation time in the body fluids and tissues. The primary objectives were to determine nephrotoxicity, gastrointestinal side-effects, peripheral neuropathy and hematological toxicity and secondary objectives were to determine the response rate, time to tumor progression (TTP) and survival.Patients and methodsTwo hundred and thirty-six chemotherapy-naive patients with inoperable non-small-cell lung cancer were randomly allocated to receive either 200 mg/m² of liposomal cisplatin and 135 mg/m² paclitaxel (arm A) or 75 mg/m² cisplatin and 135 mg/m² paclitaxel (arm B), once every 2 weeks on an outpatient basis. Two hundred and twenty-nine patients were assessable for toxicity, response rate and survival. Nine treatment cycles were planned.ResultsArm A patients showed statistically significant lower nephrotoxicity, grade 3 and 4 leucopenia, grade 2 and 3 neuropathy, nausea, vomiting and fatigue. There was no significant difference in median and overall survival and TTP between the two arms; median survival was 9 and 10 months in arms A and B, respectively, and TTP was 6.5 and 6 months in arms A and B, respectively.ConclusionsLiposomal cisplatin in combination with paclitaxel has been shown to be much less toxic than the original cisplatin combined with paclitaxel. Nephrotoxicity in particular was negligible after liposomal cisplatin administration. TTP and survival were similar in both treatment arms.