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  铂类为基础的化疗方案成为NSCLC姑息化疗标准方案始于1988年这篇文章,以后多次临床试验和META分析证实铂类在NSCLC不可动摇的地位(不好意思,这盘全文我没弄到)
Chemotherapy can prolong survival in patients with advanced non-small- cell lung cancer--report of a Canadian multicenter randomized trial
E Rapp, JL Pater, A Willan, Y Cormier, N Murray, WK Evans, DI Hodson, DA Clark, R Feld and AM Arnold
National Cancer Institute of Canada, Queen's University, Kingston, Ontario.

The survival benefit of combination chemotherapy to patients with advanced non-small-cell carcinoma of the lung (NSCLC) is controversial. To study this question, the National Cancer Institute of Canada (NCIC) Clinical Trials Group conducted a prospective randomized trial comparing best supportive care (BSC) to two chemotherapy regimens, vindesine and cisplatin (VP), and cyclophosphamide, doxorubicin, and cisplatin (CAP). Between February 1983 and January 1986, 23 centers across Canada entered 251 patients on study. Eighteen centers participated in the three-arm schema (150 patients); centers choosing not to participate in a study with a no-chemotherapy arm followed a two- arm schema comparing VP with CAP (101 additional patients). Altogether, 233 patients were eligible. Patients had measurable or evaluable disease, with either distant metastases (82.5%) or bulky limited disease considered inoperable or unsuitable for radical radiotherapy. The treatment groups were comparable in terms of age, sex, performance status, histology, disease extent, and weight loss. The overall response rates (complete response [CR] plus partial response [PR]) on the chemotherapy arms were CAP, 15.3%, and VP, 25.3% (P = .06). Patients on the three-arm portion of the trial had a median survival of 32.6 weeks when treated with VP, 24.7 weeks with CAP, and 17 weeks with BSC. The significance of the differences in survival, adjusted for prognostic factors, is as follows: chemotherapy v BSC, P = .02; VP v BSC, P = .01; and CAP v BSC, P = .05. Toxicity on the chemotherapy arms was significant, with leukopenia of severe or greater degree occurring in 37.8% (CAP) and 40.0% (VP), severe vomiting in 12.2% (CAP) and 23.3% (VP), and severe neurotoxicity in 15.6% (VP).

1995年BMJ发表的这篇META分析也是很有影响力的，探讨了辅助化疗，姑息化疗的地位，这个研究的结论是：含有铂类的化疗方案能提高病人的生存率，术后加上化疗与单独手术比较，减少了死亡危险13％，5年生存率提高5％；放射治疗联合化学治疗比起单独的放射治疗，死亡危险减少了13％，2年生存率提高4％；支持疗法联合化学治疗，比起单独的支持疗法，死亡危险减少了27％，1年生存率提高10％。
Chemotherapy in non-small cell lung cancer: a meta-analysis using updated data on individual patients from 52 randomised clinical trials. Non-small Cell Lung Cancer Collaborative Group

Objective: To evaluate the effect of cytotoxic chemotherapy on survival in patients with non-small cell lung cancer.
Design: Meta-analysis using updated data on individual patients from all available randomised trials, both published and unpublished.
Subjects: 9387 patients (7151 deaths) from 52 randomised clinical trials.
Main outcome measure: Survival.
Results: The results for modern regimens containing cisplatin favoured chemotherapy in all comparisons and reached conventional levels of significance when used with radical radiotherapy and with supportive care. Trials comparing surgery with surgery plus chemotherapy gave a hazard ratio of 0.87 (13% reduction in the risk of death, equivalent to an absolute benefit of 5% at five years). Trials comparing radical radiotherapy with radical radiotherapy plus chemotherapy gave a hazard ratio of 0.87 (13% reduction in the risk of death; absolute benefit of 4% at two years), and trials comparing supportive care with supportive care plus chemotherapy 0.73 (27% reduction in the risk of death; 10% improvement in survival at one year). The essential drugs needed to achieve these effects were not identified. No difference in the si
Conclusion: At the outset of this meta-analysis there was considerable pessimism about the role of chemotherapy in non-small cell lung cancer. These results offer hope of progress and suggest that chemotherapy may have a role in treating this disease
全文链接：http://www.bmj.com/cgi/content/full/311/7010/899

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2003年之前,NSCLC辅助化疗是没有定论的,很多临床试验结果不相一致,International Adjuvant Lung Trial (IALT)将1867名接受根治性手术的NSCLC患者随机分入辅助化疗组和观察组,证实了铂类为基础的双药方案可以使患者获益.DFS绝对值提高5%,OS提高4%.
至此,辅助化疗成为标准

background
On the basis of a previous meta-analysis, the International Adjuvant Lung Cancer Trial
was designed to evaluate the effect of cisplatin-based adjuvant chemotherapy on survival
after complete resection of non–small-cell lung cancer.
methods
We randomly assigned patients either to three or four cycles of cisplatin-based chemotherapy
or to observation. Before randomization, each center determined the pathological
stages to include, its policy for chemotherapy (the dose of cisplatin and the drug to
be combined with cisplatin), and its postoperative radiotherapy policy. The main end
point was overall survival.
results
A total of 1867 patients underwent randomization; 36.5 percent had pathological stage
I disease, 24.2 percent stage II, and 39.3 percent stage III. The drug allocated with cisplatin
was etoposide in 56.5 percent of patients, vinorelbine in 26.8 percent, vinblastine in
11.0 percent, and vindesine in 5.8 percent. Of the 932 patients assigned to chemotherapy,
73.8 percent received at least 240 mg of cisplatin per square meter of body-surface
area. The median duration of follow-up was 56 months. Patients assigned to chemotherapy
had a significantly higher survival rate than those assigned to observation (44.5 percent
vs. 40.4 percent at five years [469 deaths vs. 504]; hazard ratio for death, 0.86; 95
percent confidence interval, 0.76 to 0.98; P<0.03). Patients assigned to chemotherapy
also had a significantly higher disease-free survival rate than those assigned to observation
(39.4 percent vs. 34.3 percent at five years [518 events vs. 577]; hazard ratio, 0.83;
95 percent confidence interval, 0.74 to 0.94; P<0.003). There were no significant interactions
with prespecified factors. Seven patients (0.8 percent) died of chemotherapyinduced
toxic effects.
conclusions
Cisplatin-based adjuvant chemotherapy improves survival among patients with completely
resected non–small-cell lung cancer.

Cisplatin-Based Adjuvant Chemotherapy.pdf (130.04k)

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2003年之前,NSCLC辅助化疗是没有定论的,很多临床试验结果不相一致,International Adjuvant Lung Trial (IALT)将1867名接受根治性手术的NSCLC患者随机分入辅助化疗组和观察组,证实了铂类为基础的双药方案可以使患者获益.DFS绝对值提高5%,OS提高4%.
至此,辅助化疗成为标准

background
On the basis of a previous meta-analysis, the International Adjuvant Lung Cancer Trial
was designed to evaluate the effect of cisplatin-based adjuvant chemotherapy on survival
after complete resection of non–small-cell lung cancer.
methods
We randomly assigned patients either to three or four cycles of cisplatin-based chemotherapy
or to observation. Before randomization, each center determined the pathological
stages to include, its policy for chemotherapy (the dose of cisplatin and the drug to
be combined with cisplatin), and its postoperative radiotherapy policy. The main end
point was overall survival.
results
A total of 1867 patients underwent randomization; 36.5 percent had pathological stage
I disease, 24.2 percent stage II, and 39.3 percent stage III. The drug allocated with cisplatin
was etoposide in 56.5 percent of patients, vinorelbine in 26.8 percent, vinblastine in
11.0 percent, and vindesine in 5.8 percent. Of the 932 patients assigned to chemotherapy,
73.8 percent received at least 240 mg of cisplatin per square meter of body-surface
area. The median duration of follow-up was 56 months. Patients assigned to chemotherapy
had a significantly higher survival rate than those assigned to observation (44.5 percent
vs. 40.4 percent at five years [469 deaths vs. 504]; hazard ratio for death, 0.86; 95
percent confidence interval, 0.76 to 0.98; P<0.03). Patients assigned to chemotherapy
also had a significantly higher disease-free survival rate than those assigned to observation
(39.4 percent vs. 34.3 percent at five years [518 events vs. 577]; hazard ratio, 0.83;
95 percent confidence interval, 0.74 to 0.94; P<0.003). There were no significant interactions
with prespecified factors. Seven patients (0.8 percent) died of chemotherapyinduced
toxic effects.
conclusions
Cisplatin-based adjuvant chemotherapy improves survival among patients with completely
resected non–small-cell lung cancer.

Cisplatin-Based Adjuvant Chemotherapy.pdf (130.04k)

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三期B，四期肺癌（NSLC）治疗

临床随机对照试验：ECOG1594，SWOG9509，TAX326

ECOG 1594 was a large randomized trial in which 1105 patients with stage IIIB or IV NSCLC were randomized to receive 1 of 4 platinum-based regimens: paclitaxel plus cisplatin, gemcitabine plus cisplatin, docetaxel plus cisplatin, or paclitaxel plus carboplatin. There was no significant difference in the 4 groups with respect to response rate (15% - 21%), median survival (7.4 ?C 8.2 months), and 1-year survival (31% - 36%). However, there was no accounting in this trial for the possible impact of second-line therapy patients may have received after removal from this study. There was a slight increase in time-to-progression for the gemcitabine/cisplatin arm; however, this modest difference may be explained by the fact that this arm was the only one that used an every-4-week cycle. The incidence of thrombocytopenia and anemia were higher in the gemcitabine/cisplatin arm. With regard to non-hematologic toxicities, nausea and vomiting occurred with least frequency in the paclitaxel/carboplatin arm, and there was a slightly higher incidence of renal toxicity in the gemcitabine/cisplatin arm. However, the incidence of other toxicities was equivalent across the four treatment groups. The investigators concluded from ECOG 1594 that the four regimens studied in this trial showed no significant differences in survival or response rate, and relatively minor differences in toxicities, so that any of these regimens would be equally acceptable treatment options for advanced NSCLC. One caveat with this trial, as with any study of this kind, is that it does not take into account the possible impact of second-line therapy.

TAX 326 was another large randomized trial in which 1218 patients with stage IIIB or IV NSCLC were randomized to receive either docetaxel + cisplatin (DC) or docetaxel + carboplatin (DCb) versus a reference regimen of vinorelbine + cisplatin (VC). In the first comparison of DC versus VC, the overall survival in the DC arm was greater than the VC control (p = 0.044). The survival curves separate at about 4 months, and then remain non-overlapping throughout the follow-up period. Median survival was 11.3 months, 1-year survival was 46%, and 2-year survival was 21%, compared with 10.1 months, 41%, and 14% in the control group. In support of the survival benefit is the fact that the response rate was also in favor of the DC arm: 32% versus 25% in the VC control (p = 0.029). In the second comparison of DCb versus VC, the overall, median, and 1-year survivals between these 2 groups were equivalent, as were the response rates of 24%-25%.

One unique aspect of this trial was the demonstrated impact on quality of life (QoL) for patients treated in the docetaxel arms. QoL was evaluated prospectively using the LCSS and EuroQoL instruments. In the first comparison of DC versus VC, the changes in global QoL were consistently positive in the DC group, while the changes in the VC group were consistently negative (p = 0.016). Similar improvements were seen in other clinical benefit parameters. For example, there was a greater improvement in the pain score and in weight loss for the patients in the DC group compared to VC (p = 0.033 for pain; p < 0.001 for weight loss), and a consistent trend favoring DC compared with VC was also noted for improvement in performance status. Similar improvements in QoL parameters were also noted in the second comparison of DCb versus VC. Changes in global QoL, pain, weight loss, and performance status consistently favored the patients in the DCb arm.

The incidence of severe anemia and severe nausea/vomiting was significantly higher with VC than either of the docetaxel arms. However, other toxicity was comparable between the 3 groups.

In conclusion, the response rate and overall survival with docetaxel + cisplatin were greater than that seen with VC. And the response rate and survival with docetaxel + carboplatin were equivalent to the control regimen. Patients in the control group had a higher incidence of anemia, nausea, and vomiting. And, finally, significant improvement in several quality of life parameters were noted to both docetaxel groups as compared with the control regimen.

In support of TAX 326 is a phase III Japanese trial reported by Kunitoh. In this trial, 302 patients with stage IV NSCLC were randomized to receive docetaxel + cisplatin (DC) versus their reference regimen of vindesine + cisplatin (VdC). There was a significantly higher response rate in the patients who received DC: 37% versus 21% with VdC, as well as an improvement in overall and median survival favoring the DC arm.

In summary, the ECOG 1594 trial showed comparable activity and toxicity between four commonly used platinum-based chemotherapy regimens. And two additional phase III trials comparing docetaxel + platinum combinations versus another platinum-containing reference regimen have shown improvement in response rate and survival with cisplatin plus docetaxel. Furthermore, one of those trials (TAX 326) showed significant improvement in several quality of life parameters for patients who received docetaxel plus either cisplatin or carboplatin compared with the control regimen. These studies support the emerging role for docetaxel plus platinum combinations in the first-line treatment of advanced NSCLC

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topotecan（托泊替康）是一种半合成水溶性喜树碱衍生物，最先作为以Topo -Ⅰ为目标的药物进入癌症临床试验。在治疗肺癌上显示出较高的体内活性。

PURPOSE: A phase I and pharmacologic study was undertaken to determine the maximum-tolerated dose (MTD), describe the principal toxicities, and characterize the pharmacologic behavior of topotecan, which is a semisynthetic analog of camptothecin with broad preclinical antitumor activity and the first topoisomerase I-targeting agent to enter clinical development in the United States since studies of sodium camptothecin over 2 decades ago. PATIENTS AND METHODS: Thirty-minute infusions of topotecan were administered daily for 5 consecutive days every 3 weeks to patients with advanced solid malignancies at doses ranging from 0.5 to 2.5 mg/m2/d. RESULTS: At doses of 1.5 and 2.0 mg/m2, grade 3 and 4 neutropenia occurred in most courses; however, neutropenia was brief and rarely associated with fevers or treatment delays. Neutropenia was more severe in patients with extensive prior treatment than in minimally pretreated patients, but these differences were not substantial. At 2.5 mg/m2, topotecan induced profound and prolonged neutropenia that was frequently associated with fever and treatment delays in minimally pretreated patients. Topotecan also induced mild depressions in the hematocrit level in the majority of courses; however, precipitous drops requiring transfusional therapy occurred in 14% of courses and suggested a drug-induced hemolytic effect. Unlike sodium camptothecin, hemorrhagic cystitis was not observed. Thrombocytopenia, skin rash, diarrhea, and vomiting occurred infrequently and were modest in severity. Responses were observed in non-small-cell lung carcinoma and platinum-refractory ovarian carcinoma. Drug disposition in plasma was described by a biexponential model, with renal elimination accounting for 38.7% of drug disposition. Topotecan was rapidly hydrolyzed in vivo to a less active, open-ring form. CONCLUSIONS: Neutropenia is the dose-limiting toxicity, and 1.5 mg/m2 is the recommended starting dose of topotecan for both minimally and heavily pretreated patients in future phase II trials, with escalation to 2.0 mg/m2 if treatment is well tolerated. Non-small-cell lung and platinum-refractory ovarian carcinomas should be among those evaluated in phase II trials of topotecan.

喜树碱衍生物单用药的研究日趋成熟，进一步考虑将它们与其他抗癌药物以及生化反应调节剂等联用，克服药物毒性反应，并提高疗效，将使喜树碱衍生物的应用更为广泛，继续成为临床抗癌治疗的理想药物。

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1992年12月29日，美国FDA正式批准紫杉醇作为治疗肺癌的化疗药上市。
这是最早的一篇关于紫杉醇治疗非小细胞肺癌和小细胞肺癌的临床研究文章。（我没有全文，不好意思）

Semin Oncol. 1993 Aug;20(4 Suppl 3):46-9.

Overview of paclitaxel (Taxol) in advanced lung cancer.

Johns Hopkins Oncology Center, Baltimore, MD 21287-8936.

Paclitaxel (TAXOL), a novel diterpene plant product isolated from the western yew Taxus brevifolia, is an active agent in the treatment of lung cancer. In two studies, the drug produced 21% and 24% objective response rates among patients with non-small cell lung cancer. A response rate of 34% was reported in a single trial involving patients with extensive-stage small cell lung cancer. Additional trials are needed to evaluate single-agent paclitaxel in the treatment of small cell lung cancer. Studies also are planned to measure the effect of paclitaxel as a radiosensitizer and in combination regimens with other active agents for the treatment of lung cancer.

紫杉醇具有独特的抗肿瘤作用，它能与微管蛋白结合，形成稳定的稳管束，并使之被解聚，将癌细胞停止在G2晚期，抑制细胞复制，阻止癌细胞增殖。是目前唯一能控制癌细胞生长的植物药，也是晚期癌症最后一道防线。

但是因为其昂贵的价格，以及越来越有限的来源使其应用受到了一定限制。

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奠定紫杉醇在晚期NSCLC化疗中地位的一篇文献
Comparison of Survival and Quality of Life in Advanced Non–Small-Cell Lung Cancer Patients Treated With Two Dose Levels of Paclitaxel Combined With Cisplatin Versus Etoposide With Cisplatin: Results of an Eastern Cooperative Oncology Group Trial

Purpose: Treatment with cisplatin-based chemotherapy provides a modest survival advantage over supportive care alone in advanced non–small-cell lung cancer (NSCLC). To determine whether a new agent, paclitaxel, would further improve survival in NSCLC, the Eastern Cooperative Oncology Group conducted a randomized trial comparing paclitaxel plus cisplatin to a standard chemotherapy regimen consisting of cisplatin and etoposide.
Patients and Methods: The study was carried out by a multi-institutional cooperative group in chemotherapy- naive stage IIIB to IV NSCLC patients randomized to receive paclitaxel plus cisplatin or etoposide plus cisplatin. Paclitaxel was administered at two different dose levels (135 mg/m2 and 250 mg/m2), and etoposide was given at a dose of 100 mg/m2 daily on days 1 to 3. Each regimen was repeated every 21 days and each
included cisplatin (75 mg/m2).
Results: The characteristics of the 599 patients were well-balanced across the three treatment groups. Superior survival was observed with the combined paclitaxel regimens (median survival time, 9.9 months; 1-year survival rate, 38.9%) compared with etoposide plus cisplatin (median survival time, 7.6 months; 1-year survival rate, 31.8%; P 5 .048). Comparing survival for the two dose levels of paclitaxel revealed no significant
difference. The median survival duration for the stage IIIB subgroup was 7.9 months for etoposide plus cisplatin patients versus 13.1 months for all paclitaxel patients
(P 5.152). For the stage IV subgroup, the median survival time for etoposide plus cisplatin was 7.6 months compared with 8.9 months for paclitaxel (P 5 .246). With the exceptions of increased granulocytopenia on the low-dose paclitaxel regimen and increased myalgias, neurotoxicity, and, possibly, increased treatment-related cardiac events with high-dose paclitaxel, toxicity was similar across all three arms. Quality of life (QOL) declined significantly over the 6 months. However, QOL scores were not significantly different among the regimens.
Conclusion: As a result of these observations, paclitaxel (135 mg/m2) combined with cisplatin has replaced etoposide plus cisplatin as the reference regimen in our recently completed phase III trial.
J Clin Oncol 18:623-631.

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谈到晚期NSCLC化疗，不可不谈ECOG1594
COMPARISON OF FOUR CHEMOTHERAPY REGIMENS FOR ADVANCED
NON–SMALL-CELL LUNG CANCER

ABSTRACT
Background：We conducted a randomized study to determine whether any of three chemotherapy regimens was superior to cisplatin and paclitaxel in patients
with advanced non–small-cell lung cancer. Methods
A total of 1207 patients with advanced non–small-cell lung cancer were randomly assigned to a reference regimen of cisplatin and paclitaxel or to one of three experimental regimens: cisplatin and gemcitabine, cisplatin and docetaxel, or carboplatin and paclitaxel.
Results The response rate for all 1155 eligible patients was 19 percent, with a median survival of 7.9 months (95 percent confidence interval, 7.3 to 8.5), a 1-year survival rate of 33 percent (95 percent confidence interval, 30 to 36 percent), and a 2-year survival rate of 11 percent (95 percent confidence interval, 8 to 12 percent). The response rate and survival did not differ significantly between patients assigned to receive cisplatin and paclitaxel and those assigned to receive any of the three experimental regimens. Treatment with cisplatin and gemcitabine was associated with a significantly longer time to the progression of disease than was treatment with cisplatin and paclitaxel
but was more likely to cause grade 3, 4, or 5 renal toxicity (in 9 percent of patients, vs. 3 percent of those treated with cisplatin plus paclitaxel). Patients with a performance status of 2 had a significantly lower rate of survival than did those with a performance status of 0 or 1.
Conclusions None of four chemotherapy regimens offered a significant advantage over the others in the treatment of advanced non–small-cell lung cancer.
(N Engl J Med 2002;346:92-8.)
Copyright

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SWOG9509
泰素＋卡铂与NVB+顺铂比较的比较
在生存率，有效率均无显著差异，但是泰素＋卡铂有毒副作用较轻、生活质量较好的优势。

Randomized Phase III Trial of Paclitaxel Plus Carboplatin Versus Vinorelbine Plus Cisplatin in the Treatment of Patients With Advanced Non–Small-Cell Lung Cancer: A Southwest Oncology Group Trial
By Karen Kelly, John Crowley, Paul A. Bunn, Jr, Cary A. Presant, Patra K. Grevstad, Carol M. Moinpour, Scott D. Ramsey, Antoinette J. Wozniak, Geoffrey R. Weiss, Dennis F. Moore, Valerie K. Israel, Robert B. Livingston, David R. Gandara
From the University of Colorado, Denver, CO; Southwest Oncology Group Statistical Center, Fred Hutchinson Cancer Research Center, Swedish Medical Center, and University of Washington, Seattle, WA; St Vincent Medical Center, Los Angeles Oncology Institute, and University of Southern California School of Medicine, Los Angeles; University of California Davis, Sacramento, CA; Wayne State University Medical Center, Detroit, MI; University of Texas Health Science Center San Antonio, San Antonio, TX; and Wichita Community Clinical Oncology Program, Wichita, KS.

Address reprint requests to Southwest Oncology Group (SWOG-9509), Operations Office, 14980 Omicron Dr, San Antonio, TX 78245-3217.

PURPOSE: This randomized trial was designed to determine whether paclitaxel plus carboplatin (PC) offered a survival advantage over vinorelbine plus cisplatin (VC) for patients with advanced non–small-cell lung cancer. Secondary objectives were to compare toxicity, tolerability, quality of life (QOL), and resource utilization.

PATIENTS AND METHODS: Two hundred two patients received VC (vinorelbine 25 mg/m2/wk and cisplatin 100 mg/m2/d, day 1 every 28 days) and 206 patients received PC (paclitaxel 225 mg/m2 over 3 hours with carboplatin area under the curve of 6, day 1 every 21 days). Patients completed QOL questionnaires at baseline, 13 weeks, and 25 weeks. Resource utilization forms were completed at five time points through 24 months.

RESULTS: Patient characteristics were similar between the groups. The objective response rate was 28% in the VC arm and 25% in the PC arm. Median survival was 8 months in both arms, with 1-year survival rates of 36% and 38%, respectively. Grade 3 and 4 leukopenia (P = .002) and neutropenia (P = .008) occurred more frequently on the VC arm. Grade 3 nausea and vomiting were higher on the VC arm (P = .001, P = .007), and grade 3 peripheral neuropathy was higher on the PC arm (P < .001). More patients on the VC arm discontinued therapy because of toxicity (P = .001). No difference in QOL was observed. Overall costs on the PC arm were higher than on the VC arm because of drug costs.

CONCLUSION: PC is equally efficacious as VC for the treatment of advanced non–small-cell lung cancer. PC is less toxic and better tolerated but more expensive than VC. New treatment strategies should be pursued.

Phase III Trial of Paclitaxel Plus Carboplatin.pdf (144.29k)

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TAX326
Randomized, Multinational, Phase III Study of Docetaxel Plus Platinum Combinations Versus Vinorelbine Plus Cisplatin for Advanced Non–Small-Cell Lung Cancer: The TAX 326 Study Group
Frank Fossella, Jose R. Pereira, Joachim von Pawel, Anna Pluzanska, Vera Gorbounova, Eckhard Kaukel, Karin V. Mattson, Rodryg Ramlau, Aleksandra Szczsna, Panagiotis Fidias, Michael Millward, Chandra P. Belani

From the M.D. Anderson Cancer Center, Houston, TX; Instituto do C鈔cer Arnaldo Vieira de Carvalho, Sao Paulo, Brazil; Asklepios Fachkliniken München-Gauting, Gauting, Germany; M. Kopernik Memorial Hospital, Lodz, Poland; Cancer Research Center RAMS, Moscow, Russia; AK-Hamburg-Harbug, Hamburg, Germany; Helsinki University Central Hospital, Helsinki, Finland; Regional Lung Diseases Center, Pozna; Regional Lung Diseases Hospital, Otwock, Poland; Massachusetts General Hospital, Boston, MA; Sydney Cancer Centre, Camperdown, Australia; University of Pittsburgh Cancer Institute, Pittsburgh, PA.

Address reprint requests to Chandra P. Belani, MD, Division of Medical Oncology, University of Pittsburgh Cancer Institute, University of Pittsburgh Medical Center Cancer Pavilion, 5150 Center Ave, Suite 570, Pittsburgh, PA 15232; email: belanicp@msx.upmc.edu.

Purpose: To investigate whether docetaxel plus platinum regimens improve survival and affect quality of life (QoL) in advanced non–small-cell lung cancer (NSCLC) compared with vinorelbine plus cisplatin as first-line chemotherapy.

Patients and Methods: Patients (n = 1,218) with stage IIIB to IV NSCLC were randomly assigned to receive docetaxel 75 mg/m2 and cisplatin 75 mg/m2 every 3 weeks (DC); docetaxel 75 mg/m2 and carboplatin area under the curve of 6 mg/mL • min every 3 weeks (DCb); or vinorelbine 25 mg/m2/wk and cisplatin 100 mg/m2 every 4 weeks (VC).

Results: Patients treated with DC had a median survival of 11.3 v 10.1 months for VC-treated patients (P = .044; hazard ratio, 1.183 [97.2% confidence interval, 0.989 to 1.416]). The 2-year survival rate was 21% for DC-treated patients and 14% for VC-treated patients. Overall response rate was 31.6% for DC-treated patients v 24.5% for VC-treated patients (P = .029). Median survival (9.4 v 9.9 months [for VC]; P = .657; hazard ratio, 1.048 [97.2 confidence interval, 0.877 to 1.253]) and response (23.9%) with DCb were similar to those results for VC. Neutropenia, thrombocytopenia, infection, and febrile neutropenia were similar with all three regimens. Grade 3 to 4 anemia, nausea, and vomiting were more common (P < .01) with VC than with DC or DCb. Patients treated with either docetaxel regimen had consistently improved QoL compared with VC-treated patients, who experienced deterioration in QoL.

Conclusion: DC resulted in a more favorable overall response and survival rate than VC. Both DC and DCb were better tolerated and provided patients with consistently improved QoL compared with VC. These findings demonstrate that a docetaxel plus platinum combination is an effective treatment option with a favorable therapeutic index for first-line treatment of advanced or metastatic NSCLC.
1218位IIIB期或IV期的NSCLC病人被随机分组到泰索帝＋顺铂组（DC）或泰索帝＋卡铂组(DCb)及诺维本＋顺铂（VC）对照组。在DC对VC的比较中，DC组的总生存>VC组（p=0.044）。生活质量的改善也是有利于泰素帝组。

ltinational, Phase III Study of Docetaxel Plus.pdf (258.16k)

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顺铂还是卡铂？
这篇文章给出的观点是目前大多数人认同的
顺铂疗效稍优于卡铂
Meta-Analysis of Randomized Clinical Trials Comparing Cisplatin to Carboplatin in Patients With Advanced Non–Small-Cell Lung Cancer
Katsuyuki Hotta, Keitaro Matsuo, Hiroshi Ueoka, Katsuyuki Kiura, Masahiro Tabata, Mitsune Tanimoto
From the Department of Medicine II, Okayama University Medical School, Okayama; Department of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan.

Address reprint requests to Katsuyuki Hotta, MD, Department of Medicine II, Okayama University Medical School, 2-5-1 Shikata-cho, Okayama 700-8558, Japan; e-mail: khotta@md.okayama-u.ac.jp

PURPOSE: It remains undetermined whether cisplatin and carboplatin are equally effective for advanced non–small-cell lung cancer (NSCLC). We therefore did a meta-analysis of trials that compared cisplatin-based chemotherapy with carboplatin-based chemotherapy.

METHODS: We performed a literature search to identify trials that had investigated the substitution of carboplatin for cisplatin in the treatment of advanced NSCLC. We evaluated these trials for inclusion, rated methodologic quality, and abstracted relevant data.

RESULTS: Of 1,191 reports, eight trials (2,948 patients) were identified, five of which investigated drug regimens containing platinum plus a new agent. Cisplatin-based chemotherapy produced a higher response rate, but the survival advantage was not significant (hazard ratio = 1.050; 95% CI, 0.907 to 1.216; P = .515). Subgroup analysis revealed that combination chemotherapy consisting of cisplatin plus a new agent yields 11% longer survival than carboplatin plus the same new agent (hazard ratio = 1.106; 95% CI, 1.005 to 1.218; P = .039). Patients on cisplatin-based chemotherapy frequently developed nausea and vomiting; thrombocytopenia was more frequent during carboplatin-based chemotherapy. No significant difference in treatment-related mortality was observed.

CONCLUSION: We found that combination chemotherapy consisting of cisplatin plus a new agent yields a substantial survival advantage compared with carboplatin plus a new agent in patients with advanced NSCLC, although we failed to find any survival difference in an analysis that included both new and old agents. The strength of our conclusion is limited because we used abstracted data, and careful interpretation is thus required. Nevertheless, our results raise a critical point that needs to be evaluated in future studies.

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