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Phase III Randomized Trial Comparing Three Platinum-Based Doublets in Advanced Non–Small-Cell Lung Cancer

From the Department of Clinical and Biological Sciences, University of Torino, Turin; Division of Pneumo-Oncology V, C. Forlanini Hospital, Division of Medical Oncology B, Regina Elena Institute, and Division of Medical Oncology A, Regina Elena Institute, Rome; Division of Medical Oncology, Bellaria Hospital, Bologna; Division of Medical Oncology B, National Cancer Institute "G. Pascale" and Department of Endocrinology and Molecular and Clinical Oncology, Federico II University, Naples; Division of Medical Oncology, S. Chiara Hospital, Pisa; Division of Medical Oncology, S. Maria Hospital, Reggio Emilia; Division of Medical Oncology, S. Maria delle Croci Hospital, Ravenna; Division of Medical Oncology, S. Luigi and S. Curro Hospital, Catania; Department of Medical Oncology, University of Messina, Messina; Division of Medical Oncology, S. Giuseppe Hospital and Division of Medical Oncology, L. Sacco Hospital, Milan; Division of Medical Oncology, S. Maria Hospital, Terni; and Division of Medical Oncology, Policlinico Hospital, Perugia, Italy.

Address reprint requests to Giorgio V. Scagliotti, MD, University of Turin, Department of Clinical and Biological Sciences, Azienda Ospedaliera S Luigi, Regione Gonzole 10, 10043 Orbassano, Torino, Italy; email: scagliotti{at}ihnet.it

	ABSTRACT

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION REFERENCES

 
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/m² days 1 and 8 plus cisplatin 75 mg/m² day 2 every 21 days (GC arm), or paclitaxel 225 mg/m² (3-hour infusion) then carboplatin (area under the concentration-time curve of 6 mg/mL·min), both on day 1 every 21 days (PCb arm), or vinorelbine 25 mg/m²/wk for 12 weeks then every other week plus cisplatin 100 mg/m² 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.

	INTRODUCTION

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CISPLATIN-BASED combination therapy is currently considered the most active treatment option for patients with locally advanced or metastatic non–small-cell lung cancer (NSCLC).^1-3 The 1990s heralded the arrival of novel active drugs (gemcitabine, vinorelbine, taxanes, and topoisomerase I inhibitors) that, when combined with platinum compounds in the phase II setting, produced response and 1-year survival rates in excess of 50%.⁴ Four randomized clinical trials have definitively proven the superiority of different cisplatin-based doublets, including some of these newer agents, over cisplatin alone in terms of overall response rate and time to progressive disease^5-8 and, in three of the trials, median survival time.^5-7 Another group of randomized clinical trials compared newer doublets to older regimens (eg, cisplatin/epipodophyllotoxins, mitomycin/ifosfamide/cisplatin, or cisplatin/vindesine).^9-14 In most of these studies, the newer doublets produced a significant increase in objective response rate that did not always translate into an improvement in time to progressive disease or overall survival.

Among the newer doublets, gemcitabine/cisplatin (GC) and paclitaxel/carboplatin (PCb) are now commonly used in clinical practice. Consequently, the Italian Lung Cancer Project, including 31 Italian institutions, conducted a randomized study in chemotherapy-naive patients with advanced, recurrent, and/or metastatic NSCLC in which the primary end point of overall response rate was compared between the two experimental arms, GC and PCb, and the reference arm, vinorelbine/cisplatin (VC).

Because of increased interest in the patient’s perception of disease symptoms, treatment side effects, and their functional significance, we also assessed quality of life (QoL) with a lung cancer–specific instrument, the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30-LC13.¹⁵

	PATIENTS AND METHODS

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION REFERENCES

 
Patient Selection
Patients eligible for the study must have had locally advanced (stage IIIB with either pleural effusion or N3 supraclavicular nodal disease), recurrent, and/or metastatic (stage IV) NSCLC. The neoplastic disease must have been clinically assessable, as defined by objective imaging studies consistent with and supported by a pathologic (histologic or cytologic) diagnosis of NSCLC. The presence of at least one unidimensional measurable disease was mandatory and bidimensionally measurable disease was preferable. Although patients were required to be chemotherapy or immunotherapy naive, radiation therapy was permitted if concluded at least 4 weeks before entering the study (provided the irradiated site was not the only site of measurable disease), and prior surgery was allowed if the patient met all the other criteria specified. Patients were to have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 and a life expectancy of at least 12 weeks. Additional eligibility criteria included adequate bone marrow reserve (WBC count 3.5 x 10⁹/L, platelets 100 x 10⁹/L, hemoglobin 10 g/L, and hematocrit 30%) and liver and renal function (creatinine < 1.5 times the upper limit of normal).

Patients were excluded from the study for active infection, symptomatic CNS metastases requiring emergency radiotherapy and/or corticosteroids, serious concomitant systemic disorders, second primary malignancy (except in situ carcinoma of the cervix or nonmelanomatous skin cancers), and severe cardiovascular diseases. Patients who were pregnant or breast-feeding were not entered onto the study.

Written informed consent was obtained from each patient before entering the study. The study was conducted under the approval of the appropriate ethical review boards and the guidelines for good clinical practice. The recommendations of the Declaration of Helsinki for biomedical research involving human subjects were also followed.

Study Design and Sample Size
The study was powered at 80% to detect a difference between the comparator arms (GC and PCb) and the reference arm (VC) in response rate. The sample size needed for this study was 600 patients randomized in equal proportions to one of three treatment arms. This sample size was determined using a significance level of 5% for alpha and 20% for beta to test the hypothesis that all treatment arms were equal versus the alternative hypothesis that the comparator arms improved the response rate by 15% compared with that of the reference arm.

The randomization was centrally performed and patients were stratified by three prognostic variables: disease stage (locally advanced v metastatic disease), performance status (baseline ECOG performance status of 0 or 1 v 2), and investigational site. Patients were balanced with respect to study treatment in each stratum and for each factor using the algorithm described by Pocock and Simon.¹⁶

Treatment Schedule
On the GC arm, patients received gemcitabine 1,250 mg/m² intravenously (IV) days 1 and 8 and cisplatin 75 mg/m² (with appropriate hydration and antiemetics) day 2 of a 21-day cycle. On the PCb arm, patients received paclitaxel 225 mg/m² as a 3-hour infusion then carboplatin IV at a dose corresponding to an area under the concentration-time curve of 6 mg/mL·min, according to Calvert’s formula,¹⁷ both on day 1 every 21 days. On the VC arm, patients received vinorelbine 25 mg/m² days 1, 8, 15, and 22 as a 30-minute intravenous infusion and cisplatin 100 mg/m² IV (with appropriate hydration and antiemetics) day 1 every 28 days. After 12 weeks of treatment, vinorelbine was administered every other week.

Patients who reached stable disease received a maximum of six cycles of therapy, whereas patients demonstrating an objective response (complete or partial) continued treatment at the investigator’s discretion, for two additional courses, up to eight cycles. Patients who experienced progressive disease or unacceptable toxicity or who could not be administered drug for 6 weeks from the time of last treatment were discontinued from the study. Dose adjustments within a cycle were made on the basis of absolute neutrophil count and platelet counts measured on the day of therapy, and assessment of nonhematologic toxicities.

Baseline and Treatment Evaluations
Before entering the study, patients underwent a medical history and physical examination, tumor measurement of palpable or visual lesions, chest radiograph, full blood count, blood chemistries, urinalysis, ECG, vital signs, and calculated creatinine clearance. Additional prestudy assessments included radiologic tests (computed tomographic scan or magnetic resonance imaging) if necessary for tumor measurement or if clinical or laboratory data suggested evidence of disease in a site not assessable by other imaging modalities. The same assessment method used to determine disease status at baseline was used consistently for efficacy evaluation throughout the study.

Before each cycle, patients completed the EORTC QLQ-C30-LC13 and underwent a limited medical history, physical examination (including tumor measurements), and chest radiography. During each cycle, patients underwent blood chemistries on day 1 and a full blood count weekly. In addition, patients on the GC and VC arms had calculated creatinine clearance assessed on day 1 of each cycle. At the end of each cycle, patients were assessed for toxicity according to the National Cancer Institute common toxicity criteria version 2.0.

Before every other cycle, patients underwent radiologic imaging studies that assessed disease status. All patients who received at least two cycles of therapy were considered assessable for objective tumor response. Objective tumor response was evaluated per standard World Health Organization criteria. For unidimensionally measurable tumors, partial response was defined as a reduction from baseline of 70% of the greatest diameter of the tumor, and progressive disease was defined as an increase from baseline of more than 30%. All complete or partial responders were to be confirmed 4 weeks after the response was first documented. To validate objective responses, computed tomographic scans were subsequently submitted to an independent oncology review board.

The duration of an objective (complete or partial) response was measured from the time the response was first documented to the date of disease progression. Overall survival was measured from the date of randomization to the date of death. Time to treatment failure was defined as the period from time of randomization to disease progression or discontinuation because of death or drug-related toxicities. All randomized patients who entered the study were evaluated for safety.

Statistical Analysis
Intent-to-treat analyses were performed on data from all patients who entered the study and received treatment. Estimates of time-to-event end points were calculated using the Kaplan-Meier method¹⁸ and compared using the log-rank test. Responses were compared using Pearson’s ² test. The effects of baseline factors (performance status, brain metastases, squamous cell histology, number of metastatic sites, and disease stage) were assessed for time-to-event end points using Cox’s proportional hazards model and were assessed for response using logistic regression. Those factors that showed individual prognostic value in univariate models were assessed for joint prognostic value in a multivariate model. A final model was developed using a backward selection strategy. Treatment was added to the final model to assess its effect when adjusted for the presence of important prognostic factors.

Each scale from the EORTC QLQ-C30-LC13 instrument was analyzed using a one-way analysis of variance. Differences from baseline to the end of cycle 2 for each scale and whether this treatment difference was sustained at the end of cycle 4 were evaluated. If there was an overall treatment difference (P < .05), comparisons of each experimental arm with the control arm (VC arm) were performed.

	RESULTS

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Patient Demographics and Disease Characteristics
A total of 612 patients entered the study between August 1998 and May 2000. Of these patients, three on the PCb arm and two on the VC arm were randomized but did not receive treatment. Patient demographics and disease characteristics at baseline for the 607 patients who received treatment (205 GC, 201 PCb, and 201 VC) were well balanced across treatment groups (Table 1). Most of the patients with stage IIIB disease had N3 involvement (30 GC, 35 PCb, and 35 VC), and only a few had pleural effusion.

Efficacy outcomes for time-to-event measures are listed in Table 3. Median follow-up times for these analyses were 8.8 months (95% confidence interval [CI], 8.0 to 9.7 months) for GC, 9.3 months (95% CI, 8.2 to 10.2 months) for PCb, and 8.7 months (95% CI, 8.1 to 9.7 months) for VC. There were no differences between the experimental arms and the reference arm in overall survival, time to disease progression, and time to treatment failure. Figure 1 provides Kaplan-Meier curves by treatment arm for overall survival. Median survival times for the GC, PCb, and VC groups were 9.8, 9.9, and 9.5 months, respectively. Respective 1-year survival rates were 37%, 43%, and 37% (GC v VC, P = .484; PCb v VC, P = .105). At the time of the analysis, 450 patients (150 GC, 148 PCb, and 152 VC) had died, giving censoring rates for survival of 26.8%, 26.4%, and 24.4%, respec-tively. Kaplan-Meier curves for time to progressive disease and time to treatment failure by treatment arms are shown in Fig 2.

View larger version (16K): [in this window] [in a new window]   Fig 1. Overall survival curves for the GC, PCb, and VC arms.

View larger version (19K): [in this window] [in a new window]   Fig 2. (A) Time-to-progressive-disease curves for the GC, PCb, and VC arms. (B) Time-to-treatment-failure curves for the GC, PCb, and VC arms.

Toxicity
Grade 3/4 hematologic toxicities are listed by cycle in Table 4. For the GC and PCb arms, the percentages of cycles with grade 3/4 neutropenia (17% and 35%, respectively) and anemia (6% and 2%, respectively) were lower than the values in the VC group (43% and 7%, P < .001), whereas the incidences of grade 3/4 thrombocytopenia were higher in the experimental arms (16% and 3% v 0.1%, P < .001). No serious hemorrhagic events were noted on either arm. The number of patients with febrile neutropenia (one for GC, two for PCb, and six for VC) were low and similar across treatment groups, whereas packed RBC transfusions were significantly less on the PCb arm (P < .01). Percentages of patients who received platelet transfusions for each arm (GC 8%, PCb 2%, and VC 8%) were not consistent with the respective percentages reported for grade 3/4 thrombocytopenia.

Treatment Administration
A total of 115 patients (45 GC, 47 PCb, and 23 VC) completed study treatment. Most patients discontinued the study because of progressive disease (80 GC, 76 PCb, and 95 VC). The total number of cycles delivered for the GC, PCb, and VC arms was 825 (mean per patient, 4.0), 851 (mean per patient, 4.2), and 653 (mean per patient, 3.2), respectively. Patients on the VC arm had the highest percentages of dose reductions (17%) and omissions (19%), mainly because of hematologic toxicities. The percentages of reductions and omissions were 12% and 6% for GC and 13% and 0% for PCb, respectively. Actual dose intensities were 90.6% for gemcitabine, 100% for cisplatin (with gemcitabine), 77.4% for vinorelbine, 94.8% for cisplatin (with vinorelbine), 94.7% for paclitaxel, and 99.2% for carboplatin.

QoL
Compliance for completion of the EORTC QLQ-C30-LC13 at baseline was high, but at later cycles, the percentage of patients still receiving therapy and who completed the questionnaire decreased. On-study compliance rates are listed in Table 6.

When the same analysis was conducted after four cycles of therapy, the only scales showing treatment differences were pain, nausea/vomiting, peripheral neuropathy, and alopecia. Further analysis showed a statistical difference between the GC and VC arms in peripheral neuropathy, which favored the GC arm. This analysis also showed statistical differences between the PCb and VC arms for pain, peripheral neuropathy, and alopecia, all of which favored the VC arm. The significant parameters from cycle 2 are plotted in Fig 3. These same parameters were also plotted for cycle 4 to show whether treatment differences were sustained. Only nausea/vomiting, peripheral neuropathy, and alopecia showed sustained treatment differences.

View larger version (23K): [in this window] [in a new window]   Fig 3. Significant QoL parameters after two cycles with follow-up after four cycles. V2 and V4 for VC, G2 and G4 for GC, and P2 and P4 for PCb. #Role functioning values were inverted to reflect positive changes as worsening. *Significantly different (P < .05) from the control arm.

	DISCUSSION

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION REFERENCES

 
In advanced NSCLC, cisplatin-based chemotherapy improves survival, palliates symptoms, and is cost effective. Despite these encouraging data, most physicians are far from considering chemotherapy a standard approach for their patients.

Two other large, adequately sized, cooperative-group studies, the ECOG 1594¹⁹ and Southwest Oncology Group (SWOG) 9509²⁰ trials, have already explored the therapeutic potential of newer regimens in patients with advanced NSCLC. In the four-arm ECOG trial comparing combinations of GC, docetaxel/cisplatin, and paclitaxel (3-hour)/carboplatin to paclitaxel (24-hour)/cisplatin, survival rates on the experimental arms (7.4 to 8.2 months) were not significantly different from that of the control arm (7.8 months), except for time to progression for the GC arm, which was significantly higher than that in the control arm (4.2 v 3.4 months, respectively; P = .001). In the SWOG trial, a control regimen of VC was compared with a regimen of PCb equivalent to that of the ECOG study. Patient characteristics were essentially comparable to those of the ECOG trial. Again, no differences between arms in any efficacy end point were noted.

In this large, multicenter, randomized trial conducted by the Italian Lung Cancer Project, the comparison of two of the latest generation of doublets, GC and PCb, to the reference regimen of VC showed comparable activity in terms of overall response rate, median and 1-year survival, time to progression, and time to treatment failure. The higher response rates and improved median survival times of approximately 2 months compared with those of the ECOG and SWOG studies appear to be attributable to the lower percentage of stage IV patients included in our trial (about 80% for our study v 91% for ECOG 1594 and 89% for SWOG 9509).

Second-line therapy has been asserted as a possible explanation for the absence of any survival advantages observed between the experimental and reference arms of the ECOG 1594 and SWOG 9509 trials but, unfortunately, these data were not recorded in those trials. In our study, most of the patients who received front-line therapy on the PCb and VC arms combined received gemcitabine-based therapy at the time of relapse. Of the patients who received poststudy chemotherapy on the GC arm, half of the patients received taxanes and the other half received vinorelbine. The similarity among the three treatment arms in median time to treatment failure, time to progressive disease, and overall survival makes the possibility of any positive impact of second-line therapy questionable.

The overall toxicity profile on the VC arm was more pronounced than that of either experimental arm: a significantly higher proportion of patients were not assessable for response at cycle 2 (23% for VC v 13% for GC and 14% for PCb, P < .02) because of discontinuation attributable to adverse events or progressive disease. In addition, a lower percentage of patients on the VC arm completed four cycles or the full course of chemotherapy (40% and 25%, respectively, v 59% and 37% for GC and 62% and 46% for PCb).

Grade 3/4 neutropenia was more commonly documented with the VC regimen, and six of a total of nine episodes of febrile neutropenia were reported on this arm. Grade 3/4 thrombocytopenia was more frequent on the GC arm and was only detected at the weekly blood cell count assessment, but was not associated with any serious hemorrhagic events. Moreover, the incidence of thrombocytopenia for GC was substantially lower compared with that reported in previous trials using a 4-week schedule.^11,12,20,21 The inconsistency between the thrombocytopenia and platelet transfusion data on each arm is not clear, but may reflect variable transfusion policies or skill level in the management of hematologic toxicities.

The PCb arm was associated with the highest incidences of alopecia (grade 1/2, 52% of patients) and peripheral neuropathy (grades 1 to 3, 30% of patients), as was the VC arm for nausea/vomiting (grade 3/4, 13% of patients). The latter toxicity could be related to the higher day-1 cisplatin dose (100 mg/m²) as opposed to the 75-mg/m² dose administered on the GC arm, but these doses were chosen to ensure similar cisplatin dose intensities on both arms. On the PCb arm, peripheral neuropathy higher than grade 2 appeared cumulative, ranging from 17% at cycle 2 to 32% at cycle 6. The 7% rate of neurotoxicity (highest grade) reported on the PCb arm is similar to respective rates reported by SWOG (13%) and ECOG (10%) investigators using the same schedule.

QoL results showed little differences between the VC and GC arms. Although results after two cycles of therapy favored the PCb arm over the VC arm, results after four cycles favored the VC arm. Administration of the questionnaire at the end of the cycle may have failed to detect the effect of acute toxicities on QoL. In addition, decreased compliance may have limited the statistical power to demonstrate differences, particularly at later cycles. Other randomized studies have failed to show meaningful differences between treatment arms in QoL for similar reasons.^10-12,20

The present study failed to demonstrate a therapeutic advantage of either experimental regimen over the reference regimen in terms of survival or response. This result is entirely in keeping with the results of the ECOG and SWOG trials, providing further evidence that all of these regimens remain reasonable choices for patients with advanced NSCLC. Even though the present trial failed to show any advantage in response rate, survival, or QoL for the two experimental arms, the VC arm demonstrated greater toxicity, a significantly lower percentage of assessable patients, and a lower mean number of cycles, despite the schedule modification used to limit the toxicity reported in previous randomized studies.^9,20 These potential limitations may undermine the usefulness of VC as a reference arm for future trials. Alternative schedules of VC (ie, lower cisplatin doses or vinorelbine on days 1 and 8 every 3 weeks) require validation in the phase III setting.

It is quite likely that the efficacy of chemotherapy in NSCLC may have reached a plateau, underscoring the uncertainty of getting better results by adding a third drug or changing the sequence of the available active agents. New strategies involving combining chemotherapy with novel biologic agents appear promising. As several of these agents are currently being developed for NSCLC, the results of ongoing randomized trials are eagerly awaited.

APPENDIX
The appendix listing investigators and institutions is available online at www.jco.org.

The following investigators and institutions were actively involved in the trial: S. Novello and G. Selvaggi, Department of Clinical and Biologic Sciences, University of Torino, Turin; M. R. Migliorino, L. Poaluzzi, and R. Belli, Division of Pneumo-Oncology V, C. Forlanini Hospital, Rome; M. Lopez and P. Foggi, Division of Medical Oncology B, Regina Elena Institute, Rome; A. Maestri, F. Mazzoni, and A. Di Stefano, Division of Medical Oncology, Bellaria Hospital, Bologna; E. Barletta and M. L. Barzelloni, Division of Medical Oncology B, National Cancer Institute "G. Pascale," Naples; L. Galli and M. Antonuzzo, Division of Medical Oncology, S. Chiara Hospital, Pisa; A. R. Bianco and V. Damiano, Department of Endocrinology and Molecular and Clinical Oncology, Federico II University, Naples; L. Savoldi and V. Pajetta, Division of Medical Oncology, S. Maria Hospital, Reggio Emilia; F. Zumaglini, Division of Medical Oncology, S. Maria delle Croci Hospital, Ravenna; A. Papalardo, Division of Medical Oncology, S. Luigi and S. Curro Hospital, Catania; V. Adamo, Department of Medical Oncology, University of Messina, Messina; F. Cognetti, Division of Medical Oncology A, Regina Elena Institute, Rome; G. Belloni, Division of Medical Oncology, S. Giuseppe Hospital, Milan; S. Gasperoni, Division of Medical Oncology, S. Maria Hospital, Terni; E. Piazza and P. Candido, Division of Medical Oncology, L. Sacco Hospital, Milan; F. Gozzelino, Division of Pneumology, Infermi Hospital, Biella; O. Bertetto, Division of Medical Oncology, S. Giovanni Battista Hospital, Turin; F. Pucci and S. Salvagni, Medical Oncology Service, General Hospital, Parma; G. Cruciani and G. M. Turolla, Medical Oncology Service, Lugo; A. Santini, Division of General Medicine and Medical Oncology, St. Anna Hospital, Ferrara; E. Recaldin and V. Picece, Division of Medical Oncology, S. Cuore Hospital, Negrar (Verona); A. Favaretto, Division of Medical Oncology, Civile Hospital, Padova; G. Luporini, Division of Medical Oncology, St. Carlo Borromeo Hospital, Milan; A. Ravaioli, Division of Medical Oncology, Infermi Hospital, Rimini; S. Gardani and A. Ardizzoia, Division of Radiation Oncology, S. Gerardo Hospital, Monza; S. Cerutti, Division of Medical Oncology, University of Torino, Turin; V. Fosser, Medical Oncology Service, St. Bartolo Hospital, Vicenza; R. Felletti, Division of Pneumology, S. Martino Hospital, Genoa; A. Paccagnella, Division of Medical Oncology, Civile Hospital, Venice; E. Pasquini, Medical Oncology Service, Civile Hospital, Cattolica (Forli); L. Portalone, Division of Pneumology VI, Forlanini Hospital, Rome; G. Ferrara, Department of Pneumology I, "Vincenzo Cervello" Hospital, Palermo; R. Canaletti, Division of Medical Oncology, Civile Hospital, Piacenza; M. Aglietta, Division of Medical Oncology, Cancer Research Institute, Candiolo (Turin); P. Pronzato, Division of Medical Oncology, St. Andrea Hospital, La Spezia; and A.M. Mosconi, S. Darwish, and S. Porrozzi, Division of Medical Oncology, Policlinico Hospital, Perugia.

	ACKNOWLEDGMENTS

 
Supported by Eli Lilly and Company.

We thank Marco Pacini, Alfonso Gentile, Luca Marini, Roberta Pratolini, Mauro Caterino, Annamaria Hayden, Astra Liepa, Binh Nguyen, and Clet Niyizika for technical assistance, and Mary Alice Miller, PhD, for editorial assistance with the article.

	NOTES

 
Presented in part at the Thirty-Seventh Annual Meeting of the American Society of Clinical Oncology, San Francisco, CA, May 12-15, 2001.

	REFERENCES

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION REFERENCES

 
1. Ihde DC: Chemotherapy of lung cancer. N Engl J Med 327: 1434-1441, 1992[Medline]

2. Bunn PA Jr: The treatment of non-small cell lung cancer: Current perspectives and controversies, future directions. Semin Oncol 21: 49-59, 1994[Medline]

3. Non-Small Cell Lung Cancer Collaborative Group: Chemotherapy in non-small cell lung cancer: A meta-analysis using updated data on individual patients from 52 randomised clinical trials. BMJ 311: 899-909, 1995[Abstract/Free Full Text]

4. Lilenbaum R, Green MR: Novel chemotherapeutic agents in the treatment of non-small-cell lung cancer. J Clin Oncol 11: 1391-1402, 1993[Abstract/Free Full Text]

5. Sandler AB, Nemunaitis J, Denham C, et al: Phase III trial of gemcitabine plus cisplatin versus cisplatin alone in patients with locally advanced or metastatic non-small-cell lung cancer. J Clin Oncol 18: 122-130, 2000[Abstract/Free Full Text]

6. Wozniak AJ, Crowley JJ, Balcerzak SP, et al: Randomized trial comparing cisplatin with cisplatin plus vinorelbine in the treatment of advanced non-small-cell lung cancer: A Southwest Oncology Group study. J Clin Oncol 16: 2459-2465, 1998[Abstract]

7. von Pawel J, von Roemeling R, Gatzemeier U, et al: Tirapazamine plus cisplatin versus cisplatin in advanced non-small-cell lung cancer: A report of the international CATAPULT I study group—Cisplatin and tirapazamine in subjects with advanced previously untreated non-small-cell lung tumors. J Clin Oncol 18: 1351-1359, 2000[Abstract/Free Full Text]

8. Gatzemeier U, von Pawel J, Gottfried M, et al: Phase III comparative study of high-dose cisplatin versus a combination of paclitaxel and cisplatin in patients with advanced non-small cell lung cancer. J Clin Oncol 18: 3390-3399, 2000[Abstract/Free Full Text]

9. Le Chevalier T, Brisgand D, Douillard JY, et al: Randomized study of vinorelbine and cisplatin versus vindesine and cisplatin versus vinorelbine alone in advanced non-small-cell lung cancer: Results of a multicenter European trial including 612 patients. J Clin Oncol 12: 360-367, 1994[Abstract]

10. Crinò L, Scagliotti GV, Ricci S, et al: Gemcitabine and cisplatin versus mitomycin, ifosfamide, and cisplatin in advanced non-small-cell lung cancer: A randomized phase III study of the Italian Lung Cancer Project. J Clin Oncol 17: 3522-3530, 1999[Abstract/Free Full Text]

11. Cardenal F, Lopez-Cabrerizo MP, Anton A, et al: Randomized phase III study of gemcitabine-cisplatin versus etoposide-cisplatin in the treatment of locally advanced or metastatic non–small-cell lung cancer. J Clin Oncol 17: 12-18, 1999[Abstract/Free Full Text]

12. Bonomi P, Kim K, Fairclough D, et al: 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. J Clin Oncol 18: 623-631, 2000[Abstract/Free Full Text]

13. Giaccone G, Splinter TA, Debruyne C, et al: Randomized study of paclitaxel-cisplatin versus cisplatin-teniposide in patients with advanced non-small-cell lung cancer: The European Organization for Research and Treatment of Cancer Lung Cancer Cooperative Group. J Clin Oncol 16: 2133-2141, 1998[Abstract]

14. Belani CP, Natale RB, Lee JS, et al: Randomized phase III trial comparing cisplatin/etoposide versus carboplatin/paclitaxel in advanced and metastatic non-small cell lung cancer (NSCLC). Proc Am Soc Clin Oncol 17: 455a, 1998 (abstr 1751)

15. Bergman B, Aaronson NK, Ahmedzai S, et al: The EORTC QLQ-LC13: A modular supplement to the EORTC Core Quality of Life Questionnaire (QLQ-C30) for use in lung cancer clinical trials. Eur J Cancer 30A: 635-642, 1994[CrossRef][Medline]

16. Pocock S, Simon R: Sequential treatment assignment with balancing of prognostic factors in the controlled clinical trial. Biometrics 31: 103-115, 1975[CrossRef][Medline]

17. Calvert AH, Newell DR, Gumbrell LA, et al: Carboplatin dosage: Prospective evaluation of a simple formula based on renal function. J Clin Oncol 7: 1748-1756, 1989[Abstract]

18. Kaplan EL, Meier P: Nonparametric estimation from incomplete observations. J Am Stat Assoc 53: 457-481, 1959[CrossRef]

19. Schiller JH, Harrington D, Belani C, et al: Comparison of four chemotherapy regimens for advanced non-small cell lung cancer. N Engl J Med 346: 92-98, 2002[Abstract/Free Full Text]

20. Kelly K, Crowley J, Bunn PA Jr, et al: 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. J Clin Oncol 19: 3210-3218, 2001[Abstract/Free Full Text]

21. Rinaldi M, Crinò L, Scagliotti GV, et al: A three-week schedule of gemcitabine-cisplatin in advanced non-small-cell lung cancer with two different cisplatin dose levels: A phase II randomized trial. Ann Oncol 11: 1295-1300, 2000[Abstract/Free Full Text]

Submitted February 13, 2002; accepted July 17, 2002.

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				G. M. Strauss, J. E. Herndon II, M. A. Maddaus, D. W. Johnstone, E. A. Johnson, D. H. Harpole, H. H. Gillenwater, D. M. Watson, D. J. Sugarbaker, R. L. Schilsky, et al. Adjuvant Paclitaxel Plus Carboplatin Compared With Observation in Stage IB Non-Small-Cell Lung Cancer: CALGB 9633 With the Cancer and Leukemia Group B, Radiation Therapy Oncology Group, and North Central Cancer Treatment Group Study Groups J. Clin. Oncol., November 1, 2008; 26(31): 5043 - 5051. [Abstract] [Full Text] [PDF]

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				L. H. Einhorn First-Line Chemotherapy for Non-Small-Cell Lung Cancer: Is There a Superior Regimen Based on Histology? J. Clin. Oncol., July 20, 2008; 26(21): 3485 - 3486. [Full Text] [PDF]

				R. Ramlau, P. Zatloukal, J. Jassem, P. Schwarzenberger, S. V. Orlov, M. Gottfried, J. R. Pereira, G. Temperley, R. Negro-Vilar, S. Rahal, et al. Randomized Phase III Trial Comparing Bexarotene (L1069-49)/Cisplatin/Vinorelbine With Cisplatin/Vinorelbine in Chemotherapy-Naive Patients With Advanced or Metastatic Non-Small-Cell Lung Cancer: SPIRIT I J. Clin. Oncol., April 10, 2008; 26(11): 1886 - 1892. [Abstract] [Full Text] [PDF]

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				A. Ardizzoni, L. Boni, M. Tiseo, F. V. Fossella, J. H. Schiller, M. Paesmans, D. Radosavljevic, A. Paccagnella, P. Zatloukal, P. Mazzanti, et al. Cisplatin- Versus Carboplatin-Based Chemotherapy in First-Line Treatment of Advanced Non-Small-Cell Lung Cancer: An Individual Patient Data Meta-analysis J Natl Cancer Inst, June 6, 2007; 99(11): 847 - 857. [Abstract] [Full Text] [PDF]

				S Novello, P Bruzzi, C Barone, R Buosi, A Masotti, G Michetti, M Fioretti, S Barbera, M Spatafora, L Garetto, et al. Phase III study in stage IV non-small-cell lung cancer patients treated with two courses of cisplatin/gemcitabine followed by a randomization to three additional courses of the same combination or gemcitabine alone Ann. Onc., May 1, 2007; 18(5): 903 - 908. [Abstract] [Full Text] [PDF]

				U. Gatzemeier, A. Pluzanska, A. Szczesna, E. Kaukel, J. Roubec, F. De Rosa, J. Milanowski, H. Karnicka-Mlodkowski, M. Pesek, P. Serwatowski, et al. Phase III Study of Erlotinib in Combination With Cisplatin and Gemcitabine in Advanced Non-Small-Cell Lung Cancer: The Tarceva Lung Cancer Investigation Trial J. Clin. Oncol., April 20, 2007; 25(12): 1545 - 1552. [Abstract] [Full Text] [PDF]

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				C. J. Langer Mind Your Elders: Therapeutic Implications of Epidermal Growth Factor Receptor Inhibition in Older Patients With Advanced Non-Small-Cell Lung Cancer J. Clin. Oncol., March 1, 2007; 25(7): 751 - 753. [Full Text] [PDF]

				P Bidoli, N Zilembo, D Cortinovis, L Mariani, L Isa, E Aitini, D Cullura, F Pari, P Nova, M Mancin, et al. Randomized phase II three-arm trial with three platinum-based doublets in metastatic non-small-cell lung cancer. An Italian Trials in Medical Oncology study Ann. Onc., March 1, 2007; 18(3): 461 - 467. [Abstract] [Full Text] [PDF]

				P Comella, G Filippelli, G De Cataldis, B Massidda, G Frasci, L Maiorino, C Putzu, S Mancarella, S Palmeri, R Cioffi, et al. Efficacy of the combination of cisplatin with either gemcitabine and vinorelbine or gemcitabine and paclitaxel in the treatment of locally advanced or metastatic non-small-cell lung cancer: a phase III randomised trial of the Southern Italy Cooperative Oncology Group (SICOG 0101) Ann. Onc., February 1, 2007; 18(2): 324 - 330. [Abstract] [Full Text] [PDF]

				Y Ohe, Y Ohashi, K Kubota, T Tamura, K Nakagawa, S Negoro, Y Nishiwaki, N Saijo, Y Ariyoshi, M Fukuoka, et al. Randomized phase III study of cisplatin plus irinotecan versus carboplatin plus paclitaxel, cisplatin plus gemcitabine, and cisplatin plus vinorelbine for advanced non-small-cell lung cancer: Four-Arm Cooperative Study in Japan Ann. Onc., February 1, 2007; 18(2): 317 - 323. [Abstract] [Full Text] [PDF]

				C. Belani, S Dakhil, D. Waterhouse, C. Desch, D. Rooney, R. Clark, M. Monberg, Z Ye, and C. Obasaju Randomized phase II trial of gemcitabine plus weekly versus three-weekly paclitaxel in previously untreated advanced non-small-cell lung cancer Ann. Onc., January 1, 2007; 18(1): 110 - 115. [Abstract] [Full Text] [PDF]

				P Ceppi, M Volante, S Novello, I Rapa, K. Danenberg, P. Danenberg, A Cambieri, G Selvaggi, S Saviozzi, R Calogero, et al. ERCC1 and RRM1 gene expressions but not EGFR are predictive of shorter survival in advanced non-small-cell lung cancer treated with cisplatin and gemcitabine Ann. Onc., December 1, 2006; 17(12): 1818 - 1825. [Abstract] [Full Text] [PDF]

				J Cadranel, D Garfield, A Lavole, M Wislez, B Milleron, and C Mayaud Lung cancer in HIV infected patients: facts, questions and challenges. Thorax, November 1, 2006; 61(11): 1000 - 1008. [Abstract] [Full Text] [PDF]

				R. Govindan, J. Crowley, L. Schwartzberg, P. Kennedy, C. Williams, B. Ekstrand, A. Sandler, D. Jaunakais, V. Bolejack, and R. Ghalie Phase II Trial of Bexarotene Capsules in Patients With Advanced Non-Small-Cell Lung Cancer After Failure of Two or More Previous Therapies J. Clin. Oncol., October 20, 2006; 24(30): 4848 - 4854. [Abstract] [Full Text] [PDF]

				J. R. Molina, A. A. Adjei, and J. R. Jett Advances in Chemotherapy of Non-small Cell Lung Cancer. Chest, October 1, 2006; 130(4): 1211 - 1219. [Abstract] [Full Text] [PDF]

				A. Inoue, T. Suzuki, T. Fukuhara, M. Maemondo, Y. Kimura, N. Morikawa, H. Watanabe, Y. Saijo, and T. Nukiwa Prospective Phase II Study of Gefitinib for Chemotherapy-Naive Patients With Advanced Non-Small-Cell Lung Cancer With Epidermal Growth Factor Receptor Gene Mutations J. Clin. Oncol., July 20, 2006; 24(21): 3340 - 3346. [Abstract] [Full Text] [PDF]

				R. Booton, P. Lorigan, H. Anderson, S. Baka, L. Ashcroft, M. Nicolson, M. O'Brien, D. Dunlop, K. O'Byrne, V. Laurence, et al. A phase III trial of docetaxel/carboplatin versus mitomycin C/ifosfamide/cisplatin (MIC) or mitomycin C/vinblastine/cisplatin (MVP) in patients with advanced non-small-cell lung cancer: a randomised multicentre trial of the British Thoracic Oncology Group (BTOG1) Ann. Onc., July 1, 2006; 17(7): 1111 - 1119. [Abstract] [Full Text] [PDF]

				M. A. Socinski, A. Ivanova, K. Bakri, J. Wall, M. Q. Baggstrom, T. A. Hensing, A. Mears, M. Tynan, J. Beaumont, A. H. Peterman, et al. A randomized phase II trial comparing every 3-weeks carboplatin/paclitaxel with every 3-weeks carboplatin and weekly paclitaxel in advanced non-small cell lung cancer Ann. Onc., January 1, 2006; 17(1): 104 - 109. [Abstract] [Full Text] [PDF]

				F. Robert, G. Blumenschein, R. S. Herbst, F. V. Fossella, J. Tseng, M. N. Saleh, and M. Needle Phase I/IIa Study of Cetuximab With Gemcitabine Plus Carboplatin in Patients With Chemotherapy-Naive Advanced Non-Small-Cell Lung Cancer J. Clin. Oncol., December 20, 2005; 23(36): 9089 - 9096. [Abstract] [Full Text] [PDF]

				H. Wakelee and C. P. Belani Optimizing First-Line Treatment Options for Patients with Advanced NSCLC Oncologist, October 1, 2005; 10(suppl_3): 1 - 10. [Abstract] [Full Text] [PDF]

				J. J. Lee and L. Feng Randomized Phase II Designs in Cancer Clinical Trials: Current Status and Future Directions J. Clin. Oncol., July 1, 2005; 23(19): 4450 - 4457. [Abstract] [Full Text] [PDF]

				M. L de Lemos Vinorelbine and venous irritation: optimal parenteral administration Journal of Oncology Pharmacy Practice, June 1, 2005; 11(2): 79 - 81. [Abstract] [PDF]

				V. Georgoulias, A. Ardavanis, X. Tsiafaki, A. Agelidou, P. Mixalopoulou, O. Anagnostopoulou, P. Ziotopoulos, M. Toubis, K. Syrigos, N. Samaras, et al. Vinorelbine Plus Cisplatin Versus Docetaxel Plus Gemcitabine in Advanced Non-Small-Cell Lung Cancer: A Phase III Randomized Trial J. Clin. Oncol., May 1, 2005; 23(13): 2937 - 2945. [Abstract] [Full Text] [PDF]

				J. R. Goffin, I. C. Anderson, J. G. Supko, J. P. Eder Jr., G. I. Shapiro, T. J. Lynch, M. Shipp, B. E. Johnson, and A. T. Skarin Phase I Trial of the Matrix Metalloproteinase Inhibitor Marimastat Combined with Carboplatin and Paclitaxel in Patients with Advanced Non-Small Cell Lung Cancer Clin. Cancer Res., May 1, 2005; 11(9): 3417 - 3424. [Abstract] [Full Text] [PDF]

				S. Baka, L. Ashcroft, H. Anderson, M. Lind, P. Burt, R. Stout, I. Dowd, D. Smith, P. Lorigan, and N. Thatcher Randomized Phase II Study of Two Gemcitabine Schedules for Patients With Impaired Performance Status (Karnofsky performance status <= 70) and Advanced Non-Small-Cell Lung Cancer J. Clin. Oncol., April 1, 2005; 23(10): 2136 - 2144. [Abstract] [Full Text] [PDF]

				J.-L. Pujol, J.-L. Breton, R. Gervais, P. Rebattu, A. Depierre, J.-F. Morere, B. Milleron, D. Debieuvre, D. Castera, P.-J. Souquet, et al. Gemcitabine-docetaxel versus cisplatin-vinorelbine in advanced or metastatic non-small-cell lung cancer: a phase III study addressing the case for cisplatin Ann. Onc., April 1, 2005; 16(4): 602 - 610. [Abstract] [Full Text] [PDF]

				S. Kobayashi, T. J. Boggon, T. Dayaram, P. A. Janne, O. Kocher, M. Meyerson, B. E. Johnson, M. J. Eck, D. G. Tenen, and B. Halmos EGFR Mutation and Resistance of Non-Small-Cell Lung Cancer to Gefitinib N. Engl. J. Med., February 24, 2005; 352(8): 786 - 792. [Abstract] [Full Text] [PDF]

				G. V. Scagliotti, C. Kortsik, G. G. Dark, A. Price, C. Manegold, R. Rosell, M. O'Brien, P. M. Peterson, D. Castellano, G. Selvaggi, et al. Pemetrexed Combined with Oxaliplatin or Carboplatin as First-Line Treatment in Advanced Non-Small Cell Lung Cancer: A Multicenter, Randomized, Phase II Trial Clin. Cancer Res., January 15, 2005; 11(2): 690 - 696. [Abstract] [Full Text] [PDF]

				J.-Y. Douillard, R. Gervais, G. Dabouis, A. Le Groumellec, M. D'Arlhac, D. Spaeth, B. Coudert, D. Caillaud, A. Monnier, C. Clary, et al. Sequential two-line strategy for stage IV non-small-cell lung cancer: docetaxel-cisplatin versus vinorelbine-cisplatin followed by cross-over to single-agent docetaxel or vinorelbine at progression: final results of a randomised phase II study Ann. Onc., January 1, 2005; 16(1): 81 - 89. [Abstract] [Full Text] [PDF]

				Y. Hu, G. Bebb, S. Tan, R. Ng, H. Yan, J. R. Sartor, L. D. Mayer, and M. B. Bally Antitumor Efficacy of Oblimersen Bcl-2 Antisense Oligonucleotide Alone and in Combination with Vinorelbine in Xenograft Models of Human Non-Small Cell Lung Cancer Clin. Cancer Res., November 15, 2004; 10(22): 7662 - 7670. [Abstract] [Full Text] [PDF]

				C. Monnerat, T. Le Chevalier, K. Kelly, C. K. Obasaju, J. Brahmer, S. Novello, T. Nakamura, A. M. Liepa, L. Bozec, P. A. Bunn Jr, et al. Phase II Study of Pemetrexed-Gemcitabine Combination in Patients with Advanced-Stage Non-Small Cell Lung Cancer Clin. Cancer Res., August 15, 2004; 10(16): 5439 - 5446. [Abstract] [Full Text] [PDF]

				G. P. Stathopoulos, M. Veslemes, N. Georgatou, D. Antoniou, P. Giamboudakis, K. Katis, D. Tsavdaridis, S. K. Rigatos, I. Dimitroulis, S. Bastani, et al. Front-line paclitaxel-vinorelbine versus paclitaxel-carboplatin in patients with advanced non-small-cell lung cancer: a randomized phase III trial Ann. Onc., July 1, 2004; 15(7): 1048 - 1055. [Abstract] [Full Text] [PDF]

				J. R. Rigas Taxane-Platinum Combinations in Advanced Non-Small Cell Lung Cancer: A Review Oncologist, June 2, 2004; 9(suppl_2): 16 - 23. [Abstract] [Full Text] [PDF]

				J. D. Winegarden, A. M. Mauer, G. A. Otterson, C. M. Rudin, M. A. Villalona-Calero, V. J. Lanzotti, L. Szeto, K. Kasza, P. C. Hoffman, and E. E. Vokes A phase II study of oxaliplatin and paclitaxel in patients with advanced non-small-cell lung cancer Ann. Onc., June 1, 2004; 15(6): 915 - 920. [Abstract] [Full Text] [PDF]

				L. C. Pulling, B. R. Vuillemenot, J. A. Hutt, T. R. Devereux, and S. A. Belinsky Aberrant Promoter Hypermethylation of the Death-Associated Protein Kinase Gene Is Early and Frequent in Murine Lung Tumors Induced by Cigarette Smoke and Tobacco Carcinogens Cancer Res., June 1, 2004; 64(11): 3844 - 3848. [Abstract] [Full Text] [PDF]

				M. Dediu Should We Discard Vinorelbine Plus Cisplatin From the First-Line Therapy of Advanced Non-Small-Cell Lung Cancer? J. Clin. Oncol., April 1, 2004; 22(7): 1345 - 1347. [Full Text] [PDF]

				C. Gridelli, A. Ardizzoni, T. Le Chevalier, C. Manegold, F. Perrone, N. Thatcher, N. van Zandwijk, M. Di Maio, O. Martelli, and F. De Marinis Treatment of advanced non-small-cell lung cancer patients with ECOG performance status 2: results of an European Experts Panel Ann. Onc., March 1, 2004; 15(3): 419 - 426. [Abstract] [Full Text] [PDF]

				R. Rosell, K. D. Danenberg, V. Alberola, G. Bepler, J. J. Sanchez, C. Camps, M. Provencio, D. Isla, M. Taron, P. Diz, et al. Ribonucleotide Reductase Messenger RNA Expression and Survival in Gemcitabine/Cisplatin-Treated Advanced Non-Small Cell Lung Cancer Patients Clin. Cancer Res., February 15, 2004; 10(4): 1318 - 1325. [Abstract] [Full Text] [PDF]

				T. Baetz, A. Belch, S. Couban, K. Imrie, J. Yau, R. Myers, K. Ding, N. Paul, L. Shepherd, J. Iglesias, et al. Gemcitabine, dexamethasone and cisplatin is an active and non-toxic chemotherapy regimen in relapsed or refractory Hodgkin's disease: a phase II study by the National Cancer Institute of Canada Clinical Trials Group Ann. Onc., December 1, 2003; 14(12): 1762 - 1767. [Abstract] [Full Text] [PDF]

				S. A. Belinsky, D. M. Klinge, C. A. Stidley, J.-P. Issa, J. G. Herman, T. H. March, and S. B. Baylin Inhibition of DNA Methylation and Histone Deacetylation Prevents Murine Lung Cancer Cancer Res., November 1, 2003; 63(21): 7089 - 7093. [Abstract] [Full Text] [PDF]

				B. E. Johnson Adjuvant Chemotherapy for Non-Small-Cell Lung Cancer: The End of the Beginning J Natl Cancer Inst, October 1, 2003; 95(19): 1422 - 1424. [Full Text] [PDF]

				V. Alberola, C. Camps, M. Provencio, D. Isla, R. Rosell, C. Vadell, I. Bover, A. Ruiz-Casado, P. Azagra, U. Jimenez, et al. Cisplatin Plus Gemcitabine Versus a Cisplatin-Based Triplet Versus Nonplatinum Sequential Doublets in Advanced Non-Small-Cell Lung Cancer: A Spanish Lung Cancer Group Phase III Randomized Trial J. Clin. Oncol., September 1, 2003; 21(17): 3207 - 3213. [Abstract] [Full Text] [PDF]

				P. Harper, T. Plunkett, and D. Khayat Quality Trials and Quality of Life in Non-Small-Cell Lung Cancer J. Clin. Oncol., August 15, 2003; 21(16): 3007 - 3008. [Full Text] [PDF]

				F. Fossella, J. R. Pereira, J. von Pawel, A. Pluzanska, V. Gorbounova, E. Kaukel, K. V. Mattson, R. Ramlau, A. Szczesna, P. Fidias, et al. 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 J. Clin. Oncol., August 15, 2003; 21(16): 3016 - 3024. [Abstract] [Full Text] [PDF]

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