|
Advertisement |
|
|
||
 |
|
|||||
|
|||||
|
 |
||||||
|
||||||
|
||||||
|
Journal of Clinical Oncology, Vol 25, No 29 (October 10), 2007: pp. 4663-4669 © 2007 American Society of Clinical Oncology. DOI: 10.1200/JCO.2007.12.5708 Cisplatin Plus Gemcitabine or Vinorelbine for Elderly Patients With Advanced Non–Small-Cell Lung Cancer: The MILES-2P Studies
From the Division of Medical Oncology, S. Giuseppe Moscati Hospital, Avellino; the Chemotherapy Unit and the Department of Pneumooncology, Monaldi Hospital, the Division of Medical Oncology B and the Clinical Trials Unit, National Cancer Institute, and the Department of Medicine and Public Health, Second University, Naples; the Division of Medical Oncology II, Istituto Oncologico Veneto, Padua; the Division of Medical Oncology A, CRO, Aviano; the Division of Medical Oncology, S. Maria del Carmine Hospital, Rovereto; the Division of Medical Oncology, L. Sacco Hospital, Milan; the Division of Medical Oncology, Oncologic Hospital, Bari; Medical Oncology, S. Carlo Hospital, Potenza; and the Division of Medical Oncology, A.Cardarelli Hospital, Campobasso, Italy Address reprint requests to Cesare Gridelli, MD, Division of Medical Oncology, S.G. Moscati Hospital, Via Circumvallazione, 68, Contrada Amoretta, 83100 Avellino, Italy; e-mail: cgridelli{at}libero.it
Purpose Two phase I/II trials were done to evaluate the feasibility of cisplatin combined with gemcitabine or vinorelbine in elderly patients with advanced non–small-cell lung cancer (NSCLC). Patients and Methods Patients with advanced NSCLC who were older than 70 years of age and who had a performance status of 0 to 1 were eligible. Cisplatin was given on day 1 (a starting dose of 50 mg/m2 with increasing increments of 10 mg/m2 at each level) and gemcitabine (1,000 mg/m2) or vinorelbine (25 mg/m2) on days 1 and 8. Cycles were repeated every 21 days. A two-stage flexible optimal design was applied in the phase II study, and unacceptable toxicity was the primary end point. Results Overall, 159 patients were enrolled: 38 in phase I and 121 in phase II studies. Cisplatin was feasible at 60 mg/m2 with gemcitabine and at 40 mg/m2 with vinorelbine. With the former combination, 50 of 60 (83.3%) patients were treated without unacceptable toxicity; objective responses were reported in 26 of 60 patients (43.5%; 95% CI, 30.6 to 56.8); median progression-free and overall survivals were 25.3 and 43.6 weeks, respectively. With the latter combination, 50 (82.0%) of 61 patients were treated without unacceptable toxicity; objective responses were reported in 22 of 61 patients (36.1%; 95% CI, 24.2 to 49.4); median progression-free and overall survivals were 21.1 and 33.1 weeks, respectively. Conclusion Both cisplatin (60 mg/m2) plus gemcitabine and cisplatin (40 mg/m2) plus vinorelbine are feasible and active in the treatment of elderly patients with advanced NSCLC. The former combination, which provides a higher dose of cisplatin, deserves comparison versus single-agent chemotherapy in this setting of patients.
Non–small-cell lung cancer (NSCLC) is the most common cancer in the world and is the leading cause of cancer-related deaths in Western countries.1 According to US statistics for years 2000 to 2004, two thirds of lung cancer cases were diagnosed in patients older than 65 years, and one third were diagnosed among those older than 75 years.2 Thus, NSCLC in elderly patients is an increasingly common problem faced by oncologists. Moreover, at the time of diagnosis, the majority of patients already have metastatic disease, and systemic, palliative treatment is the only therapeutic option. In the Elderly Lung Cancer Vinorelbine Italian Study (ELVIS), the first randomized trial dedicated to elderly patients with NSCLC, single-agent vinorelbine showed superiority over supportive care alone, in terms of both survival and quality of life.3 However, in the subsequent Multicenter Italian Lung Cancer in the Elderly Study (MILES), the combination of gemcitabine and vinorelbine failed to show any advantage over either agent alone.4 Therefore, with the evidence currently available, single-agent chemotherapy with vinorelbine or gemcitabine can be considered a recommended option for elderly patients with advanced NSCLC.5,6 Cisplatin is the standard treatment for advanced NSCLC,6 but concern exists about its tolerability and feasibility in the elderly. Although recent evidence indicates that the pharmacokinetics of cisplatin are not different between elderly and nonelderly patients,7 retrospective analyses of studies in advanced NSCLC have suggested that elderly patients might have more profound myelotoxicity and a greater risk of chemotherapy-related death from cisplatin administration compared with younger patients.8,9 Hence, prospective clinical trials dedicated to platinum-based chemotherapy for elderly patients are warranted. However, before planning a phase III trial comparing cisplatin-based chemotherapy with single-agent treatment (vinorelbine or gemcitabine), the feasibility of a cisplatin-containing regimen needs to be demonstrated prospectively in trials dedicated to elderly patients with advanced NSCLC; this will reduce problems arising from selection biases. Thus, the aims of the present project that includes two parallel phase I/II trials were to determine the recommended dose of cisplatin in combination with gemcitabine or vinorelbine and to evaluate the feasibility of such combinations in the treatment of elderly patients with advanced NSCLC.
Study Design We conducted two phase I/II studies of cisplatin plus gemcitabine and cisplatin plus vinorelbine in elderly patients with advanced NSCLC. In the phase I portion of the two studies, cisplatin was given at a starting dose of 50 mg/m2 (level 0) in combination with gemcitabine or vinorelbine, both given at a fixed dose. Planned dose-levels of cisplatin were as follows: 50 mg/m2 (level 0), 60 mg/m2 (level +1), 70 mg/m2 (level +2) and 40 mg/m2 (level –1, used if level 0 was unfeasible). Less than two unacceptable toxicities per six patients in the first three cycles of therapy at each dose-level were required to escalate the dose-level. In the phase II part of the two studies, a two-stage, flexible design10 was applied at the feasible doses of cisplatin in combination with gemcitabine or vinorelbine. The primary outcome of the phase II studies was the feasibility of the combination, defined as the lack of unacceptable toxicity in the first three cycles of treatment. The minimum acceptable rate (P0) and the hoped-for rate (P1) of patients able to receive the first three cycles of treatment without unacceptable toxicity were set equal to 70% and 85%, respectively; type I and type II errors were both set equal to 0.10. For each study, 19 to 26 patients had to be enrolled at the first stage, and at least 14 to 19 of them had to be treated without unacceptable toxicity during cycles 1 to 3, in order to proceed to the second stage. At the end of the second stage, 53 to 60 patients were planned, and at least 41 to 47 patients without unacceptable toxicity were required to conclude with a positive result. Secondary end points were tumor response, overall survival (OS), and progression-free survival (PFS). Tumor response was assessed at the end of the third and sixth cycle of chemotherapy by using Response Evaluation Criteria in Solid Tumors (RECIST) Group criteria. OS was calculated from the date of randomization to the date of death, or to the date of last follow-up for living patients. PFS was defined as the time from the date of randomization to the date of progression of disease, or to the date of death for patients dying without progression, or to the date of last follow-up for patients alive and without progression at the end of the study. Patients were allocated to the studies according to the availability of the treatment cohorts for phase I. Because of prolonged duration of the phase I trial with the vinorelbine combination, the second phases of the two studies were never overlapping. Patient assignment was performed centrally by a phone call to the coordinating center. In the dose-finding trial, patients who refused treatment or progressed during the first three cycles could be replaced.
Eligibility Criteria
Treatment
All treatments were repeated every 3 weeks, for a maximum of six cycles, unless disease progression or unacceptable toxicity occurred. On days 1 and 8 of each cycle, the minimum requirements to receive chemotherapy were as follows: absolute neutrophil count
Evaluation of Patients
From June 2002 to November 2004, 159 patients were enrolled. Baseline characteristics of patients are summarized in Table 1.
Study 1: Cisplatin Plus Gemcitabine From June 2002 to June 2003, 19 patients were enrolled onto the dose-finding trial; three subsequent cohorts of patients were treated with cisplatin at 50, 60, and 70 mg/m2 (Table 2). At the dose of 60 mg/m2, one patient was not assessed for toxicity across cycles 1 to 3 because of death, resulting from progressive disease, after cycle 1; in the six assessable patients, one unacceptable toxicity was observed (grade 3 fever after cycle 1 completion). At the dose of 70 mg/m2, two of six patients developed an unacceptable toxicity: a grade 2 hypersensitivity reaction and a grade 3 infection after cycle 2. Therefore, according to the design, cisplatin on day 1 was considered feasible at 60 mg/m2 when administered in combination with gemcitabine at the dose of 1,000 mg/m2 on days 1 and 8.
From July 2003 to February 2004, 60 patients entered the phase II trial of cisplatin plus gemcitabine. After enrollment, one patient was found ineligible because of age (67 years old) but was included in the analyses. Fifty patients (83.3%; 95% CI, 71.5 to 91.7) were treated without evidence of unacceptable toxicity during cycles 1 to 3. Main hematologic and nonhematologic toxicities were as follows: grade 3 to 4 neutropenia (20.0%), grade 3 anemia (5.0%), RBCs transfusion (8.3%), grade 3 to 4 thrombocytopenia (10.0%), febrile neutropenia (3.4%), grade 2 to 3 heart-rhythm toxicity (5.0%), grade 2 to 3 general cardiac toxicity (6.6%), and grade 2 renal toxicity (6.7%; Table 3). Twenty-six partial responses were recorded, which corresponded to a response rate of 43.3% (95% CI, 30.6 to 56.8). Median PFS and OS rates were 25.3 (95% CI, 22.6 to 32) and 43.6 weeks (95% CI, 35 to 56.3), respectively (Table 4). The rates of surviving patients at 6 and 12 months were 82.7% and 41.3%, respectively. Kaplan-Meier estimated curves of PFS and OS rates are reported in Figure 1.
Study 2: Cisplatin Plus Vinorelbine From October 2002 to January 2004, 19 patients were enrolled onto the dose-finding trial (Table 2) in two subsequent cohorts. Nine patients were enrolled onto the first cohort of cisplatin administration at 50 mg/m2; four of them could not be assessed for toxicity. One patient was found ineligible after enrollment because of baseline anemia. Three patients did not complete three cycles of treatment, one because of spontaneous pneumothorax (unrelated to treatment) after cycle 1, one because of refusal after cycle 1, and one because of disease progression after cycle 2. Two unacceptable toxicities were observed in the first cohort: grade 3 anorexia after cycle 1 and a death from a suspected myocardial infarction after cycle 3. Therefore, this dose-level was considered unfeasible, and the dose of cisplatin was reduced to 40 mg/m2 (level –1). Ten patients were enrolled in the second cohort; four patients could not be assessed for toxicity, two cases because of refusal after cycle 1 and two cases because of progressive disease after cycle 1. Among the six assessable patients, one unacceptable toxicity, which consisted of grade 2 pulmonary toxicity combined with grade 2 fatigue, was observed after cycle 1. Therefore, according to the design, cisplatin at day 1 was considered feasible at 40 mg/m2 in combination with vinorelbine administered at the dose of 25 mg/m2 on days 1 and 8. From April 2004 to November 2004, 61 patients entered the phase II trial of cisplatin at 40 mg/m2 plus vinorelbine. Fifty patients (82.0%; 95% CI, 70.0 to 90.6) experienced no unacceptable toxicity. One toxic death occurred and was attributed to febrile neutropenia. The main hematologic and nonhematologic toxicities were as follows: grade 3 to 4 neutropenia (22.9%), febrile neutropenia (4.8%), grade 3 anemia (4.9%), grade 2 heart-rhythm toxicity (1.6%), grade 3 general cardiac toxicity (1.6%), grade 2 to 3 neurologic toxicity (4.9%), and grade 2 renal toxicity (3.3%; Table 3). Six patients (9.8%) required transfusions of red blood cells. Twenty-two partial responses were recorded, which corresponded to a response rate of 36.1% (95% CI, 24.2 to 49.4). Median PFS and OS rates were 21.1 (95% CI, 15.9 to 28.4) and 33.1 weeks (95% CI, 23.1 to 57.7), respectively (Table 4). The rates of surviving patients at 6 and 12 months were 56.6% and 37.1%, respectively. Kaplan-Meier curves of PFS and OS rates are reported in Figure 2.
To plan a phase III trial to assess the efficacy of cisplatin-based chemotherapy in elderly patients with NSCLC, the feasibility of a cisplatin-containing regimen needed to be demonstrated prospectively. The present study is, to our best knowledge, the first in the literature that performed a prospective dose-finding evaluation of cisplatin in combination with gemcitabine or vinorelbine and that tested the feasibility of two such combinations, at the recommended dose of cisplatin, in the treatment of elderly patients with advanced NSCLC. In study 1, cisplatin was feasible at 60 mg/m2 in combination with gemcitabine; at this dose, the combination yielded an acceptable level of toxicity and was active in the second phase of the trial. In study 2, cisplatin was feasible at a lower dose of 40 mg/m2 in combination with vinorelbine; at this dose, the combination was still feasible and quite active, but one toxic death occurred. We acknowledge that the higher rate of patients with performance status 1 in the cisplatin plus vinorelbine arm in phase I could have affected tolerability. We also acknowledge that some of the unacceptable toxic events (pulmonary and suspected myocardial infarction) in the same arm might be confounded by typical concomitant diseases of patients with NSCLC; however, this was not the case based on the comorbidity data collected at baseline. Taking into account these results, we believe the combination of cisplatin plus gemcitabine deserves a phase III comparison versus single-agent chemotherapy in elderly patients with advanced NSCLC.
To date, evidence to support the use of platinum agents in elderly patients with advanced NSCLC comes only from retrospective analyses of subgroups of elderly patients who were enrolled into randomized trials that did not require an upper age limit in the inclusion criteria. These analyses show a similar outcome of platinum-based therapy for elderly patients compared with their younger counterparts in terms of response rate, OS, and quality of life.8,11-16 However, these data should be interpreted cautiously, because retrospective subgroup analyses are encumbered by selection bias.17 Recently, the North Central Cancer Treatment Group performed a pooled analysis of elderly patients who participated in elderly-specific trials (inclusion age Interest in reproducing the efficacy of a platinum-based chemotherapy in elderly patients resulted in the testing of combinations of third-generation cytotoxic agents with cisplatin or carboplatin in modified schedules, such as at low doses or as a weekly administration, in the search for active and well-tolerated treatment.19-26 The combination of cisplatin and gemcitabine has already been tested prospectively in the elderly population as well. Feliu et al27 have evaluated the feasibility, toxicity, and activity of the combination of low-dose cisplatin (50 mg/m2) and gemcitabine in a phase II study involving elderly patients with advanced NSCLC. This patient population was older than 70 years of age, as was the case in our trial. The chemotherapy regimen was well tolerated. No patient developed grade 4 toxicity. Grade 3 hematologic toxicities were neutropenia (13%), anemia (2%), and thrombocytopenia (2%). A response rate of 35% (95% CI, 28% to 52%) and a median OS rate of 44 weeks were recorded. The authors concluded that the combination of low-dose cisplatin and gemcitabine for elderly patients with advanced NSCLC is an active and well-tolerated chemotherapeutic approach. These results are similar to those of our trial, but we had the possibility to administer cisplatin at a higher dose (60 v 50 mg/m2) because of the preliminary dose-finding study. Also, Berardi et al28 evaluated a specifically designed combination of cisplatin and gemcitabine administered to ederly patients in a prospective phase II study.28 They found that this regimen is active and well-tolerated, but they used a weekly schedule of cisplatin (35 mg/m2 on days 1, 8, and 15 every 28 days) that is not considered a standard approach in the treatment of NSCLC, because it is less active and less effective.29 Finally, a subgroup analysis of older patients with NSCLC who were enrolled in a randomized phase III clinical trial also showed that the combination of gemcitabine and carboplatin at standard doses is feasible, but more toxic, in elderly patients; within this subgroup, there was no statistically significant survival advantage for the combination of carboplatin plus gemcitabine compared with gemcitabine alone.30 In our study, formal comparisons for activity and toxicity between the two treatment groups were not possible because of the nonrandomized design. The decision to consider the platinum and gemcitabine combination as the challenger for future phase III trials is based on the good tolerability and the high activity of this schedule and on the consideration that within a "pick-the-winner" strategy, this combination would be preferred. In addition, although the assumption that higher doses of cisplatin enhance efficacy in advanced NSCLC has never been confirmed, choosing the combination that allows a dose of cisplatin closer to that commonly used as standard should make the planning of a subsequent phase III trial stronger. In conclusion, these MILES-2P studies defined the recommended doses of cisplatin to combine with gemcitabine or vinorelbine in the treatment of elderly patients with advanced NSCLC, and they demonstrated that such combinations are both feasible and active. In particular, the combination of cisplatin and gemcitabine, which provides a higher dose of cisplatin, is considered the best candidate for a phase III trial versus single-agent chemotherapy in the treatment of advanced NSCLC in the elderly population.
Although all authors completed the disclosure declaration, the following authors or their immediate family members indicated a financial interest. No conflict exists for drugs or devices used in a study if they are not being evaluated as part of the investigation. For a detailed description of the disclosure categories, or for more information about ASCO's conflict of interest policy, please refer to the Author Disclosure Declaration and the Disclosures of Potential Conflicts of Interest section in Information for Contributors. Employment or Leadership Position: None Consultant or Advisory Role: Cesare Gridelli, Eli Lilly (C) Stock Ownership: None Honoraria: Cesare Gridelli, Eli Lilly, Glaxo-Wellcome Research Funding: None Expert Testimony: None Other Remuneration: None
Conception and design: Cesare Gridelli, Ciro Gallo, Francesco Perrone Provision of study materials or patients: Cesare Gridelli, Paolo Maione, Alfonso Illiano, Franco Vito Piantedosi, Adolfo Favaretto, Alessandra Bearz, Sergio Federico Robbiati, Virginio Filipazzi, Vito Lorusso, Francesco Carrozza, Rosario Vincenzo Iaffaioli, Luigi Manzione Collection and assembly of data: Cesare Gridelli, Paolo Maione, Alfonso Illiano, Franco Vito Piantedosi, Adolfo Favaretto, Alessandra Bearz, Sergio Federico Robbiati, Virginio Filipazzi, Vito Lorusso, Francesco Carrozza, Rosario Vincenzo Iaffaioli, Luigi Manzione, Alessandro Morabito, Francesco Perrone Data analysis and interpretation: Cesare Gridelli, Paolo Maione, Ciro Gallo, Alessandro Morabito, Francesco Perrone Manuscript writing: Cesare Gridelli, Paolo Maione, Ciro Gallo, Alessandro Morabito, Francesco Perrone Final approval of manuscript: Cesare Gridelli, Paolo Maione, Alfonso Illiano, Franco Vito Piantedosi, Adolfo Favaretto, Alessandra Bearz, Sergio Federico Robbiati, Virginio Filipazzi, Vito Lorusso, Francesco Carrozza, Rosario Vincenzo Iaffaioli, Luigi Manzione, Ciro Gallo, Alessandro Morabito, Francesco Perrone
MILES Investigators who participated in this study: Cesare Gridelli, Paolo Maione, Antonio Rossi (S. Giuseppe Moscati Hospital, Avellino); Francesco Perrone, Alessandro Morabito, Massimo Di Maio, 1 Ermelinda De Maio, 2 Gianfranco De Feo, Jane Bryce, Maria Carmela Piccirillo (National Cancer Institute, Napoli); Ciro Gallo, Giuseppe Signoriello, Paolo Chiodini (Second University, Napoli); Alfonso Illiano, Ciro Battiloro, Danilo Rocco (Monaldi Hospital, Napoli); Francovito Piantedosi, Marina Gilli, Francesca Caputo (Monaldi Hospital, Napoli); Adolfo Favaretto, Cristina Magro, Alessia Compostella (Istituto Oncologico Veneto, Padova); Alessandra Bearz, Simon Spazzapan, Umberto Tirelli (National Cancer Institute, Aviano - PN); Sergio Federico Robbiati, 3 Mirella Sannicolò (Civil Hospital, Rovereto - TN); Virginio Filipazzi, Elena Piazza, Anna Gambaro (L. Sacco Hospital, Milano); Vito Lorusso, 4 Marianna Gianpaglia, 5 Andrea Misino (Oncologic Institute, Bari); Francesco Carrozza, Sante Romito, Gianfranco Giglio (A. Cardarelli Hospital, Campobasso); Rosario Vincenzo Iaffaioli, Gaetano Facchini, Guglielmo Nasti (National Cancer Institute, Naples); Luigi Manzione, Domenico Germano, Domenico Bilancia (S. Carlo Hospital, Potenza); Domenico Galetta, Giuseppe Colucci (Oncologic Institute Bari); Nicola Gebbia, Maria Rosaria Valerio (Policlinico Giaccone - Palermo); Luigi Brancaccio, Brunello Valentino (Monaldi Hospital, Napoli); Luciano Isa, Raffaele Venezia (Serbelloni Hospital, Gorgonzola –MI); Matteo Antonio Capuano, Stefania Quitadamo (Ospedali Riuniti, Foggia); Sandro Barni, Marina Cazzaniga (Civil Hospital, Treviglio –BG); Giuseppe Nettis, Annamaria Anzelmo (Miulli Hospital, Acquaviva delle Fonti –BA); Fortunato Ciardiello, Katia Monaco (Second University, Napoli); Nicolò Borsellino, Giovanni Mangano (Buccheri La Ferla Hospital, Palermo); Cosimo Sacco, Gianpiero Fasola (University of Udine Hospital, Udine); Santi Barbera, Antonio Volpintesta (Mariano Santo Hospital, Cosenza); Claudio Verusio, Raffaella Morena (Civil Hospital, Saronno –VA); Francesco Rosetti, Orazio Vinante (U.L.S.S. 13, Noale –VE); Maria Vittoria Oletti, Alfredo Celano (S. Giovanni Antica Hospital, Torino); Paolo Foa (San Paolo Hospital, Milano); Vittorina Zagonel (Fatebenefratelli Hospital S. Giovanni Calibita, Roma); Fausto Meriggi (Casa di Cura Poliambulanza, Brescia); Annamaria Libroia (Umberto I° Hospital, Nocera Inferiore –SA); Sergio Fava (Civil Hospital, Legnano –MI); Benedetto Rho (S. Corona Hospital, Garbagnate Milanese –MI); Antonio Febbraro (Fatebenefratelli Hospital, Benevento); Massimo Rinaldi (Regina Elena Institute –Roma); Italy. Present addresses: 1Civil Hospital, Rossano –CS; 2Alta Valdelsa Hospital, Siena, Italy; 3Alto Garda and Ledro Hospital, Arco –TN; 4Vito Fazzi Hospital, Lecce; 5Policlinico, University of Bari.
We thank the study participants; Federika Crudele, Giuliana Canzanella, Fiorella Romano, and Giovanni de Matteis for data management; and Alfonso Savio for informatic support.
The Clinical Trials Unit of the National Cancer Institute, Naples is supported in part by the nonprofit group Associazione Italiana per la Ricerca sul Cancro. Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.
1. Parkin DM: Global cancer statistics in the year 2000. Lancet Oncol 2:533-543, 2001[CrossRef][Medline] 2. Survelliance, Epidemiology, and End Results (SEER): Cancer Statistics Review 1975-2004, National Cancer Institute. Bethesda, MD. http://www.seer.cancer.gov/csr/1975_2004/ 3. The Elderly Lung Cancer Vinorelbine Italian Study Group: Effects of vinorelbine on quality of life and survival of elderly patients with advanced non small cell lung cancer. J Natl Cancer Inst 91:66-72, 1999 4. Gridelli C, Perrone F, Gallo C, et al: 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. J Natl Cancer Inst 95:362-372, 2003 5. Gridelli C, Aapro M, Ardizzoni A, et al: Treatment of advanced non-small-cell lung cancer in the elderly: Results of an International Expert Panel. J Clin Oncol 23:3125-3137, 2005 6. Pfister DG, Johnson DH, Azzoli CG, et al: American Society of Clinical Oncology treatment of unresectable non-small-cell lung cancer guideline: Update 2003. J Clin Oncol 22:330-353, 2004 7. Minami H, Ohe Y, Niho S, et al: Comparison of pharmacokinetics and pharmacodynamics of docetaxel and cisplatin in elderly and non-elderly patients: Why is toxicity increased in elderly patients? J Clin Oncol 22:2901-2908, 2004 8. Langer CJ, Manola J, Bernardo P, et al: Cisplatin-based therapy for elderly patients with advanced non-small-cell lung cancer: Implications of Eastern Cooperative Oncology Group 5592, a randomized trial. J Natl Cancer Inst 94:173-181, 2002 9. Kubota K, Furuse K, Kawahara M, et al: Cisplatin-based combination chemotherapy for elderly patients with non-small-cell lung cancer. Cancer Chemother Pharmacol 40:469-474, 1997[CrossRef][Medline] 10. Chen TT, Tie-Hua NG: Optimal flexible designs in phase II clinical trials. Stat Med 17:2301-2312, 1998[CrossRef][Medline] 11. Langer CJ, Vangel M, Schiller J, et al: Age-specific subanalysis of ECOG 1594: fit elderly patients (70-80 yrs) with NSCLC do as well as younger pts (< 70). Proc Am Soc Clin Oncol 22:639, 2003 (abstr 2571) 12. Kelly K, Giarritta S, Hayes S, et al: Should older patients receive combination chemotherapy for advanced stage non-small cell lung cancer? An analysis of Southwest Oncology trials 9509 and 9308. Proc Am Soc Clin Oncol 20:329a, 2001 (abstr 1313) 13. Belani CP, Fossella F: Elderly subgroup analysis of a randomized phase III study of docetaxel plus platinum combinations versus vinorelbine plus cisplatin for first-line treatment of advanced nonsmall cell lung carcinoma (TAX 326). Cancer 104:2766-2774, 2005[CrossRef][Medline] 14. Lilenbaum RC, Herndon JE, List M, et al: Single-agent versus combination chemotherapy in advanced non-small cell lung cancer: A CALGB randomized trial of efficacy, quality of life, and cost-effectiveness. J Clin Oncol 23:190-196, 2005 15. Hensing TA, Peterman AH, Schell MJ, et al: The impact of age on toxicity, response rate, quality of life, and survival in patients with advanced, stage IIIB or IV non small cell lung carcinoma treated with carboplatin and paclitaxel. Cancer 98:779-788, 2003[CrossRef][Medline] 16. Ramalingam S, Barstis J, Perry MC, et al: Treatment of elderly non-small cell lung cancer patients with three different schedules of weekly paclitaxel in combination with carboplatin: Subanalysis of a randomized trial. J Thorac Oncol 1:240-244, 2006[Medline] 17. Perrone F, Gallo C, Gridelli C: Re: Cisplatin-based therapy for elderly patients with advanced non-small cell lung cancer: Implications of Eastern Cooperative Oncology Group 5592, a randomized trial. J Natl Cancer Inst 94:1029-1030, 2002 18. Jatoi A, Hillman S, Stella P, et al: Should elderly non-small-cell lung cancer patients be offered elderly-specific trials? Results of a pooled analysis from the north Central Cancer Treatment Group. J Clin Oncol 23:9113-9119, 2005 19. Ohe Y, Niho S, Kakinuma R, et al: A phase II study of cisplatin and docetaxel administered as three consecutive weekly infusions for advanced non-small cell lung cancer in elderly patients. Ann Oncol 15:45-50, 2004 20. Maestu IC, Gomez-Aldaravì L, Torregrossa MD, et al: Gemcitabine and low dose carboplatin in the treatment of elderly patients with advanced non-small cell lung cancer. Lung Cancer 42:345-354, 2003[CrossRef][Medline] 21. Okamoto I, Moriyama E, Kishi H, et al: Multicenter phase II study of the combination of carboplatin and paclitaxel as first line treatment in elderly patients with advanced non small cell lung cancer. Proc Am Soc Clin Oncol 23:672, 2004 (abstr 7239) 22. Choi IS, Kim BS, Park SR, et al: Efficacy of modified regimen with attenuated doses of paclitaxel plus carboplatin combination chemotherapy in elderly and/or weak patients with advanced non small cell lung cancer. Lung Cancer 39:99-101, 2003[CrossRef][Medline] 23. Molinier O, Milleron B, Breton JL, et al: Multicenter phase II trial of carboplatin and weekly pacitaxel as first-line treatment in elderly patients with non small cell lung cancer: Preliminary results. Proc Am Soc Clin Oncol 22:693, 2003 (abstr 2786) 24. Inoue A, Usui, K, Ishimoto O, et al: A phase II study of weekly paclitaxel combined with carboplatin for elderly patients with advanced non-small cell lung cancer. Lung Cancer 52:83-87, 2006[CrossRef][Medline] 25. Takatani H, Kinoshita A, Fukuda M, et al: A phase II study of vinoreline (VNR) and carboplatin (CBDCA) in elderly patients (pts) with advanced non-small cell lung cancer (NSCLC). J Clin Oncol 24:18S, 2006 (abstr 17108)[CrossRef] 26. Tsukada H, Yokoyama A, Nishiwaki Y, et al: Randomized controlled trial comparing docetaxel (D)-cisplatin (P) combination with D alone in elderly patients (pts) with advanced non-small cell lung cancer (NSCLC): JCOC0207. J Clin Oncol 25:18S, 2007 (7629 abstr) 27. Feliu J, Martin G, Madronal C, et al: Combination of low-dose cisplatin and gemcitabine for treatment of elderly patients with advanced non small cell lung cancer. Cancer Chemother Pharmacol 52:247-252, 2003[CrossRef][Medline] 28. Berardi R, Porfiri E, Scartozzi M, et al: Elderly patients with advanced non-small cell lung cancer: A phase II study with weekly cisplatin and gemcitabine. Oncology 65:198-203, 2003[CrossRef][Medline] 29. Shepherd FA, Abratt R, Crinò L, et al: The influence of gemcitabine and cisplatin schedule on response and survival in advanced non small cell lung cancer. Lung Cancer 30:117-125, 2000[CrossRef][Medline] 30. Sederholm C, Hillerdal G, Lamberg K, et al: Phase III trial of gemcitabine plus carboplatin versus single-agent gemcitabine in the treatment of locally advanced or metastatic non-small-cell lung cancer: The Swedish lung cancer study group. J Clin Oncol 23:8380-8388, 2005 Submitted May 14, 2007; accepted July 17, 2007.
This article has been cited by other articles:
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||||||||||
|
|||||||||||
|
|
Copyright © 2007 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
|
TOP
ABSTRACT
INTRODUCTION
2,000/µL, platelets 
