© 2002 by Oxford University Press
Journal of the National Cancer Institute, Vol. 94, No. 13, 1029-1030,
July 3, 2002
© 2002 Oxford University Press
CORRESPONDENCE |
Re: Cisplatin-Based Therapy for Elderly Patients With Advanced Non-Small-Cell Lung Cancer: Implications of Eastern Cooperative Oncology Group 5592, a Randomized Trial
Affiliations of authors: F. Perrone, Clinical Trials Unit, National Cancer Institute (NCI), Naples, Italy; C. Gallo, Medical Statistics, Second University of Naples, Naples, Italy; C. Gridelli, Medical Oncology, S. Giuseppe Moscati Hospital, Avellino, Italy. All authors are members of the Clinical Trials Promoting Group (CTPG)–Lung Cancer Section.
Correspondence to: F. Perrone, M.D., Ph.D., Clinical Trials Unit, NCI, via M. Semmola, 80131 Naples, Italy (e-mail: fr.perrone{at}agora.it).
A recent report by Langer et al. (1) in the Journal suggests that cisplatin-based therapy for treatment of advanced non-small-cell lung cancer (NSCLC) should not be denied to fit elderly patients. Their conclusion is based on a retrospective analysis of the Eastern Cooperative Oncology Group (ECOG) 5592 phase III randomized trial of three cisplatin-based regimens, which showed that outcomes did not differ between adult patients younger than 70 years of age and elderly patients 70 years of age or older, i.e., 84 septuagenarians and two octogenarians (15% of the study population).
However, we believe that the generalizability of these results is poor because of possible selection bias and because nowadays there is no evidence that "elderly do as well (or as poorly) as younger patients" as stated by Langer et al. (1). With regard to selection bias, Langer et al. acknowledge that the percentage of elderly patients among patients diagnosed with lung cancer in clinical practice is much higher than the percentage of elderly patients among patients enrolled in clinical trials for lung cancer treatment (2). It is predictable that eligibility criteria for participation in clinical trials become more stringent when increasingly toxic treatments are involved. In addition, further selection bias can occur when physicians attempt to recruit particularly well performing patients. Without such biases, elderly patients would not be underrepresented in U.S. clinical trials.
We suspect that selection biases are more of a problem in retrospective studies, in which age–treatment interactions are derived from a substantially younger population, than in prospective studies focused specifically on the elderly; we agree, therefore, with Langer et al. that there is a "need for elderly-specific trials" (1). In the ECOG 5592 study, the proportion of elderly patients was less than half of what would have been expected on the basis of population data (2). In two recent trials of chemotherapy for NSCLC (ELVIS and MILES) (3,4), we enrolled elderly patients by using selection criteria similar to those used in the ECOG 5592 trial but with a lower age limit (70 years). In the same time period, we also ran two trials (GemVin phase 1–2 and GemVin phase 3) with adult patients (Fig. 1
), again with similar selection criteria (5,6). Forty-five of the 115 Italian centers participating in these trials enrolled subjects in both the elderly and adult studies, with 960 patients randomly assigned overall—455 (47%) adult and 505 (53%) elderly—from February 1997 through October 2000. Clearly, representation of elderly patients is much higher in these trials than in the ECOG 5592 trial and, we suspect, than in all clinical trials ever conducted on chemotherapy for advanced NSCLC. An important finding of our trials of chemotherapy dedicated to elderly NSCLC patients (3,4) is that single-agent chemotherapy with vinorelbine or gemcitabine, without cisplatin, is an appropriate NSCLC treatment for elderly patients. Similar evidence is still lacking for cisplatin-based chemotherapy.
|
The selection biases affecting the retrospective study by Langer et al. mean that great caution is needed in the interpretation of their data. On one hand, their conclusion might be of value only for a small proportion of elderly patients, but there is no reliable method available to select these patients from the elderly population as a whole. On the other hand, and more important, if the data reported by Langer et al. (1) were to stimulate the use of cisplatin-based chemotherapy in elderly patients, many elderly patients could potentially be put at risk because no prospective trial has yet shown that cisplatin is safe in the elderly.
We agree that cisplatin combinations should be tested in elderly patients, with the goal of improving results obtained with single-agent treatments. However, safety issues should be addressed, and the use of lower, tailored doses of treatment regimens that are thought to be effective (7) should be tested in prospective studies before evaluation in large randomized clinical trials.
NOTES
Editor's note: F. Perrone and C. Gallo have obtained honoraria from GlaxoSmithKline (Verona, Italy) for editorial activities. F. Perrone is a member of a study steering committee for AstraZeneca (Milan, Italy). C. Gridelli is a member of the speaker's bureau for Eli Lilly (Firenze, Italy), Pierre-Fabre (Genevois, France), GlaxoSmithKline (Research Triangle Park, NC), Aventis Pharmaceuticals (Milan), AstraZeneca, and Roche (Basel, Switzerland). C. Gridelli is currently conducting a clinical trial sponsored by AstraZeneca.
REFERENCES
1
Langer CJ, Manola J, Bernardo P, Kugler JW, Bonomi P, Cella D, 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 2002;94:173–81.
2
Hutchins LF, Unger JM, Crowley JJ, Coltman CA Jr, Albain KS. Underrepresentation of patients 65 years of age or older in cancer-treatment trials. N Engl J Med 1999;341:2061–7.
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 1999;91: 66–72.
4 Gridelli C, Perrone F, Cigolari S, Manzione L, Piantedosi F, Barbera S, et al. The MILES (Multicenter Italian Lung Cancer in the Elderly Study) phase III trial: gemcitabine and vinorelbine vs. vinorelbine and vs. gemcitabine in elderly advanced non-small cell lung cancer. Proc ASCO 2001;20:308a.
5 Gridelli C, Frontini L, Perrone F, Gallo C, Gulisano M, Cigolari S, et al. Gemcitabine plus Vinorelbine in advanced non-small cell lung cancer: a phase II study of three different doses. Gem Vin Investigators. Br J Cancer 2000;83:707–14.[CrossRef][Web of Science][Medline]
6 Gridelli C, Shepherd F, Perrone F, Illiano A, Piantedosi FV, Robbiati SF, et al. GEMVIN III: a phase III study of gemcitabine plus vinorelbine (GV) compared to cisplatin plus vinorelbine or gemcitabine chemotherapy (PCT) for stage IIIB or IV non-small cell lung cancer (NSCLC): an Italo-Canadian study. Proc ASCO 2002;21:292a.
7 Ellis PA, Smith IE, Hardy JR, Nicolson MC, Talbot DC, Ashley SE, et al. Symptom relief with MVP (mitomycin C, vinblastine and cisplatin) chemotherapy in advanced non-small-cell lung cancer. Br J Cancer 1995;71:366–70.[Web of Science][Medline]
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  C. Gridelli, P. Maione, and A. Rossi Chemotherapy and Targeted Therapy for Older Patients with Advanced Non-small Cell Lung Cancer ASCO Educational Book, January 1, 2009; 2009(1): 283 - 287. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Gridelli Treatment of Advanced Non Small-Cell Lung Cancer in the Elderly: From Best Supportive Care to the Combination of Platin-Based Chemotherapy and Targeted Therapies J. Clin. Oncol., January 1, 2008; 26(1): 13 - 15. [Full Text] [PDF]
|
|
|
|
|
|
C. Gridelli, P. Maione, A. Illiano, F. V. Piantedosi, A. Favaretto, A. Bearz, S. F. Robbiati, V. Filipazzi, V. Lorusso, F. Carrozza, et al. Cisplatin Plus Gemcitabine or Vinorelbine for Elderly Patients With Advanced Non Small-Cell Lung Cancer: The MILES-2P Studies J. Clin. Oncol., October 10, 2007; 25(29): 4663 - 4669. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Gridelli, C. Langer, P. Maione, A. Rossi, and S. E. Schild Lung Cancer in the Elderly J. Clin. Oncol., May 10, 2007; 25(14): 1898 - 1907. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Maione, F. Perrone, C. Gallo, L. Manzione, F. Piantedosi, S. Barbera, S. Cigolari, F. Rosetti, E. Piazza, S. F. Robbiati, et al. Pretreatment Quality of Life and Functional Status Assessment Significantly Predict Survival of Elderly Patients With Advanced Non--Small-Cell Lung Cancer Receiving Chemotherapy: A Prognostic Analysis of the Multicenter Italian Lung Cancer in the Elderly Study J. Clin. Oncol., October 1, 2005; 23(28): 6865 - 6872. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Gridelli and F. A. Shepherd Chemotherapy for Elderly Patients With Non-Small Cell Lung Cancer: A Review of the Evidence Chest, August 1, 2005; 128(2): 947 - 957. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Rossi, P. Maione, G. Colantuoni, C. Guerriero, C. Ferrara, F. Del Gaizo, D. Nicolella, and C. Gridelli Treatment of Small Cell Lung Cancer in the Elderly Oncologist, June 1, 2005; 10(6): 399 - 411. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Gridelli, M. Aapro, A. Ardizzoni, L. Balducci, F. De Marinis, K. Kelly, T. Le Chevalier, C. Manegold, F. Perrone, R. Rosell, et al. Treatment of Advanced Non-Small-Cell Lung Cancer in the Elderly: Results of an International Expert Panel J. Clin. Oncol., May 1, 2005; 23(13): 3125 - 3137. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. D. Makrantonakis, E. Galani, and P. G. Harper Non-Small Cell Lung Cancer in the Elderly Oncologist, September 1, 2004; 9(5): 556 - 560. [Abstract] [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]
|
|
|
|
 |
|
 C. Gridelli, F. Perrone, C. Gallo, S. Cigolari, A. Rossi, F. Piantedosi, S. Barbera, F. Ferrau, E. Piazza, F. Rosetti, 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, March 5, 2003; 95(5): 362 - 372. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||