CORRESPONDENCE

RESPONSE: Re: Cisplatin-Based Therapy for Elderly Patients With Advanced Non-Small-Cell Lung Cancer: Implications of Eastern Cooperative Oncology Group 5592, a Randomized Trial

Corey J. Langer, David H. Johnson

Affiliations of authors: C. J. Langer, Fox Chase Cancer Center, Philadelphia, PA; D. H. Johnson, Vanderbilt-Ingram Cancer Center, Nashville, TN.

Correspondence to: Corey J. Langer, M.D., Fox Chase Cancer Center, Department of Medical Oncology, 7701 Burholme Ave., Philadelphia, PA 19111 (e-mail: CJ_Langer{at}fccc.edu).

We appreciate the comments of Perrone et al., who raise the specter of selection bias and, as evidence, cite the disproportionate underenrollment of elderly patients in the Eastern Cooperative Oncology Group (ECOG) 5592 trial (1) and in other efforts (2). They contend that oncologists preferentially recruit particularly well performing patients and that such individuals are not representative of the elderly population at large. Unfortunately, in the context of a North American cooperative group trial, it is virtually impossible to track all potential enrollees and to delineate the reasons that patients who are screened for a particular study are ultimately not enrolled. There are two possible reasons for underrepresentation of the elderly in the ECOG 5592 trial: 1) A higher incidence of comorbidities and compromised performance status was observed in elderly patients, which would have rendered these patients ineligible or marginally eligible. 2) There was selection bias against including elderly patients in platinum-based chemotherapy trials because of the perceived unsuitability of these patients for platinum-based therapy and the potential increased risk of life-threatening toxicity.

Gridelli and colleagues have blazed the path for elderly-specific research in non-small-cell lung cancer (NSCLC). Their studies have shown that single-agent therapy with vinorelbine has a positive impact on survival and quality of life (QOL) compared with supportive care (3), and non-platinum combination therapy with gemcitabine and vinorelbine appears to be no better than the constituent single-agent therapies (4). To date, however, no elderly-specific study in NSCLC has compared a single-agent therapy to a combination of that agent with platinum, either carboplatin or cisplatin. The randomized phase III Cancer and Leukemia Group B (CALGB) trial comparing paclitaxel alone with paclitaxel in combination with carboplatin, reported at this year's (2002) annual meeting of the American Society of Clinical Oncology (ASCO) (5), demonstrated that both older (>=70 years) and younger patients receiving combination carboplatin and paclitaxel fared better than those patients who received single-agent paclitaxel alone; they had statistically significantly higher response rates, better time to progression, and statistically significantly increased median survival. However, it should be noted that the CALGB trial was not designed specifically for the elderly.

Three other points must also be made with regard to the treatment of elderly patients diagnosed with NSCLC: 1) We need to assess the comorbidities of elderly patients prospectively, and we need to determine the influence of comorbidity on drug toxicity, survival, and QOL, particularly because other medical illnesses, within a specific performance status category, may have substantial influence on each of these study end points. 2) We need to design clinical trials that include fit octogenarians; they are virtually invisible in current trials. 3) We need to take great care in both the choice of platinum-containing chemotherapy regimens in the elderly and in the choice of dosages.

To this end, a retrospective secondary analysis by Kelly et al. (6) of the Southwest Oncology Group trials 9308 and 9509, which compared a combination of cisplatin and vinorelbine, first to cisplatin alone and then to a combination of paclitaxel and carboplatin, indicated that a substantially higher percentage of elderly patients who were receiving cisplatin plus vinorelbine were taken off the trial because of drug toxicity compared with younger patients (P = .003) (6). No such difference was seen for paclitaxel and carboplatin. In addition, at this year's ASCO annual meeting, Shiller et al. (7), on behalf of ECOG, reviewed the ECOG NSCLC 5592 trial experience from 1980 through 2000. In that time, 3398 patients with no explicit age restrictions were accrued to chemotherapy trials for treatment of NSCLC; a Cox proportional hazards model showed that the decade of diagnosis (i.e., 1980–1990 versus 1990–2000), performance status, and treatment (i.e., platinum-based therapy versus non-platinum-based therapy) all had a statistically significant impact on survival, whereas age did not (7).

Even as our understanding of NSCLC matures, cancer in the elderly remains a challenging frontier of therapeutic oncology. We should not fear its exploration.

NOTES

Editor's Note: C. J. Langer is a member of the speakers' bureau for Bristol-Myers Squibb.

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.[Abstract/Free Full Text]

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.[Abstract/Free Full Text]

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.[Abstract/Free Full Text]

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 Lillenbaum RC, Herndon J, List M, Desch C, Watson D, Holland J, et al. Single agent versus combination chemotherapy in advanced NSCLC: a CALGB randomized trial of efficacy, quality of life (QOL), and cost-effectiveness. Proc ASCO 2002;21:1a.

6 Kelly K, Giarritta S, Hayes S, Akerley W, Hesketh P, Wozniak A, et al. Should older patients receive combination chemotherapy for advanced non-small cell lung cancer (NSCLC)? An analysis of Southwest Oncology Trials 9509 and 9308. Proc ASCO 2001;20:329a.

7 Schiller JH, Bernado P, Harrington D, Johnson H. Comparison of outcome and patient characteristics in advanced non-small cell lung cancer (NSCLC): analysis of Eastern Cooperative Oncology Group trials from 1980– 2000. Proc ASCO 2002;21:304a.



             
Copyright © 2002 Oxford University Press (unless otherwise stated)
Oxford University Press Privacy Policy and Legal Statement