Toward Developing a Rational Strategy for Advanced Lung Cancer Treatment in the Elderly

Abstract & Commentary

Synopsis: In a multicenter, Italian, randomized, phase III trial, single-agent vinorelbine or gemcitabine proved to be as effective as a combination of the 2 agents in the treatment of advanced non-small-cell lung cancer occurring in patients 70 years and older. For the most part, toxicity was less with single-agent therapy (vinorelbine or gemcitabine) compared with the combination, but indicators of quality of life were comparable in all 3 treatment arms.

Source: Gridelli C, et al. J Natl Cancer Inst. 2003;95: 362-372.

Lung cancer occurs commonly in elderly patients, many of whom have significant comorbidities that might preclude effective antineoplastic therapy. Yet in a prior study,1 this Italian group demonstrated that elderly patients treated with single-agent vinorelbine had improved overall survival (median of 28 vs 21 weeks) and scored better on certain measures of quality of life, when compared to patients who were treated with supportive care alone (without antineoplastic drug). In the current study, the combination of vinorelbine plus gemcitabine was compared to either agent administered alone in elderly patients with advanced lung cancer.

Patients aged 70 years and older were randomly assigned to receive intravenous vinorelbine (30 mg/m2), gemcitabine (1200 mg/m2), or vinorelbine (25 mg/m2) plus gemcitabine (1000 mg/m2). All treatments were delivered on days 1 and 8 every 3 weeks for a maximum of 6 cycles. The primary end point was survival and secondary outcomes were quality of life and toxicity.

Of 698 patients available for intention-to-treat analysis, 233 were assigned to receive vinorelbine, 233 to gemcitabine, and 232 to vinorelbine plus gemcitabine. Compared with each single drug, the combination treatment did not improve survival. The hazard ratio of death for patients receiving the combination treatment was 1.17 (95% confidence interval [CI], 0.95-1.44) that of patients receiving vinorelbine, and 1.06 (95% CI, 0.86-1.29) that of patients receiving the gemcitabine. Although quality of life was similar across the 3 treatment arms, the combination treatment was more toxic than the 2 drugs given singly.

Gridelli and associates concluded that the combination of vinorelbine plus gemcitabine is not more effective than single-agent vinorelbine or gemcitabine in the treatment of advanced non-small-cell lung cancer in elderly patients.

Comment by William B. Ershler, MD

The median age of newly diagnosed lung cancer is approximately 68 years, and as many as 40% may be older than 70 years at diagnosis.2 For younger adults with advanced disease, cisplatin-based chemotherapy regimens have become standard management,3 but there has long been concern that older patients, particularly those with significant comorbidities, would experience unacceptable toxicities with these aggressive regimens. Thus, until recently, it was common practice to exclude older lung cancer patients from chemotherapeutic intervention.

In 1999, the Elderly Lung Cancer Vinorelbine Italian Study (ELVIS) was published demonstrating that single-agent vinorelbine was superior to best supportive care in both survival and quality of life. The MILES study was designed to test the hypothesis that the combination of vinorelbine with gemcitabine would be better than either agent alone. The rationale for this conjecture was that drugs have been shown to be active in non-small-cell cancer, both are well tolerated by older patients,1,4 and each has a distinct mechanism of action. However, the results did not show benefit for the combination in terms of survival, and, although quality of life was similar across all 3 treatment arms, the combination treatment was more toxic that the 2 drugs given singly. The study wasn’t designed to compare vinorelbine and gemcitabine as single agents, but it appears that they are comparable with regard to efficacy and toxicity. Future studies, no doubt, will compare other agents, such as the taxanes, or Iressa, either alone or in combination. However, until new data are available, single-agent vinorelbine or gemcitabine may well be considered standard of care for elderly patients with advanced non-small-cell lung cancer.

The Italian investigators who brought us ELVIS and now MILES should be commended for their groundbreaking work in geriatric oncology. These studies incorporated many of the factors determined to be relevant in geriatric medicine, including a pretreatment geriatric assessment and outcomes that included a determination of quality of life. There is now an increasing awareness that close to 50% of cancer occurs in patients older than age 65. Trials that focus on management in typical patients who are likely to have comorbidities and various functional impairments will be of increasing importance in the decades to come.

Dr. Ershler, INOVA Fairfax Hospital Cancer Center, Fairfax, VA; Director, Institute for Advanced Studies in Aging, Washington, DC.


1. Elderly Lung Cancer Vinorelbine Italian Study Group. J Natl Cancer Inst. 1999;91:66-72.

2. Earle CC, et al. Chest. 2000;117:1239-1246.

3. Non-Small Cell Lung Cancer Collaborative Group BMJ. 1995;311:899-909.

4. Shepard FA, et al. Semin Oncol. 1997;24 (2 Suppl 7):50-55.