To the Editor:

The recently published 2003 update of the American Society of Clinical Oncology treatment of unresectable non–small-cell lung cancer guidelines¹ explicitly recalled our attention to the fact that, in the primary report of the Multicenter Italian Lung Cancer in the Elderly Study (MILES) trial,² according to the study plan, we did not perform subgroup analyses based on performance status (PS). The MILES trial compared polychemotherapy with vinorelbine plus gemcitabine (GEMVIN) versus single-agent chemotherapy with vinorelbine or gemcitabine in advanced non–small-cell lung cancer patients older than 70 years and found that the combination was not better than both single agents for all efficacy outcomes, including survival (primary end point), time to progression, response rate, and quality of life. In addition, the combination was more toxic than single agents. MILES randomization was stratified by PS, thus we are able to give here more information on PS 2 patients.

Of 698 patients enrolled and analyzed in the MILES study, 130 (18.6%) were classified as PS 2 at randomization. Baseline characteristics by PS are listed in Table 1. PS 2 patients tended to have more sites involved by cancer (P = .008) and a higher incidence of comorbidity (P = .04), namely of the respiratory tract (P = .025). Activities of Daily Living and Instrumental Activities of Daily Living scale scores were significantly worse among PS 2 patients (P < .0001 and P = .0002, respectively). Treatments were well balanced within PS categories.

Study outcomes scattered by treatment arms and PS categories are listed in Table 2. PS 2 patients received a lowernumber of cycles than patients with PS 0 to 1 (mean, 3.12 v 4.1 cycles; median, 3 v 4 cycles; P < .001). Incidence and severity of toxicity did not dramatically differ among PS categories, but the overall lower amount of drugs administered in PS 2 patients should be considered in the interpretation of this point. The pattern of toxicity, both hematologic and nonhematologic, scattered by treatment arms did not significantly vary according to PS categories.

All efficacy outcomes (survival, time to progression, and response rate) were consistently worse for PS 2 versus PS 0 to 1 patients (Table 2). When combination treatment was compared with single agents, no significant difference was found for any outcome. Survival curves of treatments scattered by PS are depicted in Figure 1. Testing the interaction between PS and treatments on survival in a Cox regression model, adjusting by size of center, age, sex, stage, histotype, and major comorbidities, still yielded results that were not significant (P = .35 for GEMVIN v vinorelbine and P = .34 for GEMVIN v gemcitabine).

View larger version:

• In this window
• In a new window

• PowerPoint Slide for Teaching

Fig 1.

Overall survival by treatment arms within performance status 0 to 1 (top) and performance status 2 (bottom) patients. Solid line represents vinorelbine, dotted line represents gemcitabine, and dashed line represents combination.

These data confirm the lack of effectiveness of combination chemotherapy with gemcitabine and vinorelbine versus each single agent in the subgroup of PS 2 patients. All treatments studied were substantially well tolerated in PS 2 patients as well as in PS 0 to 1 patients; however, the overall survival was significantly shorter in PS 2 patients. In our opinion, this is a further warning regarding the role of chemotherapy and the need of new therapeutic strategies for unfit patients.³ At present, single-agent chemotherapy with drugs characterized by a low toxicity profile should remain the standard treatment for PS 2 patients.⁴ Consequently, single-agent chemotherapy should be the standard arm against which experimental treatments should be tested in randomized clinical trials dedicated to PS 2 patients.

Authors' Disclosures of Potential Conflicts of Interest

The following authors or their immediate family members have 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. Consultant/Advisory Role: Cesare Gridelli, Eli Lilly. Honoraria: Cesare Gridelli: Eli Lilly, Pierre Fabre. For a detailed description of these 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 of Information for Contributors found in the front of every issue.