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Choosing the Right Chemotherapy for Elderly NSCL Cancer Patients
Abstract & Commentary
Synopsis: The current report examines the importance of patient age with regard to toxicity and response rates when treated with carboplatin and paclitaxel for advanced lung cancer. Similar toxicity profiles were observed in those younger or older than 70 years of age, and response rates were also similar.
Source: Hensing TA, et al. Cancer. 2003;98: 779-788.
There remains controversy about the optimal treatment for patients with lung cancer who are older than 70 years. In a previously reported1 phase-III trial with no age restriction, the duration of therapy with carboplatin and paclitaxel was compared for patients with stage IIIB or IV non-small-cell lung cancer. The findings indicated that there was no difference in survival or in quality of life when treatment was extended beyond 4 cycles. The current report re-examines these data set in the context of patient age. Of the 230 patients who were subjects of the earlier report, 67 were 70 years or older (29%). These patients were compared with those younger than 70 receiving the same treatment regimens. The chemotherapy involved the use of carboplatin at an area under the curve (AUC) of 6 and paclitaxel at a dose of 200 mg/m2 every 21 days. Individuals received either a scheduled 4 cycles of this combination or additional cycles until there was evidence for disease progression. As it turns out, the median number of cycles delivered for both age groups was 4 cycles (range, 0-19 cycles). There were no statistically significant differences in any of the most common toxicities observed in patients younger than age 70 years compared with patients age 70 years and older. This included neutropenia (38% vs 35%), neuropathy (13% vs 16%), myalgia/arthralgia (15% vs 9%), malaise (8% vs 15%), anemia (9% vs 4%), thrombocytopenia (7% vs 9%), anorexia (8% vs 4%), and nausea/emesis (14% vs 15%).
Hensing and colleagues concluded that their analysis demonstrated that carboplatin/paclitaxel exhibited similar toxicity profiles in patients age 70 years and older compared with patients younger than age 70 years. The survival rates were not different between the 2 age groups, and there was no difference in progression or quality-of-life outcomes. Thus, they concluded that in fit, elderly patients carboplatin/paclitaxel combined therapy represented a reasonable standard regimen, inasmuch as no excessive toxicity was observed and efficacy was comparable to younger patients.
Comment by W0illiam B. Ershler, MD
This reports highlights what many practicing oncologists have understood for some time, that older patients who are referred to and eligible for clinical trials using combination chemotherapy regimens are likely to fare generally as well as younger patients. It is encouraging to see some additional solid data that reflect this clinical impression.
The problem, however, comes in the determination of the appropriate patients for combined agent therapy. What remains is a bias with regard to entering elderly patients onto study. Despite concerted efforts at recruitment, the "typical" older patients are disproportionately under-represented in such clinical trials. For example, in the current study only 29% of the patients enrolled were older than age 70, whereas registry data indicate that the median age for incipient lung cancer is approximately 70 years. Thus, although half the patients in the general community with lung cancer are 70 years or older, only approximately a quarter of the current trial fell into this age group. Of course, it may be that older patients prefer not to be on trial because of the logistical problems involved in frequent clinic visits, aggressive testing, etc. Probably more likely, however, is that older patients, by virtue of age-associated comorbidities, are less likely to be eligible for study. Thus, despite the appeal of the current findings, the implications for the "typical" geriatric lung cancer patient remain to be clarified. Certainly, the current report would suggest that physiologically fit older patients should be treated with standard regimens in a manner similar to younger patients.
The issue of what to do with the "typical" geriatric patient who does have comorbidities and a performance score below a Karnofsky of 70 remains to be determined. There have been recent reports, particularly from Italy, indicating the use of single-agent treatment, either vinorelbine or gemcitabine,2,3 suggesting that observed tumor regression and maintained quality of life were better in treated individuals than that compared to those receiving just supportive care. Which single-agent use remains unclear. When vinorelbine was compared directly with gemcitabine for example, responses rates were comparable.3
The optimal treatment for elderly patients with advanced NSCL cancer remains uncertain. The data presented would suggest that the commonly used standard approach of carboplatin and paclitaxel is well tolerated in elderly patients, and certainly this approach is reasonable for those who are fit and without significant comorbidity. Further research is clearly called for with regard to defining the optimal treatment for the typical geriatric lung cancer patient. Use of a somewhat more detailed pretreatment assessment tool and the evaluation of the importance of various comorbidites would seem likely targets for investigation, in the context of either single-agent or combination chemotherapies.
Dr. Ershler is INOVA Fairfax Hospital Cancer Center, Fairfax, VA; Director, Institute for Advanced Studies in Aging, Washington, D.C.
1. Socinski MA, et al. J Clin Oncol. 2002;20:1335-1343.
2. The Elderly Lung Cancer Vinorelbine Italian Study Group. J Natl Cancer Inst. 1999;91:66-72.
3. Gridelli C, et al. J Natl Cancer Inst. 2003;95:362-372.