Vinorelbine for Elderly Patients With Lung Cancer
abstract & commentary
Synopsis: Patients with unresectable nonsmall cell lung cancer older than 70 years of age were randomly assigned to receive supportive care or single-agent vinorelbine on days 1 and 8 of a 21-day cycle. Median survival increased from 21 to 28 weeks in patients treated with vinorelbine (P = 0.03) and the relative hazard of death for vinorelbine-treated patients was 0.65.
Source: The Elderly Lung Cancer Vinorelbine Italian Study Group. J Natl Cancer Inst 1999;91:66-72.
The treatment for lung cancer has not reached the desired level of efficacy. In fact, in many patients, no therapy is offered because of the legitimate concern that treatment does not have a sufficient therapeutic index. The treatment produces toxicity universally and only a small chance for a short extension of survival. A well-known colleague has often referred to the process he goes through with patients as "randomizing them to the Bahamas." Survival extension has been reliably documented mainly with platinum-containing drug regimens1 and these regimens have sufficiently great toxic effects that they are often never considered in old patients.
Vinorelbine is a semisynthetic vinca alkyloid that has impressive phase II activity in lung cancer (23% response rate)2 and was as effective as combined vindesine plus cisplatin in a large randomized trial.3 Therefore, the Elderly Lung Cancer Vinorelbine Italian Study (ELVIS) Group undertook a multicenter prospective randomized trial comparing supportive care with vinorelbine given at 30 mg/m2 IV on days 1 and 8 of a 21-day cycle for six cycles. Eligibility requirements included a histologic diagnosis of nonsmall cell lung cancer, age 70 years or older, ECOG performance status less than 2, and stage IIIB or IV disease. Patients with brain metastases, prior chemotherapy, a prior cancer, or compromised marrow, kidney, or liver function were excluded. Quality-of-life end points were measured with the European Organization for Research and Treatment of Cancer (EORTC) questionnaires QLQ-C30 and QLQ-LC13.
ELVIS investigators terminated the study early because of slow enrollment. They had been aiming to enter 350 patients but stopped the study after 191 patients had been randomly assigned. Of these, 30 had not had sufficient follow-up to evaluate the treatment outcome. Therefore, 161 patients were analyzed, 80 assigned to vinorelbine and 81 to supportive care. Eighty-seven percent of the patients were male, the median age was 74 years, three-fourths had stage IV disease, and four-fifths had ECOG performance status of 1 or greater.
Baseline quality-of-life scores were similar on the two arms. Over time, EORTC functional scales were consistently better for patients receiving vinorelbine than those receiving supportive care alone. Pain and dyspnea were less severe and cognitive function was better with vinorelbine treatment. Vinorelbine produced some toxicity, but it was not severe. Interestingly, survival was significantly better for patients receiving vinorelbine. Median survival was 21 weeks for patients receiving supportive care and 28 weeks for patients receiving vinorelbine (P = 0.03). Survival at 12 months was 14% on the supportive care arm and 32% on the vinorelbine arm. Using the estimated relative hazard of death analysis, those receiving vinorelbine were 0.65 as likely to die. The response rate to vinorelbine was 20%.
The results of this trial were even better than the ELVIS Group had hoped. They were aiming for an improvement in quality of life, which they obtained, but in addition, they saw significant differences in survival—the median survival improved almost two months and the one-year survival was doubled. The toxicity from vinorelbine was modest. The incidence of grade 3 or 4 leukopenia was only 7% and only three patients stopped treatment as a consequence of constipation.
This was a pretty sick group of patients and they appeared to benefit from the therapy at least as much as younger patients treated with more aggressive and toxic regimens. One implication of this study is that best supportive care may not be a necessary control arm for patients on future trials. Vinorelbine was safe and effective and prolonged survival. It should probably become the standard control arm of any randomized trial that attempts to make further improvements in treatment outcome. Therapeutic nihilism does not seem to be justified when it is clear that both the length and quality of life are prolonged by an intervention. Thus, while the effect of the treatment was modest, it appears that vinorelbine should be the treatment of choice in nonsmall cell lung cancer patients, particularly in those who are over age 70 years. I think we all owe the ELVIS Group a tribute: So ELVIS, thank you....thank you very much.
1. Non-Small-Cell Lung Cancer Collaborative Group. BMJ 1995;311:899-909.
2. Gridelli C, et al. Eur J Cancer 1997;33:392-397.
3. LeChevalier T, et al. J Clin Oncol 1994;12:360-367.