Gemcitabine Plus Vinorelbine Offers Better Survival Than Vinorelbine Alone in Elderly NSCLC Patients

NAPLES, Italy—In elderly non-small-cell lung cancer (NSCLC) patients, gemcitabine (Gemzar) combined with vinorelbine (Navelbine) was associated with significantly better survival in comparison to treatment with vinorelbine alone, Giuseppe Frasci, MD, reported at the 36th ASCO Annual Meeting.

“Increasing interest in the treatment of elderly NSCLC cancer patients is mainly due to the demographic changes that are taking place in Western countries,” said Dr. Frasci, Division of Medical Oncology A, National Tumor Institute, Naples, Italy. For lung cancer, more than 50% of cases occur in people over age 60 and 30% in people over 70.

This population is characterized by several features that must be considered when selecting a chemotherapy regimen, Dr. Frasci said. These include physiologic changes in the functions of the main organs and a higher prevalence of concomitant disease that may impair the tolerability of the disease or of treatment.

Dr. Frasci reported that this Southern Italy Cooperative Oncology Group (SICOG) phase III trial was conducted to compare survival and quality of life with the gemcitabine plus vinorelbine regimen (GV) vs that of vinorelbine (V) alone.

In this study, NSCLC patients with stage IIIB or IV disease, between 71 and 85 years of age with an ECOG performance status of 2 or below, were randomized to receive either gemcitabine 1,200 mg/m² plus vinorelbine 30 mg/m² on days 1 and 8, every 3 weeks or vinorelbine 30 mg/m² on days 1 and 8, every 3 weeks.

Survival was the main end point, Dr. Frasci said. “We expected to prolong the median survival time by 50%.”

He said that the researchers did not exclude patients with CNS involvement provided that they were asymptomatic. The number and weight of comorbidities was assessed using the Charlson probability scale.

The total sample size planned was 120 patients per arm, with an interim analysis after half of the patients had been enrolled. Early termination of the study was planned if the experimental regimen showed better survival at a P level of less than .01.

When at least 12 weeks had elapsed from the accrual of the last patient, survival data of the first 120 eligible patients (V = 60, GV = 60) were analyzed.

The median survival in the whole population was 24 weeks, 25 weeks in stage IIIB disease, and 21 in stage IV disease.

Median survival was 29 weeks in the combination arm, compared with 18 weeks in the control arm.

There was also a significant difference in time to symptom deterioration, 21 weeks for GV vs 13 weeks for V alone, and there were no major differences in toxicity between the groups.

The response rate to the GV regimen was 22%, and for the V regimen, it was 15%.

Quality of life differed between the groups. “We had 62% of patients with the score improved or stable in the combination arm, as compared to 40% improved or stable in the standard treatment arm,” Dr. Frasci said.

Among the nonhematologic toxicities, vomiting, fatigue, constipation, and loss of appetite were the most frequent causes of patient complaints, and they are occurred in almost half of the patients, Dr. Frasci said.

“The number and weight of concomitant diseases, together with the performance status, have a major role in impairing the tolerance of the treatment,” Dr. Frasci said. “A more accurate selection of patients, and a personalized drug dosing could be advisable in future trials.”

As planned, the study was closed early, “since the null hypothesis can be rejected at the P = .01 significance level,” Dr. Frasci said. The gemcitabine/vinorelbine combination regimen is now considered the SICOG reference first-line treatment for elderly NSCLC patients.