Walter Sall, MD
Abramson Cancer Center of the University of Pennsylvania
Ultima Vez Modificado: 14 de noviembre del 2003
Presenter: Chandra Belani, MD
Affiliation: University of Pittsburgh
Lung cancer continues to be the leading cause of cancer death in the United States, with approximately 80% of cases being NSCLC. The overall survival and median survival time in patients with metastatic disease remains dismal. There have been advances in the treatment of both curative cases and metastatic disease in recent years. These advances consist mainly of combination chemotherapy regimens using platinum containing compounds. In definitive cases, the use of combination chemotherapy either sequentially or concurrently with radiation therapy has resulted in increased survival.
Elderly patients (> 70 years old) make up 35-40% of newly diagnosed cases of NSCLC. They are, however, underrepresented in many of the clinical trials that have proven the effect of combination chemotherapy. Therefore, there is uncertainty as to whether or not elderly patients can tolerate this aggressive therapy and whether it is beneficial in elderly patients. To help answer this question, a subset analysis of a previously published randomized study (Belani, JCO, 2003) was presented.
In this study, three different schedules of combination carboplatin and paclitaxel were examined. Arm 1 was carboplatin AUC=6 every 4 weeks with paclitaxel 100 mg/m2 in three out of four weeks. Arm 2 consisted of carboplatin AUC=2 with paclitaxel 100 mg/m2, both given in three out of four weeks. Arm 3 was carboplatin AUC=2 with paclitaxel 150 mg/m2 both given in six out of eight weeks. All patients completed 16 weeks of therapy. The overall response rate was 32%, 24%, and 18% for arms 1,2 and 3, respectively. Time to progression was 30 wks, 21 wks, and 27 wks in arms 1,2 and 3, respectively. Median survival time was 49 wks, 31 wks, and 40 wks in arms 1, 2, and 3, respectively. The conclusion from the study was that arm 1, with carboplatin AUC=6 every 4 weeks and paclitaxel 100 mg/m2 given 3 out of 4 weeks was most efficacious (though from data presented, many of the endpoints were not statistically significant). In this arm, the incidence of febrile neutropenia was 2%, with other toxicities similar to the other arms.
Out of the 403 patients enrolled into this trial, 28% were > 70 years old. In these elderly patients, median survival time, overall one and two year survivals, and time to progression were very similar to the group as a whole. This was especially the case in the most efficacious arm, arm 1. Though there was some variability (likely due to smaller numbers) in the other arms, these same trends continued. Elderly patients had a higher incidence of neutropenia (14% vs 5% in arm 1), though, again, the incidence of clinically significant febrile neutropenia was very small.
The conclusion of the presenter was that elderly, good performance status patients should receive optimal regimens of chemotherapy. It was also stressed that there is a need for elderly specific trials comparing single agents to combination chemotherapy to ensure that the same trends are noted. There is also a need for a comprehensive review of the pharmacokinetics and toxicities in the elderly. Based on this report, as well as other reports that analyze elderly patients, these conclusions hold true. These elderly patients, as all patients, should be monitored carefully, as the aggressiveness of the treatment regimen increases. This is especially true in poor performance status patients. Specifically designed trials for the elderly are needed to make full conclusions as this study was not designed to look at differences in the elderly population. With the baby boomer population increasing in age, physicians will be further compelled to make chemotherapy treatment decisions in the elderly and further information on this topic is needed.
Aug 10, 2011 - Despite more toxic effects, doublet chemotherapy with carboplatin and weekly paclitaxel is associated with significantly higher survival benefits than monotheraphy with either vinorelbine or gemcitabine in elderly patients with advanced non-small-cell lung cancer, according to a study published online Aug. 9 in The Lancet.