Adjuvant chemotherapy in elderly patients: An analysis of National Cancer Institute of Canada Clinical Trials Group and Intergroup BR.10

Reviewer: Christopher Dolinsky, MD
University of Pennsylvania School of Medicine
Last Modified: June 3, 2006

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Presenter: C. Pepe
Presenter's Affiliation: Princess Margaret Hospital, Toronto, Canada
Type of Session: Scientific

Background

  • There is a high incidence of lung cancer in the elderly.
  • The elderly are under-represented in clinical trials.
  • There is a significant survival benefit with adjuvant chemotherapy after resection of early stage lung cancers which has been demonstrated in a number of recently reported clinical trials.
  • There have not been any previously reported analyses of elderly non small cell lung cancer (NSCLC) patients receiving adjuvant chemotherapy.
  • Platinum based doublet chemotherapy has not been well studied in the elderly.
  • The purpose of this study was to analyze the benefits of adjuvant chemotherapy in young versus elderly patients and compare differences in deliverability, tolerability, and toxicity.

Materials and Methods

  • Stage IB and II completely resected NSCLC patients were randomized to either cisplatin (50mg/m2 D1&8 q4w x 4cycles)/vinorelbine (25mg/m2 weekly x 16w) (n=242) or observation (n=240).
  • For the entire group, the chemotherapy patients had significantly improved overall survival (69% vs 54%, p=0.02).
  • For the purposes of this analysis, elderly patients were defined as older than 65.
  • 327 patients were classified as young, and 155 patients were classified as elderly.
  • Of the elderly patients, 78 patients were observed and 77 received chemotherapy.
  • 157 young patients who received chemotherapy were compared to the 77 elderly patients who received chemotherapy.
  • All baseline characteristics were not significantly different between the young and elderly patients except performance status (PS0 young 53% vs PS0 elderly 41%, p=0.01) and histology (adenocarcinoma 58% young vs adenocarcinoma 43% elderly, p=0.001).

Results

  • The total dose of vinorelbine that could be delivered was significantly lower in the elderly patients (p=.0004).
  • The total dose of cisplatin that could be delivered was significantly lower in the elderly patients (p=0.001).
  • The rates of grade 3 or 4 hematologic toxicity were not statistically different between the elderly and young patients (anemia p=0.47, thrombocytopenia p=0.89, neutropenia p=0.82).
  • The rates of grade 3 or 4 non-hematologic toxicity were not statistically different between the elderly and young patients.
  • No differences were seen in G-CSF use or hospitalization rate between the young and elderly.
  • Despite similar toxicities, elderly patients received significantly less chemotherapy.
  • Fewer elderly patients completed all chemotherapy (40% elderly vs 56% young); and more elderly patients refused treatment (40% elderly vs 23% young).
  • There was no significant difference seen in overall survival when comparing elderly with young patients (56% vs 64%, HR 0.77, p=0.08).
  • There were stark differences noted in overall survival when comparing patients aged <65, 66-70, 71-75, and >75.
  • However, these differences disappeared when disease specific survival was evaluated.
  • Amongst the elderly, patients who received chemotherapy had a significant improvement in overall survival (66% vs 46%, p=0.04).

Author's Conclusions

  • Adjuvant platinum based chemotherapy can be given safely to elderly patients without a significant risk of increased toxicity.
  • Despite receiving less chemotherapy compared to young patients, elderly patients derive a substantial benefit from adjuvant chemotherapy.
  • Chemotherapy in the adjuvant setting should not be withheld on the basis of age alone.
  • Patients aged >75 require further study.

Clinical/Scientific Implications

The authors presented a retrospective analysis of a well designed randomized phase III clinical trial. Considering the dearth of information that clinicians have regarding treatment of the elderly, the authors of this paper should be commended for undertaking this analysis. However, we must remember that retrospective analyses are hypothesis generating, not hypothesis proving. In this analysis, it appears that elderly patients benefit from adjuvant chemotherapy as well as their younger counterparts. The authors state that "despite similar toxicities, elder patients received significantly less chemotherapy";. Another interpretation of this statement would be that BECAUSE of concern of increased toxicity, elderly patients received significantly less chemotherapy. However, regardless of the amount of chemotherapy received, the elderly patients still had a significant survival benefit with adjuvant therapy.