While the elderly make up the largest age-related percentage of people that are diagnosed with cancer, there is an overall paucity of information that compares the effectiveness and tolerability of standard cancer treatments between elderly patients and younger ones. Many people assume that due to their greater age the elderly cannot tolerate the same treatment levels as can younger patients, but there simply isn’t enough statistical information to definitively draw conclusions either way. A few small studies have been done up to now, but the results returned have been generally contradictory, with some showing no difference and others showing the elderly with a worse overall prognosis. In many cases though, the study designs have presented limitations regarding the applicability of the conclusions that can be drawn. And yet, this is a very important question. Toxicity concerns for elderly patients have led some patients to receive an arbitrarily-reduced dosage of a standard therapy, a decision resulting in poorer outcomes for patients who were potentially curable.

In light of these facts, a study was undertaken to examine the overall efficacy and safety of pemetrexed in elderly patients. The researchers conducted a retrospective analysis of the results of three separate Phase III studies involving pemetrexed. Each of the studies had similar treatment plans and dosage requirements, which enabled the aggregation of data that this study relied on. As the majority of people who are diagnosed with mesothelioma are older and may be candidates for Alimta therapy, this present study reveals especially important information for elderly people with pleural mesothelioma or peritoneal mesothelioma.

Overview of the Study

The study aggregated the results of three previous studies involving a randomized use of pemetrexed. The first study was a multicenter, randomized Phase III study involving 456 patients with histologically proven pleural mesothelioma. The sample was randomized so some of the patients received single-agent therapy using cisplatin alone, while the rest received cisplatin + pemetrexed. In the second study, 571 patients with non-small cell lung cancer were randomized to receive either pemetrexed or docetaxel. The third study involved 565 patients with advanced pancreatic cancer. Their treatment plan was randomized to receive gemcitabine alone or gemcitabine + pemetrexed.

When the three studies are aggregated, a total of 764 patients received pemetrexed. Of these patients, 271 (35.4%) were 65 years old or greater and 493 (64.5%) were 64 or under. These two groups were compared in the aggregation study for differences in efficacy, toxicity, survivability and overall response rate.

Patients in the study were mainly Caucasian males, with the elderly group demonstrating an average age of 71 years old and the younger group demonstrating an average age of 55. Most patients between the two groups had Stage IV disease, so outside of their respective ages, the groups were quite similar in overall demographics.

Results

In nearly every comparison between the two groups, response results were the same. To put it a different way, there were not any statistically significant differences between the two groups. 20.9% of the entire population demonstrated some tumor response, but when the data was parsed between the two groups, there was no difference in response, nor in overall survivability between the older group and the younger group. Complete response was achieved in three patients in the elderly cohort and in five for the younger cohort. The elderly group showed a median 4.8 months to progressive disease, while the younger group showed a 4.6 month median figure—a difference, but not a significant one. Overall survival was 8.34 months for both groups. When broken down by tumor type, the authors found no difference in response rate for the mesothelioma and the pancreatic cancer groups between the two cohorts, and while the older group in the NSCLC population demonstrated a lower response rate, it was not a statistically significant rate.

In regards to overall toxicity, a higher percentage of the elderly group (26% vs. 17%) experienced a grade 4 toxicity event, i.e., a life-threatening event requiring significant medical intervention, but this was tempered by four drug-related deaths in the younger group and none in the older cohort. The older group also experienced a higher incidence of myelosupression, which is a condition in which bone marrow activity is reduced, leading to a more limited production of red blood cells, white blood cells and platelets. The most common grade 3 and 4 toxicities experienced in the elderly group included neutropenia, thrombocytopenia, anemia and febrile neutropenia.

Conclusion

The overall results of this study clearly show that the elderly cohort experienced as effective a response to the pemetrexed treatment as did the younger cohort. While they were expected to, and in fact did experience a greater number of high grade toxicity events, if these common events are planned for when treatment begins then there is no reason why the elderly group shouldn’t be given the same treatments as the younger group. There were not any significant differences in survivability, tumor response or induction death rate. For elderly patients, such as those who are most likely to develop pleural mesothelioma or peritoneal mesothelioma, these findings are an important indication that they can respond to the standard mesothelioma treatments as well as younger patients can.

Labels: mesothelioma