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Treatment of Locally-Advanced NSCLC in the Elderly: As Individualized as Medicine Gets
Dr Sanborn

“Locally-advanced NSCLC” is a term generally applied to lung cancers with tumors that have either grown into major structures (such as vertebrae or spine bones, the central airways, or involve the main blood vessels supplying the lung or central chest) or those cancers that have spread to lymph nodes in the central chest (the mediastinum). In the case of many of these cancers, removing them with surgery is not possible, but treatment with the combination of chemotherapy and radiation given at the same time may be used with the goal of curing the cancer.

While administering chemotherapy and radiation at the same time (termed “concurrent therapy”) is more effective at killing cancer cells than when the treatments are given separately, this approach also causes increased side effects for the patient. Side effects may include nausea, vomiting, neutropenia (decreased levels of white blood cells which can lead to increased risk of infection) with or without infections, anemia, fatigue, and pain with swallowing (from radiation “sunburn” to the esophagus). In order for a patient to tolerate this rather stout combination, they need to be fairly healthy and active, and to have a strong physical reserve (measured with a term “performance status”).

Most studies of the combination of chemotherapy and radiation, although not excluding older patients, have enrolled younger patients. Typically, the average age of patients enrolled on trials like these is 64 or 65. This allows for decent conclusions to be drawn for patients of this age group and younger, but how do these studies apply to the elderly; patients 75, 80, older?

Data regarding elderly cancer patients is sadly lacking throughout all cancer fields, and data regarding patients over the age of 80 especially is virtually absent. This is due to a variety of reasons, including an increase in other medical problems (such as heart disease, complications from diabetes, or a history of other cancers) as people age that may make them not candidates for trial participation, concerns on the part of the patient or the doctor that a clinical study may cause too much toxicity, or even hesitancies of family or caregivers regarding clinical trial participation.

Despite the lack of elderly patients enrolled in clinical studies, as previous posts have pointed out, cancer is being diagnosed more and more frequently in elderly patients. Doctors are left with minimal data to refer to in deciding what the best treatment approach may be.

In general, the greatest predictor of tolerance of therapy regardless of age is performance status. Those patients who are able to be up and active and moving around through more than half of their day have a much better chance of tolerating chemotherapy and radiation. Those patients who are unable to be active that much of the day have a much higher chance of severe side effects, including life-threatening toxicities.

When I meet with an elderly patient to discuss treatment options for locally-advanced NSCLC (and in my book this means a person who is at least 75), we carefully review all medical conditions as well as kidney and liver function. Performance status is critical, and I usually have a patient describe for me exactly what their typical day’s activities are like.

For those patients who have a good performance status and who are otherwise fairly healthy, I generally recommend the combination of cisplatin and etoposide with radiation. This combination so far has the best reported survival outcomes in phase III trials (median survival of 24 months in the Hoosier Oncology Group study and 35 months in the Southwest Oncology Group study). Although it has never been compared in a head-to-head trial with weekly carboplatin and paclitaxel (a very popular regimen because of fewer side effects), the median survival of 12-14 months that has been fairly consistently shown with this regimen (including in the phase III study by the CALGB) has left me and many other oncologists less than impressed with it if a person is able to tolerate cisplatin and etoposide.

I generally take the approach that if the combination is going to be given with the attempt to cure, the regimen with the best outcome should be used. That being said, there are definitely times when I recommend the weekly chemotherapy in elderly patients (or in patients of any age). If kidney function is borderline, cisplatin can have an increased risk of irreversible kidney damage. If a patient has a preexisting neuropathy (nerve damage) from another medical condition, cisplatin may make this worse and can significantly damage the long term quality of life.

There are also elderly patients even with a good performance status who are “frail”. An 83 year-old patient who is active throughout their day may need less of an insult from treatment to significantly decrease their independence and functionality. This aspect of the decision-making process is very difficult to measure on paper or in a trial; it is the “individualized medicine” aspect that must occur when the doctor, patient, and ideally other family or caregivers are sitting together in the exam room.

I have definitely treated patients in their 80s with cisplatin and etoposide with radiation and they have tolerated the treatment fine. I have other patients in the same age group who have received carboplatin and paclitaxel with radiation. There are others for whom the combination with any chemotherapy would be harmful, and in those situations we have given radiation alone, palliative therapy instead of curative therapy, or no therapy at all.

My follow up of elderly patients undergoing chemotherapy with radiation involves frequent clinic visits and lab testing and ongoing assessment of tolerance and performance status. Sometimes treatment plans need to be changed in the middle of the treatment process if side effects are becoming too great. This may include holding doses of chemotherapy, switching chemotherapy types, or discontinuing chemotherapy or radiation entirely depending upon the situation.

Part of the decision-making process lies with the oncologist, who must judge the risk and benefit ratio to see how it would apply to the older patient they are treating. A major part of the decision lies with the patient, who also must decide how aggressive they want to be in terms of the risks of side effects versus quality of life. Each decision must factor in the unique aspects of the individual patient.

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