Excerpts from the Audio Program

Clinical presentation of lung cancer

Lung cancer is often fairly advanced by the time it’s diagnosed. As a result, 90 percent of patients have three or more symptoms at presentation, the most common being cough, hemoptysis, pain and dyspnea. In many cases, these patients were once smokers and their symptoms are caused by chronic obstructive pulmonary disease. Two-thirds of patients with small cell lung cancer and one-third of patients with non-small cell lung cancer have distant disease when diagnosed, so many of them also have symptoms from their metastatic disease, such as bone pain, headache or abdominal pain.

Paul A Bunn Jr, MD

Diagnosing and staging lung cancer

I always explain to patients that cancers are diagnosed by a pathological examination of cells. In lung cancer, these cells are obtained by bronchoscopy, needle biopsy or surgical procedure. We classify lung cancer into four major types — small cell, adenocarcinoma, squamous carcinoma and large cell carcinoma — and because small cell lung cancer has a different behavior and natural history, the other three types are grouped together as non-small cell lung cancer. Once a diagnosis is made, the cancer is then staged using the TNM system. The patient’s prognosis is based on the stage. Staging procedures include CTs, MRIs, PET scans and sometimes mediastinoscopy to biopsy the mediastinal nodes.

Paul A Bunn Jr, MD

Clinical management of patients with Stage I and II NSCLC

Stage I and Stage II represent approximately 25 percent of lung cancer cases. Resection is the standard therapy. Whether patients should receive postoperative chemotherapy is controversial. The majority of patients with Stage I disease treated by surgery alone relapse and die from their lung cancer. In Stage IB, surgery alone cures less than half of the patients. Mounting evidence suggests that adjuvant chemotherapy postoperatively improves survival, but many patients with lung cancer have damage to their heart and lungs caused by smoking. As a result, their tolerance of chemotherapy after a major operation is not very good. Studies show postoperative compliance rates of only 50 to 70 percent with cisplatin-based regimens.

Paul A Bunn Jr, MD

Clinical management of patients with Stage III NSCLC

Surgery alone cures only about 10 percent of patients with Stage III disease. Chemotherapy combined with surgery or radiation has a higher cure rate so a multimodality approach is utilized.

The majority of patients with Stage III lung cancer have N2 disease, indicating mediastinal node involvement. Patients with IIIB disease generally have advanced nodal disease and are treated with chemotherapy and radiation unless they have pleural effusion. In patients with pleural effusion, chemotherapy alone is utilized because we can’t radiate the entire lung. Several randomized trials comparing sequential versus concurrent chemotherapy and radiation have shown that concurrent therapy is better and, although the acute toxicities are worse with concurrent therapy, especially esophagitis and pneumonitis, the late toxicities are about the same. Common side effects of concurrent therapy include fatigue, decreased appetite and difficulty swallowing. These side effects usually peak upon completion of radiation therapy at about seven weeks.

Some physicians administer two cycles of chemotherapy first and then begin chemoradiation; however, we usually start with concurrent therapy. Our patients receive their last two cycles of chemotherapy after chemoradiation, and we find they begin feeling better because the radiation side effects are diminishing, although they still have fatigue. It takes about six weeks for resolution of fatigue, a few months for resolution of hair loss and months to years for resolution of neuropathy.

Paul A Bunn Jr, MD

First-line therapy for elderly patients and patients with comorbidities

I believe elderly patients with a PS2 should be offered either a tolerable two-drug regimen or a single agent. Cisplatin-based, two-drug regimens may not be ideal, but a number of single agents are available including paclitaxel, docetaxel, gemcitabine and vinorelbine. Evidence shows that the combination of paclitaxel and carboplatin might be better than a single agent in elderly patients. The advisability of treating a patient with other illnesses depends on the specific comorbidity. Undoubtedly, some patients who may not have been treated years ago, such as cardiac or pulmonary patients, are being offered gefitinib today. Still, we need to see the data from the current gefitinib randomized trials.

Paul A Bunn Jr, MD

Clinical management of patients with Stage IV NSCLC

Stage IV disease is treated with two-drug chemotherapy and as many as six combinations are considered standard two-drug regimens. Most physicians select a regimen based on experience and convenience. Many patients coming from a distance prefer to be treated every three weeks rather than weekly. We give them the combination of paclitaxel and carboplatin every three weeks and patients tolerate it extremely well. The primary side effects are alopecia, peripheral neuropathy and Grade III-IV neutropenia and thrombocytopenia. Peripheral neuropathy can be dose-limiting because it’s cumulative, so the ASCO guidelines recommend stopping after four cycles unless the patient continues to respond.

Docetaxel is approved for use in the second-line setting for treatment of Stage IV disease. A study presented at ASCO comparing docetaxel with pemetrexed showed they were equally efficacious but pemetrexed was less toxic. Pemetrexed, which is approved for mesothelioma, is a multitarget antifolate that inhibits three enzymes in DNA synthesis.

We participated in a trial of gemcitabine and pemetrexed in the first-line setting and, although the response rate was only 20 percent, the median survival was approximately 13 months. Pemetrexed administered with folate supplementation has a lower rate of myelosuppression than most drugs, it doesn’t cause much alopecia, and it requires only a 10-minute infusion every three weeks.

Gefitinib is approved for use in the third-line setting for advanced lung cancer. However, we know that females, nonsmokers and patients with adenocarcinomas respond better to gefitinib, so if we see a PS2 patient matching these criteria we certainly consider it for second-line therapy.

Paul A Bunn Jr, MD

Administration and side effects of gefitinib

The oral administration of gefitinib is a tremendous advantage for patients who live far from their treatment centers, and I find that every patient prefers oral agents. The primary toxicity site for epidermal growth factor (EGF) inhibitors like gefitinib is the skin, but we don’t know why. Gefitinib causes a rash that clinically looks like acne, but it’s not. There is no infection or inflammatory reaction, so it doesn’t respond to anti-acne approaches. Stopping the drug or lowering the dose is the only way to relieve these symptoms. I have rarely needed to lower the dose for this reason. Some patients who have been on gefitinib for three or four years stop it intermittently and realize an improvement in subtle side effects such as diarrhea and a positive impact on their general well-being. Many of these patients have received chemotherapy in the past and certainly prefer gefitinib.

Paul A Bunn Jr, MD

I have observed a number of good responses to gefitinib. When we participated in the original gefitinib trial, I received phone calls from lung cancer patients all over the United States interested in the drug’s minimal side effects and oral administration. Gefitinib-associated skin rash looks like typical acne and appears mainly on the face, trunk and back. Fifty percent of patients experience it within the first month or two, and 90 percent eventually develop it. It can be pruritic and for some patients it’s a big issue, but it’s certainly preferable to the side effects of chemotherapy. Topical therapies are worth trying but for most patients they aren’t helpful.

Tina Russell, RN, OCN

Rapidity and duration of response with gefitinib

We’ve treated over 150 patients with gefitinib, and approximately six to 10 percent have had objective responses. In some patients the response is dramatic. One patient had received three prior chemotherapy regimens and was nearly dying. We put him on gefitinib and he had a dramatic response that occurred very quickly and has lasted for nearly three years. Another patient was a 42-year-old mother with a pericardial effusion, and she had a partial response to gefitinib that lasted about eight months. A woman in her fifties was treated with gefitinib and was able to go back to school, which was something she always dreamed about doing. She’s been on gefitinib for about two years. Many of these patients report experiencing symptom improvement within two to three days, but in most patients it takes longer.

Karen Kelly, MD

Gefitinib efficacy in specific patient subsets

Gefitinib is a small-molecule receptor tyrosine kinase inhibitor. In the early gefitinib trials, nonsmokers, women and patients with adenocarcinomas and bronchoalveolar carcinomas were more likely to respond. The Southwest Oncology Group (SWOG) conducted a trial of paclitaxel confined to the bronchoalveolar subset, and the response rate and median survival were 14 percent and 12 months, respectively. A SWOG Phase II trial with gefitinib in the same subset had a response rate and median survival of 19 percent and 15 months, respectively.

Similarly, a Phase II trial with erlotinib — another small-molecule receptor tyrosine kinase inhibitor — in patients with bronchoalveolar carcinoma demonstrated a 26 percent response rate. Both gefitinib and erlotinib had a seemingly higher response rate than we see with standard two-drug chemotherapy in bronchoalveolar carcinoma.

Paul A Bunn Jr, MD

Symptom improvement with gefitinib

The median time to symptom benefit from gefitinib is eight days, which I believe is similar to chemotherapy. When chemotherapy works, approximately half the patients have an objective response in the first cycle and 85 percent within the first two cycles, and symptom benefit is usually sooner.

That’s partly because patients with lung cancer generally present with multiple symptoms, so just a 10 percent regression will improve symptoms for most patients. Responses are more dramatic in small cell lung cancer than in non-small cell lung cancer.

Paul A Bunn Jr, MD

We had a patient in his sixties who had received multiple therapies for lung cancer. At one point he was hospitalized and was not expected to live. Fortunately, he survived and when he stabilized he called us to inquire about gefitinib. When he started treatment, he claimed his symptoms improved within six or seven hours of taking the pill.

His quality of life has since improved dramatically, and he was thrilled to experience such impressive results from an oral agent after having tried other treatments that were not nearly as effective. He experienced a rash, but he didn’t mind because his cancer was so much better.

Lyn Magree, BS, CCRP

Nurses’ role in the management of lung cancer

Nurses are an incredibly important part of the team. They have to deal with a plethora of issues — especially in lung cancer patients who tend to be very symptomatic. Nurses counsel patients on managing the symptoms and side effects of therapy. Nurses make certain that a patient’s pain medication is sufficient, that they receive zoledronic acid for bone metastasis or antidepressants for depression. They also teach the patient how to deal with hemoptysis, neuropathy, sleeping problems, nausea, vomiting and constipation from long-acting narcotics. Patients need someone to answer vital questions like: Where should I go if I get sick? Am I going to go to hospice? Where can I get a wig? Can I keep working? That someone is the nurse.

Paul A Bunn Jr, MD

Counseling patients about participation in randomized clinical trials

Sometimes patients are uncomfortable with the concept of randomization in a clinical trial. When we discuss a trial with a patient, we have a consent form. We review why the trial is being conducted, why the patient was chosen for the trial and the number of patients in the trial. Then, we discuss the procedures, risks and benefits. We basically let the patient decide whether they would like to enroll in the trial or receive a standard therapy.

At the University of Colorado, patients often seek to enroll in clinical trials. Sometimes they ask, “What would you tell your parents or grandparents to do?” “What do you think I should do?” We tell them, “You have to make the best decision for yourself. We think you’re a good candidate for this trial. We think it could potentially help you, but it’s your decision.” I have a very positive attitude toward clinical trials because I believe, in addition to receiving a potentially improved treatment, patients also receive a little extra attention.

Susie Lehnerz, BA

Stigma associated with lung cancer

Lung cancer carries a stigma. It seems that the public mentality is that lung cancer patients shouldn’t be treated because they knew the risks of smoking and did it anyway. Many people also believe that we are just wasting time and money treating people who are going to die anyway. For that reason, lung cancer patients are often viewed as second-class cancer patients and don’t get the same support given to other cancer patients.

I believe we should treat all cancer patients the same. It is unfortunate but we have had many young patients who never smoked but were around secondhand smoke, either in their job or in the household, and developed Stage IV lung cancer.

Tina Russell, RN, OCN

Tailoring communications to individual patients

When I meet a patient for the first time, I tell them, “I have information for you. I’d like to share it with you but I need to know that you’re ready to hear it.” I try to establish rapport first, so sometimes that discussion doesn’t occur on the initial visit unless there’s a difficult situation we need to address immediately. Sometimes we don’t appreciate the importance of individualizing communications to patients. We do our best to work with patients so they feel comfortable and are assured they’re receiving quality care, while also trying to be realistic.

Karen Kelly, MD

Applying the biopsychosocial model to patients with lung cancer

The biopsychosocial model is incredibly supportive of the care we want to provide to a patient with lung cancer. In addition to the patient’s physical well-being, their social, psychological and spiritual well-being are tremendously impacted by the diagnosis of lung cancer. If we start with a very specific issue, such as dyspnea, which is common in patients with respiratory tumors, the ability to address that physical issue will have an impact on all the other quality-of-life domains. For example, if my patient’s inability to breathe interfered with his or her social life and ability to take care of children or attend church, and I could help with that issue, I might also be able to have an impact on other quality-of-life domains that are important to the patient.

Karen J Stanley, RN, MSN, AOCN, FAAN

Psychological well-being

A multitude of psychological issues must be addressed for lung cancer patients who are struggling to accept their disease. “I’m going to die. Am I going to die? I thought he said I was going to die. I believe he said it was just a couple of years. I need more than two years.” These patients are struggling with the idea that all of the plans they had made — the story they had written that hasn’t yet been lived — will not be lived. That brings a tremendous amount of anxiety, depression and fear, and this is another piece of this psychosocial realm that oncology nurses need to address. Often the best way to address it is to name it. By naming it, you give the patient permission to talk about it.

Although we would never say, “I know how you feel,” we could say, “I’m concerned about you. You’re looking down these days,” or “I know Dr Smith told you that it looks as though we won’t be able to cure this illness. How are you feeling about that?” In addition to those somewhat existential issues of whether the patient will live or die and how they will manage the time that remains, they deal with depression and its accompanying fears.

The patient’s significant others, family members and friends don’t necessarily want to hear or talk about it. It’s too tough. Practitioners have found that if they give the patient permission to discuss it, the patient’s psychological well-being markedly improves even though the actual physical well-being may not. Certainly, we can do something for the depression, but we can’t fix it until we ask about it.

Patients have identified loss of control as a major issue. As healthcare providers, we have to face the fact that we are not always able to give patients control over their illness. We don’t have control over it, nor do they, so our job as practitioners involved in supportive care is to identify ways patients can have control over other aspects of their lives.

Karen J Stanley, RN, MSN, AOCN, FAAN

Social well-being in the older patient with newly diagnosed lung cancer

Many patients with newly diagnosed lung cancer have advanced disease and might not be well at initial presentation. This is magnified in an elderly population who may have comorbidities and may have already started cutting back on their social life for a number of reasons (e.g., don’t see well, don’t get around as much or have more limited financial resources). We shouldn’t assume that all older people are frail, but they may live a different lifestyle than many of the other patients we treat. When patients with lung cancer have an ill spouse or no spouse and no children in proximity, the problem is significant because the therapies we administer can markedly increase their frailty quotient. Often we’re sending them home to a dangerous, unsupervised situation.

In many older patients, we may have already seen some withdrawal from a typical social life, often because of personal choice. A patient with a significant illness is even less likely to interact with other people because they do not have energy. Additionally, they’re more likely to shun contact with other people if they have lost their hair or look different than before. Problems with body image compound the problem so that isolation or solitude starts to become the norm rather than the exception. When that happens, physical and psychological problems tend to magnify.

Karen J Stanley, RN, MSN, AOCN, FAAN

Spiritual well-being

Patients talk a lot about spiritual well-being, but the healthcare profession has been less inclined to do so. Many healthcare professionals have said, “I wasn’t trained to do this. This is not part of my responsibility. It is the chaplain’s responsibility.” But, as the literature has evolved and our paradigm has shifted, we’re starting to acknowledge that it’s everyone’s responsibility to some degree. The concept of spirituality has been articulated by patients and is of critical importance, but it is an issue that gets shoved aside. We’re now starting to look at it. The Western medical model doesn’t apply very well to some existential issues, and it’s been interesting to see how we’ve used our research process to evaluate how prayer and other beliefs factor into the treatment paradigm.

Spirituality may not be of great importance to every person, but I suspect it’s important to far more people than we know — so we need to ask about it. I have said, “It’s a bit frightening, this place that we’re in. We’ve been told that you don’t have long to live. And I know this has got to be on your mind. Tell me what you’re thinking about it.” Although it might seem as though I were asking about being depressed or anxious, I will gradually get to spiritual issues. For some patients, I might say, “Are you a religious person?” without making the person feel that there’s something wrong with them if they are not.

When we have applied the Western medical model to this issue of transcendence, we’ve discovered that patients who define themselves as having strongly held belief systems do better psychologically during the course of their illnesses. It doesn’t mean they’ll live longer or respond better to chemotherapy, but their emotional state and intellectual outlook will be better. When a person is diagnosed with a life-threatening illness, what was a strong belief system in the past may suddenly become important again. Perhaps they may have strayed away from their faith, but in these circumstances it becomes important again. We need to help make that happen.

Karen J Stanley, RN, MSN, AOCN, FAAN

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