Excerpts from the Audio Program

Comparison of small cell and non-small cell lung cancer

The two primary types of lung cancer are small cell and non-small cell. Non-small cell lung cancer represents more than 80 percent of lung cancer. Smoking causes both types of lung cancer, and in small cell lung cancer it’s the cause in virtually 100 percent of patients. In fact, if a patient who’s never been a smoker has a pathologic specimen that has been read as small cell lung cancer, it routinely needs to be questioned. In my 20-year history of seeing only patients with lung cancer, I’ve only seen two patients with small cell lung cancer who were never smokers. It’s very, very rare.

The treatments for both small cell and non-small cell lung cancer are based on stage of disease. Cancers isolated to the lung are treated with surgery. Those in lung and lymph nodes are generally treated with a combination of chemotherapy and radiation therapy, and patients with metastatic disease are managed with chemotherapy.

Most small cell lung cancers have metastasized at the time of diagnosis. Probably less than five percent of patients are ever treated surgically, whereas with non-small cell lung cancer, approximately 15 percent of patients undergo surgery. In general, the rates of response are higher in small cell lung cancer, but stage for stage, longevity is similar to non-small cell lung cancer.

Mark G Kris, MD

Smoking histories in patients with lung cancer

In the United States, approximately seven percent of patients with Stage I lung cancer have never smoked, and 55 percent are former smokers. That means twothirds of patients with early stage lung cancer are “nonsmokers.” Patients who are still smoking are a very difficult group to treat. Many of these patients have been smoking for 50 years and are severely addicted.

The benefits of stopping smoking are tremendous, particularly in small cell lung cancer for which robust data indicate patients who quit live longer. Data also indicate that smoking increases the complication rates at surgery, and many surgeons refuse to operate on patients if they continue to smoke. Many surgeons mandate cotinine testing to confirm patients have quit smoking.

Mark G Kris, MD

Self-blame and isolation associated with lung cancer

Lung cancer patients feel very isolated and guilty. In contrast to patients with other types of cancer, lung cancer patients believe, “I brought it on myself.” They believe society blames them, and they see the extensive support — institutionally, nationally and within families — that other cancer patients receive. Patients actually say, “I wish I had breast cancer,” because they see the network of support available to breast cancer patients at every level, and it’s not available to lung cancer patients.

No core advocacy group of lung cancer survivors exists like with breast, prostate or colorectal cancer. Breast cancer survivors have very effectively lobbied Washington and every year hundreds of millions of dollars are allocated to research funding. Lung cancer patients can’t do that. They’re in a fight for their lives, and they don’t have that “hard core” group of survivors.

Mark G Kris, MD

Patients with advanced disease who cannot tolerate chemotherapy

Approximately 30 percent of patients with lung cancer nationwide are so ill from either comorbid illnesses or the effects of their cancer that they’re not strong enough to receive chemotherapy.

All the data that chemotherapy is beneficial is in patients who are ambulatory. A patient’s level of ambulation makes a big difference. Several years ago we evaluated cisplatin-based chemotherapy, and in patients who were fit enough to work, their chance of responding to therapy was about 50 percent. Patients who had the same extent of disease but, for whatever reason, were not fit enough to work, had a 20 percent chance of responding to chemotherapy. Additionally, patients who are unable to work experience worse side effects than those who work. These data are reproducible, and there’s no data that chemotherapy will improve quality of life in nonambulatory patients.

Informing patients just diagnosed with lung cancer that no active therapy is available is an extraordinarily difficult discussion for everyone, but from a medical standpoint, you’re on very firm ground that chemotherapy will not help these patients. In these situations we catalogue their specific problems and attempt to manage them. For patients who suffer from multiple cancer-related illnesses, we try to palliate as many as possible, and we utilize corticosteroids to a great extent. The constellation of problems in patients with advanced lung cancer are fatigue, pulmonary complaints, shortness of breath, cough, a limitation of activity because of breathing, anorexia and pain. All of those problems can be alleviated by corticosteroids. Sometimes we’re able to get patients well enough so that chemotherapy is an option.

Mark G Kris, MD

Some patients or family members call us out of desperation, telling us their physician told them, “We don’t recommend treatment. We recommend you go home and get your life and paperwork in order and just live out your remaining days.” Sometimes chemotherapy may cause more problems than benefit, and there may be no clinical trials available to them. Those discussions with patients are difficult. Often they don’t understand why you’re denying them treatment for a life-threatening illness. They say, “How can you not treat me? I’m going to die if you don’t treat me.”

We try to establish a balance: we want to help them without hurting them or making them even more miserable. Now, with gefitinib, which is relatively easy to tolerate, we are able to treat some of these patients. It doesn’t always help, but for some of them it may be worth trying. And some patients come in requesting some type of treatment, regardless of whether they are symptomatic or not.

Leslie B Tyson, MS, APN-BC, OCN

Chemotherapy-associated side effects

The chemotherapy for non-small cell lung cancer generally contains either cisplatin or carboplatin as an initial treatment. Side effects include fatigue and, for cisplatin, the potential for nephrotoxicity and hearing loss.

The other class of drugs most commonly utilized is the taxanes: docetaxel and paclitaxel. The side effects include hair loss, neuropathy and the potential for myelosuppression. However, the doses and schedules of the taxanes do not pose as troublesome side effects in small cell lung cancer as in other forms of cancer. Additionally, with weekly schedules of both drugs the myelosuppression occurs much less frequently.

Gemcitabine is the other agent commonly used up front. Gemcitabine frequently causes fatigue, which can be challenging to manage, but it reduces the chance of myelosuppression or nerve damage.

Mark G Kris, MD

Educating patients about adjuvant chemotherapy

At Memorial Sloan-Kettering, Dr Kris is a big proponent of adjuvant chemotherapy. The biggest issue is initiating adjuvant chemotherapy in a reasonable amount of time. Medical oncologists are often the ones who explain the pathology of the tumor and the benefits of adjuvant therapy to patients who are recovering from surgery, and we have seen resistance from patients. Adjuvant chemotherapy should be started within four to six weeks after surgery, but during that period the patient may be fatigued, in pain and constipated, and it’s not the ideal time to talk to them about chemotherapy and its side effects. The numbers don’t always convince patients that adjuvant therapy is something they want to pursue at that particular time.

Surgeons have gotten better at setting up appointments with the medical oncologists before the patients are discharged after their surgery, which has helped us to educate the patient earlier and provide them a window of time to make the decision. We’re using platinum-based regimens for these patients, but as this decade continues, we may have more tolerable agents. Regardless of whether they receive carboplatin or cisplatin, it is going to make them feel worse before they start feeling better.

Ann Culkin, RN, OCN

Educating patients about the side effects associated with a platinum agent

First we discuss nausea, vomiting and loss of appetite that may last a week or longer. We have a protocol, which is an educational piece about hydration; these patients really need to drink adequate fluids the day before, the day of, and two days after they receive a platinum agent. Although anecdotal, the patients who are hydrated seem to do much better. Obviously, drugs like aprepitant (EMEND®), palonosetron (Aloxi®), ondansetron (Zofran®) and dexamethasone enable the patients to do more and feel better.

We’re also concerned about hearing loss and neuropathy. Finally, the patients may just feel poorly. Using a calendar, we explain to them that from this day to, perhaps, this day, they won’t feel like themselves; then, all of a sudden, they’ll start to feel better again. It’s the role of the nurse who administers the chemotherapy to call 24 hours later; then the office practice nurse calls the day after. Patients are constantly in contact with us, and they’re able to articulate how they’re feeling. We can assess, via telephone triage, exactly how they’re feeling and how their hydration is going.

Ann Culkin, RN, OCN

Educating patients with locally advanced disease

Patients with locally advanced disease receive education from both the radiation oncology team and the medical oncology team. At our institution, the visits with the radiation oncologist occur on a different day than the visits with the medical oncologist, so the patients are constantly being assessed. In these patients, we’re most concerned about scheduling and being able to deliver all the radiation and chemotherapy, particularly on the concomitant days. We educate the patients about their chemotherapy and the expected side effects; we also focus on the side effects associated with radiation therapy (e.g., skin changes, esophagitis, fatigue).

Initially, the patient may not necessarily be fatigued from the treatment itself, but from having to be organized and getting to their appointments. We try to explain that they may not be tired from the whole treatment process, but rather from the commute between radiation and chemotherapy and trying to keep their life organized. We also explain that they will need radiation five days a week, Monday through Friday, and chemotherapy once a week. During the first few days of treatment, the patients may be consumed with who will take them to and from therapy.

Ann Culkin, RN, OCN

Radiation pneumonitis

Many patients with locally advanced disease end up with radiation pneumonitis. In the months following the completion of their radiation therapy, we’re still educating those patients about breathing changes and cough, and we’re very in tune to the symptoms of cough and irritation. The typical presentation for radiation pneumonitis is chronic cough that wakes the patient up at night and makes them feel bad. Patients may also experience shortness of breath or breathlessness.

The onset of radiation pneumonitis can occur three to six months, even one year, after the completion of radiation therapy. Although radiation pneumonitis usually goes away, its duration depends on the patient’s response to the treatment interventions (e.g., steroids, cough syrup, cough suppressants). Some patients don’t do well on steroids, especially when they are started on a high dose and tapered quickly. They may need a tapering schedule that lasts as long as two months.

Ann Culkin, RN, OCN

Gefitinib-associated side effects

Gefitinib does not result in any of the common side effects associated with chemotherapy, such as hair loss, neuropathy or myelosuppression. Instead, a rash may develop that appears in the same areas as acne. It is most prominent on the face, head, neck and the anterior and posterior chest. It’s rare to have it on the extremities or the anterior abdominal wall.

The rash is not acne, and treatments such as tretinoin (Retin-A®) are not beneficial. The rash is unusual. The pathophysiology is different and is not very well described. It probably has some modification of the effector cells. Dendritic cells appear in the dermis, and you don’t see the blocked follicles associated with acne. You never see a blackhead.

The rash usually develops after about a week and if you do nothing, two or three weeks later the rash generally gets better, even with continued use of gefitinib. It responds well to both topical and systemic antibiotics, and may be responsive to agents that modulate the immune system, particularly steroids, and often patients are already receiving steroids for other reasons. Immune modulators and creams like pimecrolimus (Elidel®), used for atopic dermatitis, may also provide some benefit.

Diarrhea is usually not a problem at the dose of gefitinib that’s used. We generally tell patients to always carry loperamide (Imodium®) with them and to use it whenever they have a loose bowel movement. It’s seldom a dose-limiting problem.

Mark G Kris, MD

Management of gefitinib-associated rash

In comparison to standard chemotherapy, gefitinib is well-tolerated. The most common side effects are rash and diarrhea. The rash usually develops within the second or third week after beginning treatment, but it can vary. I’ve seen a very delayed onset of rash in some patients. The rash often resolves without intervention (Figure 1.1).

It has been characterized as an acne-like rash, but it truly is not. However, if the rash has pustules, it will respond to minocycline. Hygiene is important, and I counsel these patients as I would a teenager with acne. Sometimes a dose reduction is required if the rash is bothersome, but more often it’s just unsightly and appears mostly on the face and trunk. I provide a lot of support for patients because of the change in their appearance.

Most patients have some type of skin problems, such as increased dryness of the skin, and patients with darker-colored skin may have a darkening on their elbows, finger joints and face. Some patients actually view the rash as a “lucky sign,” because they’ve heard that it might be associated with a better response to treatment. When we first started using gefitinib, patients in the common waiting room would comment, “Oh, you’re so lucky. You’re getting that new drug.”

Leslie B Tyson, MS, APN-BC, OCN

Management of gefitinib-associated diarrhea

The diarrhea associated with gefitinib varies from patient to patient. Many patients are on narcotics, so gefitinib actually helps regulate them. It relieves them of their constipation without having to take laxatives, which is a bonus. For a minority of patients, the diarrhea can be quite bothersome but can usually be controlled with loperamide. Initially, many patients don’t use loperamide correctly.

They should take two pills after the first episode and one pill after each episode until they’re without diarrhea for 12 hours. That’s how we use loperamide, even for patients with three episodes of diarrhea per day. Some patients will have diarrhea every day. I tell them to take two pills upon waking.

Leslie B Tyson, MS, APN-BC, OCN

Patients should pay attention to when the diarrhea starts and to the number of stools. Patients taking narcotics may welcome diarrhea, and they’re happy being told it’s the biggest side effect associated with gefitinib. However, patients with diarrhea may need to go to the emergency room because they become volume-depleted very quickly, and before they know it, they’re hypotensive.

The elderly population, especially, can become volume-depleted rather rapidly. We always have to keep that in mind when 78- to 84-year-old patients begin to take gefitinib. We educate patients about carrying loperamide with them and following the directions on the package — take two tablets with the first loose stool and one tablet with subsequent loose stools. We also ask them to call us if diarrhea occurs, in case we need to stop gefitinib for a few days.

Ann Culkin, RN, OCN

Educating patients with Stage IV disease treated with gefitinib

The first thing these patients receive is written material in the form of a fact card, because they don’t always remember what they are told in the office or exam room. At Memorial Sloan-Kettering, we write our own fact cards, which are reviewed, edited and approved by a committee of PhD nurse educators and the chiefs of service. The fact cards contain the drug’s name, phonetic pronunciation and early and late side effects. Symptom management and the reasons to call the doctor would also be on the card that the patients take home.

Patients are provided with written information about the management of skin changes and diarrhea. We always ask patients to call us if they develop diarrhea and need to take loperamide, so that we can keep track of them and know whether we need to stop gefitinib for a few days to let them recover. Since gefitinib improves symptoms in a matter of days, once patients start feeling better, we don’t hear from them as often. The nurse who has educated them must diligently keep track of these patients to find out how they’re doing.

Ann Culkin, RN, OCN

Counseling patients about the potential benefits of gefitinib

Docetaxel, which was FDA-approved for second-line therapy in the randomized trials, resulted in tumor regression in seven percent of patients and provided a modicum of symptom relief to patients. The data from the clinical trials of gefitinib suggest that major regressions occur in approximately 11 percent of patients, and the rate of symptom improvement is about 39 percent (Figure 1.2).

A potential explanation for symptom improvement in the absence of clinical response may be the definition of response, which is a 50 percent reduction in tumor volume. A patient with a 49 percent tumor regression would be classified as a nonresponder. Clearly, patients will improve symptomatically if their tumor shrinks by 49 percent. For example, a small shrinkage of a tumor may relieve a breathing obstruction or relieve pain from a nerve compression.

Mark G Kris, MD

Therapy with an oral agent makes a tremendous difference because the patient can be in control by self-administering the pill. For some reason, Americans have the idea that a pill can fix anything and that a pill is better. In trying to explain chemotherapy and the infusion into the vein, it’s often misunderstood and patients are afraid of it, because chemotherapy is called “the poison.” The first question patients ask is, “Why can’t I have the pill?” Of course, everybody would like to take a pill to cure their cancer.

Ann Culkin, RN, OCN

Rapidity of symptom improvement with gefitinib

If we’re affecting the growth of cancer by turning off one of the molecular switches, the effects of the cancer reverse dramatically. That’s exactly what happens with gefitinib in lung cancer. Patients who are symptomatic and realize a benefit from gefitinib experience that benefit within days. In clinical trials, one-half of patients who realized a benefit experienced it within two weeks, and virtually every patient had it by four weeks. That’s very different from traditional chemotherapy, with which it takes longer for patients to respond.

With this disease, a patient knows long before the doctor does an imaging study that the drug is helping. It’s also reassuring to me because it makes me think that our hypothesis that we are turning off a switch is indeed what’s happening.

Patients who were oxygen-dependent or wheelchair-dependent because of breathing difficulties will tell you that by the next morning they didn’t have the need for oxygen, and two or three days later they were walking across the room. It’s wonderful for the patient and the healthcare professionals to see that kind of benefit. What makes it even more astounding is that these benefits happen after other options have been exhausted. Most patients who have received gefitinib have had surgery, radiation and multiple rounds of chemotherapy and still had progressive cancer.

For patients who have no options left, getting out of the wheelchair is really amazing. For patients who are most vulnerable to side effects, who have had multiple prior therapies, receiving a tablet that doesn’t have the usual chemotherapy-related side effects is a welcome change.

Mark G Kris, MD

The symptom relief associated with gefitinib usually includes an improvement in the patient’s cough. If the patient has a cough — particularly a patient with bronchoalveolar carcinoma (BAC) who has a chronic wet cough, it seems to dissipate. In patients with BAC, not only does their cough go away, but they also feel better. I’ve had hospice patients who have taken gefitinib and actually improved remarkably over a matter of days, mostly related to cough.

When we were first using gefitinib as a single agent, it was an amazing thing. I would say to Dr Kris, “You’re not going to believe it; their cough is gone.” The reduction in cough usually occurs between three and five days of therapy. We often see a reduction in their pain and shortness of breath. Patients will want to know when they will have their next CAT scan or X-ray, but we always say to them, “You will know first, and we will know second, if this drug is working for you.”

Ann Culkin, RN, OCN

Duration of benefit with gefitinib

One of my first patients to receive benefit from gefitinib started the drug five years ago, and she continues to realize benefits. She had advanced disease and had received four prior lines of chemotherapy, and her cancer was growing with each progressive scan.

In most patients the responses have not lasted that long. One year seems to be a fairly common duration for patients who have had benefit. When gefitinib stops working, it’s a different pattern than with chemotherapy. For the average patient on gefitinib, if you compare any scan two or three months before they’ve had a response, you don’t detect a radiographic progression. However, if you go back two scans, comparing it to a scan done six months before, you can detect it. But if you did that with the sixmonth and the nine-month scan, you still would not be able to detect it.

Mark G Kris, MD

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