How to Manage Refractory Small-Cell Lung Cancer

In cancer, a response to treatment typically means that the cancer shrinks or disappears. Cancers that don’t respond to treatment are called refractory.

Refractory SCLC isn’t a new or second, unrelated cancer. Refractory SCLC means that treatments didn’t completely work to eliminate the cancer the first time.

Typically, refractory refers to people who don’t respond at all to the initial treatment. Doctors also use it to describe cancer that improves at first but quickly becomes resistant to treatment. If you relapse within the first 3 months after initial chemotherapy, your doctor may refer to it as resistant or chemoresistant cancer.

On the other hand, if you experience a relapse 3 months or more after you start chemotherapy, doctors consider your cancer chemosensitive. If it’s chemosensitive, your doctor may recommend a different treatment regimen than if you were resistant or refractory to the first chemotherapy.

SCLC is typically treated first with chemotherapy. Chemotherapy works by keeping cancer cells from making more cancer cells.

SCLC usually responds to this initial therapy. Between 60% and 70% of people with SCLC will respond to this initial therapy. That means roughly 30% to 40% of people with SCLC have refractory SCLC.

It’s difficult to find precise estimates of recurrence rates for SCLC, but research suggests that most people with SCLC relapse within the first year.

The standard treatment for relapsed or refractory SCLC is topotecan, a chemotherapy drug. Until recently, topotecan was the only drug approved by the Food and Drug Administration (FDA) as second-line treatment for SCLC.

In 2020, the FDA approved lurbinectedin (Zepzelca). The FDA granted Zepzelca accelerated approval based on response rates seen in clinical trials. Full approval will depend on if it can show a clinical benefit in confirmatory trials.

Experts also encourage people with refractory SCLC to enroll in a clinical trial studying a new treatment. Scientists are particularly interested in treatment with immunotherapy drugs known as checkpoint inhibitors. Checkpoint inhibitors work by blocking the proteins that keep your immune system from attacking the cancer cells.

Talk with a doctor if you’d like to explore the benefits and potential risks of participating in a clinical trial for a new therapy for refractory SCLC.

Your outlook depends on the stage of your cancer. Doctors typically split SCLC into two stages.

• Limited stage: Cancer is found only on one side of your chest.
• Extensive stage: Cancer has spread to both sides of your chest or outside your lungs.

Most people with SCLC are already in the extensive stage when they get a diagnosis.

Research suggests that the 5-year survival rate of limited SCLC is less than 15%. The 5-year survival rate for extensive-stage SCLC is less than 2%. This number represents the percentage of people still alive 5 years after a diagnosis.

It’s important to keep in mind that these numbers are calculated based on data from previous years. People diagnosed with lung cancer more recently may have better survival rates than those diagnosed in previous years because cancer treatments continually improve over time.

If chemotherapy fails, your doctor may prescribe another treatment, such as topotecan or lurbinectedin. This is called second-line treatment. In a small percentage of people, refractory SCLC may respond to second-line treatment with topotecan.

In clinical trials of people with relapsed SCLC, topotecan had response rates ranging from 8% to 27% and a median overall survival ranging from 3.7 to 12.5 months.

In a clinical trial of 105 patients, 35% of people with refractory or relapsed SCLC treated with lurbinectedin (Zepzelca) responded to the treatment. In this trial, patients also experienced a median response duration of 5.3 months.

Doctors may also express your outlook in terms of progression-free survival (PFS). PFS is the length of time after treatment before your cancer gets worse.

Research suggests that the median PFS for people with SCLC receiving second-line therapy is roughly 4.6 months. For people with relapsed SCLC receiving third-line chemotherapy, the median PFS is roughly 2 months.

In recent years, clinical trials have studied new treatment options involving immunotherapy. Though more research is needed, these medications show promise in improving the outlook for people with SCLC.

Symptoms of recurrent lung cancer will be the same as the common symptoms of initial lung cancer.

These symptoms may include:

• a persistent or worsening cough
• coughing up blood
• fatigue or weakness
• chest pain
• hoarseness
• shortness of breath
• wheezing
• loss of appetite

However, for many people with SCLC, cancer spreads (metastasizes) to a different body part, such as the brain.

If cancer spreads to your brain during recurrence, symptoms may include:

• headaches
• dizziness
• seizures
• problems with balance
• trouble walking
• slurred speech

Refractory SCLC means that cancer didn’t respond to initial treatment. Though there are other approved treatments you can try, your doctor may also encourage you to join a clinical trial. Talk with a doctor to find out if you’re eligible for any clinical trials in your area. You can also search for clinical trials sponsored by the National Cancer Institute on their website.

If you have refractory SCLC, it’s important to talk with a doctor about your treatment options, including clinical trials. This can include choosing not to have treatment or getting a second opinion. Supportive care, also known as palliative care, is also an option to improve your quality of life.