Navelbine, also known as vinorelbine, is a plant-based chemotherapy drug that is currently being tested in clinical trials as a viable treatment for pleural mesothelioma. While navelbine has been found to not be as effective as pemetrexed-cisplatin treatment combinations in treating patients with no previous chemotherapy, it’s predominantly being investigated as a potential second- or third-line or palliative treatment option.
What is Navelbine?
Mesothelioma is a rare and aggressive form of cancer that manifests in the mesothelium lining of the chest, abdomen and heart. A combination of surgery, radiation therapy, and chemotherapy is commonly used to treat mesothelioma. However, some widely spread and unresectable cases (those that cannot be removed through surgery) heavily rely on the outcomes of chemotherapy. Currently, the only Food and Drug Administration (FDA) approved chemotherapy drugs for the treatment of mesothelioma are pemetrexed (Alimta) and cisplatin. Commonly used together, this drug combination has a modest impact on survival. For this reason, new drugs like Navelbine are always being studied in the hopes of finding better treatment options for patients diagnosed with mesothelioma.
Did You Know? Navelbine, also known as vinorelbine, is a vinca alkaloid chemotherapy drug derived from the periwinkle plant that was approved by the FDA for the treatment of non-small cell lung cancer in 1994. Vinca, or plant alkaloids are semi-synthetic, meaning they are partially chemical and partially plant. Over the past few decades, navelbine has been studied as a viable chemotherapy drug for the treatment of pleural (chest) mesothelioma.
Studies have shown that navelbine is not as effective in increasing survival rates and life expectancy in comparison to pemetrexed-cisplatin treatments. However, navelbine is being actively studied as a potential second-line treatment, a line of treatment following a patient’s first round of therapy, as a means of relieving pain and improving quality of life without shrinking tumor mass (also known as palliative treatment), and as a maintenance treatment to extend patients remission.
How is Navelbine Administered?
Navelbine can be administered in two different ways, either orally or intravenously. The benefits and effects of both treatment methods, along with dosing variations, are currently being studied in clinical trials.
If administered through an intravenous (IV) drip, patients are generally given navelbine in several cycles, each around half an hour long. Results have been most favorable when treatments are given weekly, in dosages between 20 mg and 30 mg. If administered orally, doses of 20, 30 and 80 mg exist, depending on doctor recommendations based on patient characteristics and intended outcomes. Variations in both treatment cycles have been recorded, depending on if navelbine is being prescribed for first-line, second-line, palliative, or maintenance treatments.
Administering navelbine in its capsule form may be beneficial as treatment can be given out of the comfort of patients homes. As mentioned above, more severe side effects are observed when the drug is taken orally, and patients need to be careful the capsules are not damaged in any way as punctures can cause mouth sores and localized pain.
Chemotherapy drugs are to treat various forms of cancer due to their ability to interfere with cell growth—either through initiating cell death or causing problems in cell-cycle regulation. Healthy cells duplicate their DNA and then divide into new cells, but after around 50 divisions, healthy cells are programmed to die (apoptosis). Programmed apoptosis helps to prevent abnormalities and ensures genetically mutated cells are removed from the body.
When healthy cells become cancerous, the reason they are so dangerous is due to their loss of this suicidal programming, and they replicate and spread at increased rates. Chemotherapy drugs chosen to treat mesothelioma are able to kill cancerous cells in tumors or small lumps found in the mesothelial lining of the chest, abdomen and heart.
Navelbine is classified as an antineoplastic agent. This means that it is able to bind to microtubules proteins in cells. Microtubules are seen in the last stages of cellular division as they help cells split their DNA between two new cells. When navelbine binds to these microtubules, mesothelioma cells are unable to divide which leads to their self-destruction.
Mesothelioma Research Update
A current clinical trial suggests that in order for navelbine to have an effect in treating mesothelioma, a gene called BRCA1 is needed in order to induce cell death. This gene has been shown to be absent in 38% of mesothelioma case. This study is aiming to establish whether patients treated with navelbine live longer and whether patients should be tested for BRCA1 gene before being administered navelbine.
Navelbine Drug Combinations
Mesothelioma cells are often resistant to cytotoxic treatment, which involves killing cancerous and sometimes healthy tissue. This resistance may be due to cells intrinsic apoptosis resistance. For this reason, doctors generally combine chemotherapy drugs that work to kill cancer cells through different mechanisms. Studies have also shown that chemotherapy treatments with single agents achieve low response rates in mesothelioma patients, generally around 20%.
Navelbine has been administered on its own as well as in combination with other drugs through various clinical trials treating pleural mesothelioma. In patients who did not receive any previous chemotherapy treatments, combinations of navelbine and cisplatin (an FDA approved chemotherapy drug for mesothelioma) have been used, along with navelbine and oxaliplatin—a drug commonly used to treat renal and colon cancer.
As another form of first-line treatment, navelbine has been administered as part of a triplet regiment in combination with cisplatin and gemcitabine (commonly used to treat pancreatic and ovarian cancer). When navelbine is used as a first-line treatment, either on its own or in combination, significant toxicities were reported with minimal responses observed. For this reason, navelbine is now being investigated as a second-line and palliative treatment method in combination with gemcitabine.
Navelbine is currently approved by the FDA to treat non-small cell lung cancer. However, clinical trials have been ongoing for years to test its ability to treat mesothelioma—pleural mesothelioma in particular. Clinical trials are used to assess whether a drug is safe and effective in treating a disease, with various phases numbered from 1 to 4. Each phase of a clinical trial increases in treatment group size and monitors the side effects and treatment results experienced by each patient. The FDA requires the drugs to pass through each phase before being administered to the general public.
Mesothelioma Research Update: Numerous clinical trials are currently taking place to test the efficiency of navelbine in treating patients as a first-line, second-line and palliative treatment. A phase 2 clinical trial that is studying the effectiveness of navelbine (vinorelbine) as a single-agent first-line treatment is showing a partial response rate of 24%, a stable disease rate of 55% with 21% of patients experiencing disease progression during treatment.
Another clinical trial is comparing the effectiveness of navelbine in patients with non-small cell and mesothelioma—this trial is currently in phase 1. Clinical trials are also testing navelbine in its ability to treat mesothelioma recurrence as a second-line treatment, these trials include a phase 2 study comparing anetumab ravtansine and navelbine as single agents and another phase 2 trial studying orally invested navelbine as a single agent.
Navelbine is also being compared against gemcitabine and antibody immunotherapy as a third-line treatment method for patients with advanced pleural mesothelioma in a phase 3 trial.
Lastly, as mentioned above, navelbine has shown promise as a viable treatment for palliative care to improve patients quality of life who are unable to tolerate other treatments. There is currently a phase 2 clinical trial being conducted to compare the palliative therapy effects of mitomycin, vinblastine, and cisplatin versus navelbine alone. If a patient is interested in participating in a clinical trial they should touch base with their doctor to understand the possible benefits and risks.
Navelbine Side Effects
The side effects of navelbine are comparable to other chemotherapy drugs that are unable to distinguish between cancerous cells and healthy cells. This being said, navelbine destroys healthy cells throughout the body, which brings varying degrees of negative side effects.
Navelbine can be administered through an intravenous (IV) drip or pill, with side effects generally being more severe when the drug is taken orally. Common side effects include low red and white blood cell counts, anemia, nausea, vomiting, constipation, muscle weakness, fatigue, alopecia and mouth sores (when taken orally). Rare side effects can also be observed, which include numbness or tingling in limbs, hemorrhaging, pain around the injection site, blood in urine, abdominal pain, blood pressure fluctuations, and diarrhea.
Doctors will monitor patients blood tests for fluctuations in blood cell counts along with kidney and liver functions to ensure minimal harm. With decreases in blood cells, white blood cells in particular, a patient’s immune system can be compromised which can list to a higher risk of infection. All side effects should be communicated to a patient’s doctor with treatment stopping if extreme or severe effects are experienced.
For more information on participating in clinical trials for Navelbine, contact our Patient Advocates today.