Phase II clinical trial
The recent study was a phase II clinical trial meant to find out how effective Zelboraf was in treating patients with metastatic melanoma, and how it affected overall survival.
For this study, researchers enrolled 132 patients with stage IV metastatic melanoma, all who carried the BRAF V600 genetic mutation. All patients had been treated previously for the disease and were given same dose of vemurafenib twice a day. Patients who experienced unacceptable side effects or a worsening in their disease were allowed to stop treatment.
The patients underwent tumor imaging — either magnetic resonance imaging (MRI) or computed tomography (CT) — at the beginning of the study and every six weeks after. Researchers used these scans to assess any changes in tumor size and response to the treatment. The data was then analyzed to determine the proportion of patients who responded to treatment.
Study participants were followed up for an average of 12.9 months. The researchers found that:
• More than half or 53 percent of patients showed some reduction in the size of their tumor.
• Among those that responded to the treatment, eight patients achieved a complete response (6 percent of total study group), and 62 patients achieved a partial response (47 percent).
• Among those that responded, 23 (33 percent of responders) maintained that response at the study’s end.
• Median overall survival was 15.9 months; 62 patients (47 percent) were still alive at the study’s end.
• The overall survival rate 77 percent at six months, 58 percent at 12 months and 43 percent at 18 months.
While phase I trials are done to test the safety of a drug, phase II trials are designed to find out how effective the new drug is in highly controlled settings. Phase II trials are also used as a confirmatory step before a drug can be given to wider research populations.
But these trials don’t involve a control group of patients, so they can’t compare how effective a new drug is against current treatment. Such control-group comparisons are usually performed in phase III trials.
More effective than chemotherapy
Such a phase III study, in fact, was started, with some study patients randomly selected to receive vemurafenib or standard therapy. But, according to the NHS, the trial was stopped before it was completed when an interim analysis showed that vemurafenib significantly improved patients’ progression-free survival and six-month survival, compared with standard care. At this point, for ethical reasons, all participants were given the new drug.
This phase III trial, which was done on 675 patients with previously untreated, inoperable late-stage metastatic melanoma with the BRAF mutation, showed that advanced melanoma patients treated with Zelboraf in a clinical trial were 63 percent less likely to die than patients given chemotherapy.
After an average of three months of treatment, patients receiving Zelboraf had a 63 percent reduced risk of death compared to patients given the chemotherapy drug dacarbazine.
The findings were presented during the meeting of the American Society of Clinical Oncology, were reported in June 2011.
The trial results were “better than we expected,” said Dr. Paul Chapman of Memorial Sloan-Kettering Cancer Center in New York and the study’s lead investigator. The testing plan was changed after it became clear that patients were faring better on the targeted drug, Dr. Chapman said.
Last August, Roche said that Zelboraf would cost just over US$56,000 for a six-month course of treatment in the U.S. It has yet to announce a price in Europe.
But while Zelboraf, one of a new generation of cancer drugs targeted at patients with a specific genetic make-up, offers hope — it isn’t a cure since the cancer eventually becomes resistant to the drug, both the NHS and Dr. Kate Law, director of clinical and population research at Cancer Research UK, point out.
“We’re getting somewhere with these targeted drugs but we have a whole raft of research still to do to address the issue of resistance,” she told the BBC.
Side effects from Zelboraf include: back pain, constipation, cough, diarrhea, dizziness, dry skin, extreme photosensitivity, hair loss, headache, joint or muscle pain, loss of appetite, nausea, rash, secondary growths, taste changes, thickening of the skin, tiredness, vomiting and weakness.
Patients are advised to see the doctor immediately if they experience any of these severe sign of allergic side effects—which are severe:
• Severe allergic reactions—rash, hives, itching, difficulty breathing or swallowing, tightness in the chest or throat, swelling of the mouth, face, lips, or tongue, unusual hoarseness
• Burning, numbness, or tingling
• Eye pain, swelling, or redness
• Fast or irregular heartbeat
• Mouth sores or blisters
• Red, swollen, blistered, or peeling skin
• Severe or persistent dizziness
• Swelling of the hands, feet, or ankles
• Symptoms of liver problems—dark urine, pale stools, yellowing of the eyes or skin, unusual tiredness, nausea, or vomiting, persistent loss of appetite, severe stomach pain
• Tingling, pain, redness, or swelling of the palms and soles
• Vision changes –blurred vision, sensitivity to light
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