The study, conducted by scientists from Dana-Farber Cancer Institute and the Eastern Co-operative Oncology Group, and funded by the National Cancer Institute (NCI), was presented at the recent annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago. Earlier results of the trial were made public by the NCI in December 2013 because of the strong positive findings.
Most Common Cancer in Men
According to the Centers for Disease Control and Prevention (CDC), prostate cancer is the most common cancer among men in the U.S. It is also one of the leading causes of cancer death among men of all races and Hispanic-origin populations. In 2010, 196,038 men in the U.S. were diagnosed with prostate cancer and 28,560 men in the U.S. died from prostate cancer.
The current treatment for men who are newly diagnosed with prostate cancer that has spread widely, and whose cancer depends on male hormones to grow, is hormone-blocking medications — androgen deprivation therapy (ADT). Most tumors eventually outgrow their need for hormones and the cancer progresses, and only then do these patients begin chemotherapy.
Delaying Development of Resistance
Principal investigator Christopher J. Sweeney, MBBS, of Dana-Farber’s Lank Center for Genitourinary Oncology, said in a press statement, “This is the first study to identify a strategy that prolongs survival in newly diagnosed, metastatic prostate cancer.”
Sweeney set out to show that immediately hitting the cancer with chemotherapy, in addition to hormone treatment, would impair the tumor cells’ ability to repair damage, delaying the development of resistance.
The study included 790 men who were newly diagnosed with metastatic disease. They were randomized to receive ADT alone or ADT with docetaxel (brand name Taxotere) over 18 weeks. In the ADT-only group, 124 patients were given docetaxel when their cancer worsened. In the ADT-plus-docetaxel group, 45 patients whose disease progressed received additional docetaxel.
Emphasizing that the benefit is substantial, Sweeney said the strategy warrants this being a new standard treatment for men who have high-extent disease (whose cancer has spread to major organs and/or the bones),and are fit for chemotherapy.
Ashutosh K. Tewari, M.D., chairman, Milton and Carroll Petrie Department of Urology, Icahn School of Medicine at Mount Sinai in New York told Healthline, "The early results from this NIH funded study provide strong evidence to support the utilization of docetaxel along with ADT in high volume metastatic prostate cancer patients. High volume metastatic prostate cancer is defined as cancers that have infiltrated other organs like the lung or liver, or those that have multiple bone lesions. Long-term follow-up will help underlining its utility in low-volume metastatic prostate cancer patients."
Bruce E. Johnson, M.D., Dana-Farber’s chief clinical research officer, said in the press statement, “The prolongation in survival seen in the prostate cancer patients participating in Dr. Sweeney’s study is very impressive, dramatically longer than the typical 2- to 6-month prolongation typically observed in successful studies of other metastatic adult solid tumors.”
Patients Survived More Than a Year
At a median follow-up of 29 months, 136 patients in the ADT-only group had died versus 101 in the group that received both drugs. This translated into a median overall survival of 57.6 months for men who received early chemotherapy, compared with 44 months in the group given ADT as the only initial treatment.
In the 520 patients who had high-extent disease, treatment with ADT plus docetaxel had a median overall survival of 49.2 months versus 32.2 in the ADT-only group — a difference of 17 months.
Most of the striking survival benefit with early use of docetaxel was found in men with a high burden of metastatic disease, said the researchers.
The most serious side effects were neutropenic fever and neuropathy; one patient died as a result of treatment.
Docetaxel Also Delayed Disease Progression
The addition of docetaxel lengthened survival and also delayed disease progression, as measured by an increase in prostate-specific antigen (PSA), the appearance of new metastases, or worsening symptoms. The men receiving docetaxel had an average of 32.7 months before the cancer progressed, as determined by worsening scan results or symptoms, compared with 19.8 months for hormone therapy alone.
According to Sweeney, early chemotherapy increases the chances that certain patients with metastatic prostate cancer have a longer time without symptoms from cancer, and also live longer. He went on to say that more time is needed to assess the benefit of the drug combination in the men with lesser burdens of disease, as their median survival has not yet been reached.