Three-Week Chemotherapy Dosing Reconfirmed as First-Line Treatment of Ovarian Cancer
Chemotherapy as a treatment option for cancer has existed for decades, and has long been the standard of care and first line of treatment for almost all forms of cancer. The term is an umbrella term referring to the use of medicines to halt the growth of cancerous tumors and to kill off cancerous cells. The treatment is widely known for its effectiveness and strong side effects, which are a necessary evil on the road to long-term survival.
When cells become cancerous, they lose the ability to stop growing, and enter into a malicious state of constantly reproducing their faulty DNA. These cancerous cells can spread throughout the body and begin to crowd out healthy cells critical for life, causing the life-threatening symptoms of the disease. Chemotherapy attacks the DNA and RNA of cancerous cells, preventing them from dividing and multiplying further, and causing them to die off, which shrinks tumors and slows the growth of future cancer cells.
Unfortunately, treating cancer via chemotherapy is more like dropping a bomb on cancerous targets than sending in special forces. The medicine targets all dividing cells, including healthy cells, but is most effective on cancer cells because of the speed at which cancer cells divide. The notorious side effects of chemotherapy come from the healthy cells that die in the process, but the good news is that these healthy cells will return and regenerate, while cancer cells will not.
Doctors must prescribe chemotherapy medications and set scheduled treatments based on the type of cancer, the cells involved, the rate at which the cells divide, and the time which would be best for the administration of medicine. This last question—when is the best time to administer chemotherapy medications—has recently come into question.
Recent studies have suggested that the best regimen may depend on your genetic makeup, and that more frequent dosage is not always better.
Japanese JGOG3016 Study
One of the common chemotherapy medicines prescribed for ovarian cancer is called paclitaxel. It is also used to treat breast, lung, prostate, and bladder cancer, among others. The drug has long been approved and has long been standard practice, but some believed that the schedule of administration could be improved. A study that took place across 85 centers in Japan conducted a large scale clinical trial to determine whether or not increasing the frequency of dosage in chemotherapy would improve a person’s progression-free survival, as well as their overall survival.
Typically, a person receives one dose of paclitaxel every three weeks. Once every three weeks is the standard of care, known as first-line chemotherapy for patients who have later stage ovarian cancer. The Japanese study split the clinical trial group into two arms. The control arm of the group received the chemotherapy doses once every three weeks, as is standard. The experimental arm of the trial was put on a dose-dense treatment schedule, in which chemotherapy was administered once per week for three weeks.
A total of 631 patients participated in the study and followed through with it to the end, all with stage II-IV ovarian cancer. 312 received the dose-dense treatments, while 319 were assigned to the traditional regimen. Researchers were looking for progression-free survival, or the length of time during and after treatment that a patient survives without experiencing a worsening of existing symptoms or conditions. Overall survival typically takes place over five years, and is a simple measurement of how many people are able to survive cancer beyond five years.
The results of the study were surprisingly in favor of the dose-dense treatment schedule. By administering the chemotherapy weekly instead of once every three weeks, the progression-free survival rates and overall study rates of patients were significantly increased over what was found in the results of the control arm. With the evidence supporting higher survival rates in dose-dense treatments, the study concluded with the possibility that a weekly regimen could become the new standard of care and first-line chemotherapy for patients with ovarian cancer.
European ICON8 Study
Another study was conducted more recently in Europe, evaluating whether or not the same positive effects could be repeated in weekly administration of paclitaxel. ICON8 is a three-arm clinical trial on paclitaxel administration, with 1566 participants split into three groups and given three different dosages of the medication. The control arm received the still standard dosage—once every three weeks—while the other two experimental arms worked with varying levels of paclitaxel administered over a weekly period.
The results of the study brought a relatively new field of study into play. The primary difference between the women with ovarian cancer in JGOG3016 and ICON8 was racial. All of the women in the Japanese study were Japanese, and all of the women in the European study were European. This difference appeared to change the outcome of the studies. Contrary to the results that were clearly and accurately determined in the JGOG3016 study, the ICON8 study found there to be no benefit to administering paclitaxel on a weekly basis.
Dr. Andrew Clamp of The Christie NHS Foundation Trust and University of Manchester, UK, released a statement as study investigator, saying: “the results clearly demonstrate that, although well-tolerated, using weekly scheduling to achieve dose-intensification of paclitaxel as part of the first-line treatment of epithelial ovarian cancer does not extend progression-free survival in this population.” He concluded that due to the results of the study, weekly administration of the drug would not become the standard-of-care treatment option for the European population.
The fact still remains that the Japanese study indicated strongly that weekly administration had strong benefits over the current standard of care. Dr. Clamp confirmed that “it remains appropriate to continue to offer weekly dose-dense paclitaxel as a treatment option to Japanese women.” He supported the findings of the Japanese trial, saying that both were well-conducted trials that met their end goal. He concluded the issue by saying that “it is more likely that there are pharmacogenomics differences between these two ethnic groups that account for the different results seen.”
The Role of Pharmacogenomics
According to the genetics home reference branch of the national library of medicine, pharmacogenomics is the study of how genes affect a person’s response to drugs. It has long been known that the exact same disease can present differently in different patient groups, and that people respond to different medicines differently. Despite this knowledge, most medications are administered on a one-size-fits-all basis, with only variations in the dosage according to a doctor’s prescription.
The field is relatively new, because we are only just beginning to reach a point at which we understand how a person’s genetic makeup interacts with different pharmaceuticals. Knowledge gained from the Human Genome Project has given prescribing doctors insights into which drugs will be most effective, which drugs will have no effect, and which drugs might cause severe negative consequences.
Several other researchers—including Dr. Domenica Lorusso, of the Fondazione IRCCS National Cancer Institute of Milan—agree that the difference in results of the two major clinical trials could be genetic. Tokyo will be hosting the 5th Ovarian Consensus conference in order to discuss whether or not the dose-dense schedule will become a standard treatment option for Japanese women. With the results already made clear for European women, the standard three-week dosing of the chemotherapy drug will maintain its status as first-line treatment.
References
https://ghr.nlm.nih.gov/primer/genomicresearch/pharmacogenomics
https://www.ncbi.nlm.nih.gov/pubmed/23948349
http://chemocare.com/chemotherapy/drug-info/Paclitaxel.aspx
