WHEN the US National Cancer Institute (NCI) recently issued an announcement encouraging a method of treating women with advanced ovarian cancer, the world’s medical community looked up.
It is said to be rare that the NCI makes an announcement like that, which is a testament to the significant life-advancing benefits of this new treatment method.
“In the whole history of NCI, they have only issued about five or six clinical announcements,” says Dr Suresh Kumarasamy, a consultant obstetrician and gynaecologist in a private hospital in Penang.
The last time they issued an announcement was in 1999 regarding concurrent chemo-radiation in cervical cancer, he adds.
So what exactly is all the fuss with the recent announcement?
In the January 5, 2006 issue of the New England Journal of Medicine, an article was published describing a new method of administering chemotherapy intraperitoneally (delivering chemotherapy directly into the abdomen).
“The survival benefits shown in this paper is one of the largest benefits ever observed for a new therapy in gynaecological oncology,” explains Dr Suresh, who also sub-specialises in gynaecological oncology.
The improvement in survival is particularly significant in ovarian cancer, a disease that claims a great number of victims because it is often detected at a late stage.
What, who, why?
Ovarian cancer is the fifth most common cancer among Malaysian women (according to the Second Report of the National Cancer Registry, 2003).
“There are two main types of ovarian cancer. Epithelial ovarian cancer is the most common type that accounts for about 90% of cases,” says Dr Suresh.
The other type of ovarian cancer, germ cell tumours, are less common.
There are no known risk factors for the majority of ovarian cancer cases. However, family history is important as about five to 10% of the cancers result from a hereditary predisposition.
“Also, women who are known to carry the genes associated with ovarian cancer – the BRCA1 and BRCA 2 genes – are at higher risk of ovarian and breast cancer,” adds Dr Suresh.
Ovarian cancer is a dreaded disease because it is often diagnosed at a late stage. “About 70% of women are diagnosed at stage three or four”, which means that the overall five-year survival rate is only 30%, says Dr Suresh.
By the time the cancer is diagnosed, the tumour has often spread beyond the ovaries to neighbouring organs like the uterus, bowel and other areas within the abdominal cavity.
The good news is that there is a high survival rate for cancer that is diagnosed early and treated correctly.
In ensuring an accurate diagnosis, the doctor will take the woman’s medical history and perform the necessary clinical examinations, which include an abdominal examination as well as a pelvic examination. Other tests including ultrasound scans, tumour marker tests or even CT scans will then be carried out, depending on the individual patient. It is important that a careful and thorough assessment is carried out before embarking on surgery.
Treating ovarian cancer
If the doctor suspects cancer, the patient will be recommended to go for surgery, for an operation called a laparatomy.
The purpose of the operation is to determine the stage of the cancer as well as to remove tissue that contains the cancer.
Usually, the surgeon will remove the ovarian tumour together with the ovaries, the uterus and the omentum (the fat that hangs from the stomach and large intestines). The aim of the surgery is to remove as much of the tumour as possible.
The removal of the tumour is called “debulking”, which plays a very important role in the patient’s survival.
“There is a very close relationship between the amount of tumour left behind after surgery (called residual tumour) and the survival of the patient. Less or no residual tumour equals better survival,” Dr Suresh explains.
It is important that this complex surgery is carried out by a surgeon with the necessary skills, training and experience in managing this disease.
In their recent clinical announcement, the National Cancer Institute emphasised that “effective surgical debulking is critical to long-term survival of ovarian cancer. Women undergoing surgery for presumed ovarian cancer therefore should undergo surgery by a gynaecological oncologist or surgical team with experience in the staging and cytoreduction (debulking) of ovarian cancer.”
A study (Jonor et al, 1999) looking at the outcome of all patients with ovarian cancer in Scotland over a number of years found that there was a lower death rate when the surgery was carried out by a gynaecological-oncologist, compared to surgery by a general gynaecologist.
One only has to look at the number of steps involved in a laparatomy to understand its complexities. Before the actual debulking, the surgeon has to first remove the ascites (fluid within the abdominal cavity), perform a peritoneal wash, and examine the abdominal cavity to plan the surgery and subsequent treatment.
If surgery is unable to remove all the cancer cells, chemotherapy may be needed to decrease the risk of recurrence and cure the patient, or at least prolong survival.
Patients with very early cancer (stage 1A, Grade 1) need not be treated with chemotherapy, but those with more advanced stage cancer will need it.
Chemotherapy uses drugs to stop the growth of cancer cells, either by killing the cancer cells or by stopping the cells from dividing, multiplying and spreading. Usually, the patient will need to go for six courses of chemotherapy every three to four weeks.
Commonly used drugs for ovarian cancer chemotherapy are carboplatin or a combination of carboplatin and paclitaxel.
The new approach
Chemotherapy in ovarian cancer has been given a boost with the results of a study published in the New England Journal of Medicine on January 5, 2006.
This study was carried out by the Gynaecologic Oncology Group (GOG), an American gynaecological cancer research group that has been studying methods of treatment of various gynaecological cancers for many years.
This study hailed the advantages of a new method of administering chemotherapy. Called the intraperitoneal (IP) chemotherapeutic approach, this is a method where “the drugs are directly administered into the abdomen,” explains Dr Suresh.
Unlike conventional chemotherapy that delivers drugs into a vein with a drip, IP therapy delivers the drugs via a special intraperitoneal port into the abdomen.
In the study, 429 women with stage three optimally debulked ovarian cancer were divided into two groups; one group was given conventional IV chemotherapy, and the other group a combination of IV and IP chemotherapy.
The women who received combination IV and IP therapy survived 16 months longer than the group who received conventional IV therapy, “one of the most remarkable improvements in survival in recent times,” remarks Dr Suresh.
“The (chemotherapy) drugs appear more effective in killing cancer cells in the peritoneal cavity, where the cancer is likely to spread or recur first.
He reasons that the IP method works better “because the chemotherapy drugs are at a higher concentration and remain active in the abdominal area for longer when compared to IV therapy. The drugs slowly leave the peritoneal cavity and enter the circulation, resulting in the chemotherapy drug remaining in the system and acting for a longer period of time.”
Surprisingly, IP therapy is nothing new in the field of oncology.
“IP therapy is not a new treatment approach, but it has not been widely accepted as the gold standard for women with ovarian cancer,” says lead investigator of the study Deborah Armstrong, medical oncologist and an associate professor at Johns Hopkins Kimmel Cancer Center in Baltimore, US, in the announcement posted on the NCI website.
“Now we have firm data showing that we should use a combination of IP and IV chemotherapy in most women with advanced ovarian cancer who have had successful surgery to remove the bulk of their tumour,” Armstrong is quoted as saying in the website.
While Dr Suresh lauds the impressive results of the study, he also adds that it is not suitable for everyone.
“It is useful only for patients with minimal or no residual tumour, hence the importance of adequate debulking by an experienced surgeon,” he elaborates.
Furthermore, there are more side effects with the IP approach, and possible complications with the port, including blockages and leaks.
“The risk of infection and fever is higher ? and patients are more likely to have side effects like abdominal pain, nausea, vomiting, blood toxicity, metabolic side effects as well as neurological (nerve) toxicity,” says Dr Suresh.
In the study, however, the toxicities were generally short-term and manageable. Dr Suresh also points out that one way to minimise complications with the port is to insert it during the initial surgery to remove the tumour.
“Some patients may be prepared to put up with the potential (short-term) side effects of IP chemotherapy” if their survival rate will be improved, he says.
“It is an option in suitable patients. I always discuss available options with patients, with the pros and cons of each approach,” Dr Suresh concludes.
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