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Ovarian Cancer Survival Better With Intraperitoneal Than IV Chemo

gdpawel's picture
gdpawel
Posts: 545
Joined: May 2001

Long-term results from 2 large studies confirm the superiority of intraperitoneal (IP) administration of chemotherapy over intravenous (IV) administration after surgery in patients with advanced ovarian cancer.

"We have known for some years that intraperitoneal administration may give superior results...but it is balanced by more toxicity," said Jubilee Brown, MD, associate professor of obstetrics and gynecology at the University of Texas M.D. Anderson Cancer Center in Houston.

The exciting thing about these data "is that at 10-year follow-up, the survival effects persist," she told Medscape Medical News.

The same chemotherapy is used (cisplatin and/or carboplatin plus paclitaxel), but the dosing schedule is a little different for the 2 different routes of administration. The IP route bathes the whole abdominal cavity in chemotherapy, so the drug surrounds the ovaries and stays in place for some time; however, this also increases exposure to the drug and can result in more intense adverse effects. In addition, IP is more difficult to administer than IV; it requires different technology and a specialized skill set, she explained.

As a result, there has been "quite a lag in the oncology community in adopting intraperitoneal administration for our patients," Dr. Brown told Medscape Medical News.

The new data come from a 10-year follow-up of patients taking part in Gynecologic Oncology Group (GOG) trials 114 and 172. They were presented at the Society of Gynecologic Oncology (SOG) 44th Annual Meeting on Women's Cancer, being held in Los Angeles, California.

After the 876 women from the 2 trials had undergone primary surgical cytoreduction, they were randomized to receive either IP or IV chemotherapy. There was a significant improvement in median overall survival with IP administration, compared with IV administration (61.8 vs 51.4 months; P = .0048).

"This is big news," said Dr. Brown, who acts as a spokesperson for the SGO. The committee reviewing the abstracts for the meeting felt that this study is the one that is most likely to change clinical practice and have an impact on patients, she noted.

The other finding is that "more is better, but even some cycles are useful," she said. Patients who completed 5 or 6 cycles of IP therapy had a 5-year overall survival of 59%, compared with 33% for those who completed 3 or 4 cycles and 18% for those who completed 1 or 2 cycles (P < .001).

The data were presented by Devansu Tewari, MD, director of gynecologic oncology for the Southern California Permanente Medical Group in Orange County, and assistant professor of obstetrics and gynecology at the University of California, Irvine.

"There is no question that IP therapy should be much more widely offered," Dr. Tewari said. He described IP therapy as a "potential life-saver," and added that "too many women do not receive an explanation of the advantages and disadvantages."

However, Dr. Tewari cautioned that IP therapy needs to be administered by a physician who has expertise in the treatment and can best manage the risks and adverse effects.

Selecting Patients for IP Treatment

In their analysis, Dr. Tewari and colleagues found that younger and healthier patients completed more cycles of IP.

Another analysis of data from one of the trials (the GOG 172 study) suggests that decreased expression of the BRCA1 protein could be used as a biomarker to identify patients who are most likely to respond to IP therapy. That analysis, led by Thomas Krivak, MD, from Magee-Womens Hospital of UPMC in Pittsburgh Pennsylvania, was published online March 5 in the British Journal of Cancer.

Of the 393 patients analyzed by Dr. Krivak's team, 204 had tumors with normal BRCA1 expression and 189 had tumors with aberrant BRCA1 expression.

The survival advantage of IP chemotherapy was only seen in the subset of patients with aberrant BRCA1 expression. In this subgroup, median overall survival was 84 months with IP and 47 months with IV (P = .0002).

There was no significant survival difference for IP and IV administration in patients with normal BRCA1 expression (58 vs 50 months; P = .818).

Aberrant BRCA1 expression is an independent prognostic factor for better survival in women randomized to IP therapy (hazard ratio, 0.67; P = .032), Dr. Krivak and colleagues conclude.

"This research should allow us to target a particular group of ovarian cancer patients and give them an improved outlook by making a very simple change to their treatment," Dr. Krivak said in a statement.

Dr. Brown said that this is early evidence showing that this subgroup of patients might respond better, but it pushes us "to consider IP." However, she added that it is too early "to make that a firm recommendation."

"This is an important observation that may substantially influence clinical management — specifically, the decision to deliver or not deliver IP chemotherapy in ovarian cancer," said Maurie Markman, MD, national director for medical oncology at the Cancer Treatment Centers of America, clinical professor at Drexel University College of Medicine in Philadelphia, and Medscape video blogger for Markman on Oncology.

"It is critical to note that this has nothing to do with BRCA mutations," Dr. Markman noted. "Rather, the research deals with the amount of BRCA protein [present in the tumor]."

It looks like the BRCA protein is involved in DNA repair, he explained. When levels of this protein are low, the cancer appears to be unable to repair the additional damage that results from the more dose-intensive approach of IP administration. However, with high levels of the protein, the additional damage can be repaired, so for patients with high levels of BRCA protein in their tumor, there is no added benefit from the IP approach, he said.

Testing tumor tissue for BRCA protein levels is not currently routine, he told Medscape Medical News, "but it is my understanding that this would not be difficult to implement."

Br J Cancer. Published online March 5, 2013.

Society of Gynecologic Oncology (SOG) 44th Annual Meeting on Women's Cancer: Abstract 6. Presented March 9, 2013.

Citation: Ovarian Cancer Survival Better With Intraperitoneal Than IV Chemo. Medscape. Mar 11, 2013.

http://www.nature.com/bjc/journal/vaop/ncurrent/full/bjc201370a.html

gdpawel's picture
gdpawel
Posts: 545
Joined: May 2001

Intraperitoneal Chemotherapy Gives Ovarian Cancer Patients Better Chance Of Survival

Patients with advanced ovarian cancer who undergo intensive treatment with chemotherapy that bathes the abdomen are significantly more likely to live longer than those who receive standard intravenous (IV) chemotherapy, according to a study that analyzed long-term follow-up from two landmark Gynecologic Oncology Group (GOG) trials comprising 876 patients. Results of the study are being presented at the Society of Gynecologic Oncology (SGO) Annual Meeting on Women's Cancer in Los Angeles, March 9-12.

Women who receive the treatment in the form of intraperitoneal, or IP chemotherapy are 17 percent more likely to survive longer than those who have IV chemotherapy, according to the analysis, which had a median follow-up of more than 10 years. Median survival was more than five years (62 months) for patients in the IP group and about four years (51 months) for patients in the IV group. Median is defined as the number separating the upper and lower half of a study population.

The findings also suggest women who complete most or all of the recommended six cycles of IP therapy are likely to live longer than women who complete four or fewer cycles. After five years, 59 percent of patients who completed five or six cycles of IP therapy were alive, compared to 33 percent of those who completed three or four cycles and 18 percent of those who completed one or two cycles. Patients who are unable to receive the full six cycles of IP therapy typically transition to IV chemotherapy for the remaining cycles.

"Too many women do not receive an explanation about the advantages and disadvantages of IP therapy and that it could be a potential life saver," said Devansu Tewari, MD, Director of Gynecologic Oncology for the Southern California Permanente Medical Group in Orange County, Calif., of Kaiser Permanente and Assistant Professor of Obstetrics and Gynecology at the University of California, Irvine School of Medicine. "But there is also a caution that it should be administered by a physician who has expertise in the treatment and can best manage the risks and side effects."

Every year, more than 22,000 women are diagnosed with ovarian cancer and more than 15,000 die of the disease. In standard IV chemotherapy, the drugs are infused into the bloodstream and throughout the body, whereas IP treatment directs the chemotherapy to the abdomen. This not only places a high concentration of cancer-killing drugs where they are needed, but the chemotherapy agents are absorbed more slowly, providing more exposure to the medicine. IP is recommended by the National Cancer Institute for women who have had optimal surgery.

Because IP therapy is more rigorous, some of the side effects are also more intense, such as numbness in the hands and feet and abdominal pain, and some women are unable to complete the suggested six cycles of therapy. Researchers found younger, healthier patients were more likely to complete more cycles of IP.

Funded by the National Cancer Institute, the Gynecologic Oncology Group comprises experts in the field, from gynecologic oncologists to nurses to scientists, who are committed to maintaining the highest standards in clinical trials. The GOG focuses its research on women with pelvic malignancies, such as cancer of the ovary, uterus and cervix.

"There is no question IP therapy should be much more widely offered, and advanced ovarian cancer patients should consult with gynecologic oncologists or medical oncologists with experience in this cancer who have the expertise to determine the best therapy," said Dr. Tewari. "At the very least, these women should be treated by someone who has experience with IP therapy issues and knowledge of whether she would be a good candidate."

Citation: Society of Gynecologic Oncology (SGO). "Bathing Abdomen In Chemotherapy Gives Ovarian Cancer Patients Better Chance Of Survival." Medical News Today. MediLexicon, Intl., 9 Mar. 2013

gdpawel's picture
gdpawel
Posts: 545
Joined: May 2001

In 2006, Dr. Deborah Armstrong's study was published on this protocol and many doctors thought the results would change the field forever. It compared standard intravenous chemotherapy with intraperitoneal chemotherapy. The test regimen was highly toxic, and not all patients could tolerate it, with only 42% of women being able to finish the rather arduous trial. But Armstrong had the most definitive results. 

Why hasn't IP therapy caught on? Dr. Armstrong told New York Times that part of the reason may involve money. With IP chemotherapy, patients also need a lot of intravenous fluids, which means unusually long treatment sessions. Oncologists are paid for treatments, not for time, so for those in private practice, long sessions can eat away at income. “You don’t make a lot of money with somebody in the chair getting IV fluids,” Dr. Armstrong said. “Chair time is money."

The issue about "chair time" is similar to the way a restaurant owner doesn't want customers to linger for a long time over a meal, but instead wants them to eat, drink, pay their bill and free up the table for the next customer. Some chemotherapy treatments require the patient to remain in the oncologist's chemotherapy chair for many hours. Other treatments are in and out in a matter of minutes. NCI-designated cancer centers want to free up chairs for their clinical trial students.

Intraperitoneal chemotherapy improving the chances of survival in ovarian cancer could be an indication of the "Right Therapy" but the "Wrong Drugs." 

The hallmark of cancer is heterogeneity. Not just many types of cancer, but many subtypes of cancer within a given type. The biologies are very different and the response to given drugs is very different. 

The hallmark of cancer treatment is heterogeneity. There are hundreds of FDA approved cancer drugs. All of these drugs tend to be partially effective, and even then, in only a minority of cases, and often for only a short duration of time. 

The single most neglected area of cancer research has been the development of methods and technologies to be "matchmakers" between individual cancer with individual cancer treatment. 

The single most neglected area of cancer treatment has been the unwillingness to utilize the matchmaker technologies which have already been developed and available. These technologies involve studies of cancer cell responses to drug exposure in cell culture systems "outside" of the patient's body, before they are put "into" the patient's body.

http://cancerfocus.org/forum/showthread.php?t=253

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