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Intraperitoneal treatment lengthens survival in ovarian cancer
Newsdesk
In January, 2006, the US National Cancer Institute (NCI) recommended that eligible women with advanced ovarian cancer should be treated with chemotherapy via the intraperitoneal route as well as intravenously. The NCI based its decision on the results of several clinical trials and timed its announcement to coincide with the publication of the most recent phase III trial, done by the Gynecologic Oncology Group (GOG), in which intraperitoneal chemotherapy was shown to lengthen survival by an average of 16 months. Deborah Armstrong (Johns Hopkins Kimmel Cancer Center, Baltimore, MD, USA) and colleagues tested two chemotherapy regimens in 415 women whose stage III ovarian cancer had been optimally debulked. Surgery was radical, and 30% of patients needed regimental bowel resections. The first group received paclitaxel on day 1 and cisplatin on day 2, by the intravenous route, every 3 weeks for six cycles. The second group received intravenous paclitaxel on day 1, but were given cisplatin on day 2 and an extra dose of paclitaxel on day 8 via a peritoneal catheter. Although this group was set to receive this 3-week repeating programme for six cycles, many patients could not tolerate intraperitoneal chemotherapy—only 43% of this group completed all six cycles by this route. Many patients had to switch to intravenous treatment because of catheter problems, toxic effects from the high dose of cisplatin, or other difficulties such as abdominal pain. Despite these issues, average time to progression in women who received intraperitoneal chemotherapy was 23·8 months versus 18·3 months for the intravenous-only group. Overall survival also increased: patients given intraperitoneal chemotherapy survived an average of 65·6 months, compared with 49·7 months in the intravenous group (N Engl J Med 2006; 354: 34–43). “The results of the GOG172 trial of intraperitoneal chemotherapy are http://oncology.thelancet.com Vol 7 February 2006
undoubtedly important because of the survival benefit. The results and the NCI clinical announcement, which draws on supporting data from previous trials, will arouse international interest from professionals and patients”, comments Henry Kitchener, St Mary’s Hospital, University of Manchester, UK. In an accompanying comment, Stephen Cannistra (Harvard Medical School, Boston, MA, USA) says that to be successful this technique requires optimum tumour debulking, since drugs delivered intraperitonealy penetrate only a few millimetres beneath the tumour surface. “Patients with no residual mass greater than 1 cm in diameter are reasonable candidates for this approach”, he stresses. Sean Kehoe (John Radcliffe Hospital, Oxford, UK) notes that specialist experience is needed: “Gynaecological oncologists have a higher rate of success compared with general gynaecologists”, he says. The same group investigated reasons that patients discontinue intraperitoneal chemotherapy, and published their findings in Gynecol Oncol (2006; 100: 27–32). “We found a clear association between rectosigmoid colon resection and the inability to initiate intraperitoneal therapy but, for those that completed some early cycles, catheter choice, timing of insertion, and previous surgery could all have played a part in whether they continued”, says lead author Joan Walker (University of Oklahoma, OK, USA). “To adopt intraperitoneal chemotherapy more widely, a period will be required to permit individuals to gain some experience, but this should not be an insurmountable problem, and I would have thought that intraperitoneal [treatment] could eventually be widely used”, notes Kehoe. Several groups are committed to education of physicians and nurses about this technique and the Society of Gynecologic Oncologists have placed tools on their website, explains Cannistra. “Every oncology practice, whether it is
© Profs PM MOTTA and S Makabe/Science Photo Library
Intraperitoneal treatment lengthens survival in ovarian cancer
New recommendation for treating ovarian cancer
located in the USA or elsewhere, will have to decide whether they have the resources, or wish to develop the resources, to provide this therapy for appropriate patients. If they do not, it would be reasonable for them to consider referring appropriate patients to centres where intraperitoneal chemotherapy is more routinely administered”, he says. The difficulties encountered with tolerance of intraperitoneal therapy will require further trials. Kitchener thinks the UK and other countries will now investigate which regimen can best maintain the survival benefit, but lessen short-term toxic effects in clinical trials. Phillipe Morrice, Institut Gustave Roussy, Villejuif, France, says there are two obvious approaches: changing the dose or changing the drug used intraperitoneally and studying the optimal procedure for delivery (different surgical procedures or catheter devices). Kitchener’s group plan to develop a clinical trial to compare two intravenous and intraperitoneal regimens, particularly for tolerability and toxic effects. “This will also enable a broader skill base to be developed within the rigours of a clinical trial. In the future, we will also need to understand more clearly exactly why intraperitoneal chemotherapy appears so effective”, he concludes.
Kathryn Senior 107
In January, 2006, the US National Cancer Institute (NCI) recommended that eligible women with advanced ovarian cancer should be treated with chemotherapy via the intraperitoneal route as well as intravenously. The NCI based its decision on the results of several clinical trials and timed its announcement to coincide with the publication of the most recent phase III trial, done by the Gynecologic Oncology Group (GOG), in which intraperitoneal chemotherapy was shown to lengthen survival by an average of 16 months. Deborah Armstrong (Johns Hopkins Kimmel Cancer Center, Baltimore, MD, USA) and colleagues tested two chemotherapy regimens in 415 women whose stage III ovarian cancer had been optimally debulked. Surgery was radical, and 30% of patients needed regimental bowel resections. The first group received paclitaxel on day 1 and cisplatin on day 2, by the intravenous route, every 3 weeks for six cycles. The second group received intravenous paclitaxel on day 1, but were given cisplatin on day 2 and an extra dose of paclitaxel on day 8 via a peritoneal catheter. Although this group was set to receive this 3-week repeating programme for six cycles, many patients could not tolerate intraperitoneal chemotherapy—only 43% of this group completed all six cycles by this route. Many patients had to switch to intravenous treatment because of catheter problems, toxic effects from the high dose of cisplatin, or other difficulties such as abdominal pain. Despite these issues, average time to progression in women who received intraperitoneal chemotherapy was 23·8 months versus 18·3 months for the intravenous-only group. Overall survival also increased: patients given intraperitoneal chemotherapy survived an average of 65·6 months, compared with 49·7 months in the intravenous group (N Engl J Med 2006; 354: 34–43). “The results of the GOG172 trial of intraperitoneal chemotherapy are http://oncology.thelancet.com Vol 7 February 2006
undoubtedly important because of the survival benefit. The results and the NCI clinical announcement, which draws on supporting data from previous trials, will arouse international interest from professionals and patients”, comments Henry Kitchener, St Mary’s Hospital, University of Manchester, UK. In an accompanying comment, Stephen Cannistra (Harvard Medical School, Boston, MA, USA) says that to be successful this technique requires optimum tumour debulking, since drugs delivered intraperitonealy penetrate only a few millimetres beneath the tumour surface. “Patients with no residual mass greater than 1 cm in diameter are reasonable candidates for this approach”, he stresses. Sean Kehoe (John Radcliffe Hospital, Oxford, UK) notes that specialist experience is needed: “Gynaecological oncologists have a higher rate of success compared with general gynaecologists”, he says. The same group investigated reasons that patients discontinue intraperitoneal chemotherapy, and published their findings in Gynecol Oncol (2006; 100: 27–32). “We found a clear association between rectosigmoid colon resection and the inability to initiate intraperitoneal therapy but, for those that completed some early cycles, catheter choice, timing of insertion, and previous surgery could all have played a part in whether they continued”, says lead author Joan Walker (University of Oklahoma, OK, USA). “To adopt intraperitoneal chemotherapy more widely, a period will be required to permit individuals to gain some experience, but this should not be an insurmountable problem, and I would have thought that intraperitoneal [treatment] could eventually be widely used”, notes Kehoe. Several groups are committed to education of physicians and nurses about this technique and the Society of Gynecologic Oncologists have placed tools on their website, explains Cannistra. “Every oncology practice, whether it is
© Profs PM MOTTA and S Makabe/Science Photo Library
Intraperitoneal treatment lengthens survival in ovarian cancer
New recommendation for treating ovarian cancer
located in the USA or elsewhere, will have to decide whether they have the resources, or wish to develop the resources, to provide this therapy for appropriate patients. If they do not, it would be reasonable for them to consider referring appropriate patients to centres where intraperitoneal chemotherapy is more routinely administered”, he says. The difficulties encountered with tolerance of intraperitoneal therapy will require further trials. Kitchener thinks the UK and other countries will now investigate which regimen can best maintain the survival benefit, but lessen short-term toxic effects in clinical trials. Phillipe Morrice, Institut Gustave Roussy, Villejuif, France, says there are two obvious approaches: changing the dose or changing the drug used intraperitoneally and studying the optimal procedure for delivery (different surgical procedures or catheter devices). Kitchener’s group plan to develop a clinical trial to compare two intravenous and intraperitoneal regimens, particularly for tolerability and toxic effects. “This will also enable a broader skill base to be developed within the rigours of a clinical trial. In the future, we will also need to understand more clearly exactly why intraperitoneal chemotherapy appears so effective”, he concludes.
Kathryn Senior 107