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Cancer Resources > Cancer News > Cancer News from Reuters > Reuters Cancer News > 2003 > January
"Chemotherapy sensitivity testing" of biopsy predicts tumor response
Karla Gale
Last Updated: 2003-01-28 16:45:35 -0400 (Reuters Health)
NEW YORK (Reuters Health) - New techniques to evaluate tumors' responses to chemotherapeutic agents promise a future of personalized cancer management, many oncologists are beginning to believe.
One oncologist, Dr. Thomas Herzog of Washington University School of Medicine in St. Louis, calls the new technology "the wave of the future."
According to Dr. Robert Nagourney, founder of Rational Therapeutics in Long Beach, California, these assays offer more promise than do current tests for the genes expressing enzymes such as ERCC1 and XPAC, which are associated with responses to particular drugs.
"While ERCC1 is increasingly measurable, it's only one of a whole collection of enzymes that need to be assessed, such as deoxycytidine kinase and ribonucleotide reductase," he explained. "So you have to look at the interplay between enzymes--and in addition to the presence or absence, you also have to consider functional activity," Dr. Nagourney told Reuters Health.
He said that costs of testing range from $1500 to $2500. However, "cost savings alone can be substantial," when taking into account the costs of ineffective treatments and unnecessary exposure to toxicity.
Based on his lab's findings, he and associates have developed a novel regimen for refractory ovarian cancers--gemcitabine plus cisplatin (see Reuters Health report, January 21, 2003). Study results showed a correlation between ex vivo sensitivity and resistance and patient outcome.
The Gynecologic Oncology Group, multicenter non-profit organization sponsored by the National Cancer Institute, is conducting a national clinical trial of the gemcitabine plus cisplatin combination for treatment of relapsed ovarian cancer.
In an interview with Reuters Health, Dr. Herzog said, "I think that the whole idea of the assays in predicting chemosensitivity will continue to grow. As the technology improves, we will want to use it on everyone."
But he is not convinced that it is ready for prime time. "I use it only on a selected basis now." He does not advise it as front-line treatment for ovarian cancer "because we haven't proved that anything is more effective than platinum and Taxol." But as second-line treatment, he added, "with so many options available now, it can be very difficult" to decide, and assays can provide valuable information.
According to Dr. John Macdonald, Chief of Medical Oncology at St. Vincent Hospital in New York, "clearly it would be helpful to know if a drug didn't stand chance of working." He noted that chemotherapy assays have improved over the last 15 years, and "can be very effective in telling doctors which agents won't work."
But the flip side, he added, is that this approach is not as accurate for choosing drugs that will work. He believes this may be due to the drugs' inability to be delivered to the tumor or inappropriate levels of drug. He estimates that 50% to 60% of the time, when an assay predicts a drug will be effective, it is not effective in vivo.
Furthermore, he said, for such cancers as those affecting the colon, most oncologists will continue to use agents they are familiar with and for which there is reported evidence as to their efficacy.
But when that strategy does not work, he added, such assays may be more effective than "fishing for one drug after another drug that may or may not work." He believes that once more prospective evidence is available, oncologists will embrace the technology.
But not everyone is convinced. Dr. Andrew Scidman, oncologist at Memorial Sloan-Kettering Hospital in New York, told Reuters Health, "It has been hard to replicate in vivo what occurs in vitro." He said he is more driven by results of clinical trials and genomic analysis and does not use these assays.
Dr. Nagourney told Reuters Health that the National Cancer Institute is funding a prospective trial in which he and his colleagues "will document response rate, the time to progression, and overall survival, and we will correlate that information with formally measured quality of life and cost of therapy."
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