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Cancer Resources > Cancer News > Cancer News from Reuters > Reuters Cancer News > 2003 > January
Gemcitabine-cisplatin regimen successful for relapsed ovarian cancer
Karla Gale
Last Updated: 2003-01-21 17:04:33 -0400 (Reuters Health)
NEW YORK (Reuters Health) - Using ex vivo drug sensitivity profiles, researchers have identified a novel chemotherapy regimen effective in treating relapsed, multidrug-resistant ovarian cancer. Two separate trials in which gemcitabine and cisplatin were administered sequentially on the same days are reported in the January issue of Gynecologic Oncology.
Dr. Robert A. Nagourney, of Rational Therapeutics Inc. in Long Beach, California, and associates have developed an assay that measures drug-induced tumor cell apoptosis rather than cell proliferation-based endpoints. The assay revealed high degrees of cytotoxic activity and synergy for the gemcitabine/cisplatin combination in ovarian cancer specimens.
Therefore, the research team treated 27 previously treated ovarian carcinoma patients with cisplatin 30 mg/m² plus gemcitabine 750 mg/m² on days 1 and 8 of several 21-day cycles. Twenty patients required dose reductions after the first treatment cycle.
Nineteen (70%) patients responded, including 7 (26%) in whom response was complete and who have survived for 13 to 51 months of follow-up. Among partial responders, the median time to progression was 7.9 months.
"Ex vivo results correlated with response, time to progression, and survival, remaining significant when adjusted for platin-resistance and number of prior therapies," Dr. Nagourney's group writes.
These clinicians note that 14 subjects had cancer that met criteria for platinum resistance. They suggest that gemcitabine depletes intracellular nucleosides, which are then unable to repair cisplatin-DNA adducts, thus overcoming platinum resistance.
In the second paper, Dr. Peter G. Rose and associates at Case Western Reserve University in Cleveland used a similar treatment regimen for 33 patients with refractory ovarian cancer and 3 with refractory peritoneal carcinomas, all of which were resistant to platinum and paclitaxel treatment.
There were 11 partial responders and 4 complete responders. "This experience provides clinical support for the synergism of the combination gemcitabine and cisplatin which had been demonstrated in vitro," they write.
Both groups reported significant toxicities, including hematologic abnormalities, nausea and vomiting, peripheral neuropathy, and ototoxicity. However, Dr. Nagourney's group maintains that toxicities are manageable with dose modifications.
In an interview with Reuters Health, Dr. Rose noted that clinicians can now predict a patient's response to platinum-based chemotherapy by looking at the tumor's expression of the ERCC1 enzyme. Hence, patients likely to benefit from combining gemcitabine with cisplatin can be identified prior to initiating treatment.
Since submitting their paper in April last year, Dr. Rose said, "We've continued to use this regimen, but we're also studying the combination of gemcitabine with carboplatin, and looking at different schedules for carboplatin."
Gynecol Oncol 2003;88:17-21,35-39.
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