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A phase III trial has reported gemcitabine (Gemzar) was shown not to be superior to pegylated liposomal doxorubicin for patients with recurrent ovarian cancer.
Neither time to progression nor overall survival was longer with pegylated liposomal doxorubicin (Doxil/PLD) in the 153-patient study. PLD was associated with significantly less severe toxicity, however, and significantly better quality of life scores, lead investigator Dr. Gabriella Ferrandina reported on behalf of the Multicentre Italian Trials in Ovarian Cancer (MITO) group.
The researchers randomized 76 women to 40 mg/m² of PLD over 1 hour on day 1 every 4 weeks, and 77 women to 1,000 mg/m² of gemcitabine over 30 minutes on days 1, 8, and 15 every 4 weeks. All patients had relapsed within 12 months from completion of primary platinum/paclitaxel treatment or had evaluable lesions. The average age was 63 years in both groups.
The number of delayed cycles was significantly more with gemcitabine than PLD (32 vs.13); the number of reduced cycles was similar (22 vs. 24). The study's primary end point, median time to progression, was 16 weeks with PLD and 20 weeks with gemcitabine (P = .4).
Median overall survival also was similar: 55 weeks in the PLD arm and 50 weeks in the gemcitabine arm (P = .17). Longer follow-up is needed to evaluate this secondary outcome fully, said Dr. Ferrandina, Catholic University, Rome.
Three patients on PLD had a complete response, compared with two on gemcitabine. In addition, 8 patients on PLD and 15 on gemcitabine had partial responses. Among evaluable patients, overall response was 15.9% with PLD and 28.3% with gemcitabine.
Among those treated with PLD, six patients had grade 3/4 leukopenia and five had grade 3/4 neutropenia. In contrast, 15 patients treated with gemcitabine had grade 3/4 leukopenia and 15 grade 3/4 neutropenia. The difference was statistically significant for both toxicities (P less than .05), the investigators reported. Grade 3/4 pruritic papular eruptions occurred in four patients given PLD and none treated with gemcitabine (P = .06).
Global quality of life scores were significantly higher among patients treated with PLD (P less than .05). The difference may reflect an easier dosing schedule for PLD, but still cannot be ignored, said discussant Dr. William P. McGuire, director of the Weinberg Cancer Institute, Franklin Square Hospital Center, Baltimore.
Overall, the two drugs probably are equivalent in activity in platinum-resistant disease, although their toxicity profiles are different, Dr. McGuire said. Gemcitabine is approved in the United States in combination with carboplatin for advanced ovarian cancer that has relapsed at least 6 months after completion of platinum-based therapy. Doxil is approved for ovarian cancer that has progressed or recurred after prior platinum-based therapy.
"The decision regarding choice of drugs should be based on a discussion with the patient, and depends more on the acceptance of specific toxicities than on real differences in terms of benefit," Dr. McGuire said.
Ferrandina G. et al. A randomized phase III study of gemcitabine (GEM) versus pegylated liposomal doxorubicin (PLD) in progressive/recurrent ovarian cancer (OC). Abstract LBA5506.
Commentary |
Ferrandina et al. randomized patients with recurrent ovarian carcinoma who relapsed within 12 months of completing first-line paclitaxel/platinum to either pegylated liposomal doxorubicin (PLD) or gemcitabine regimens. The study was designed to show a 58% improvement in time to progression with gemcitabine from a median of 12 weeks to 19 weeks. Overall response, median time to progression, and median survival were not statistically different. Quality of life was statistically superior with PLD. Gemcitabine produced more myelosuppression; PLD more hand-foot syndrome. Rational conclusions are that both agents have activity in platinum-resistant/refractory recurrent ovarian carcinoma and that neither agent has a major advantage over the other. Since most patients in this setting receive multiple single-agent therapies, gemcitabine and PLD will continue to have important roles in the management of these resistant/refractory patients. — J. Tate Thigpen, M.D.
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