Pegylated Liposomal Doxorubicin clinical trial data

This is an interesting study regarding recurrence treatment:

"Carboplatin/Pegylated Liposomal Doxorubicin Is as Effective as Carboplatin/Paclitaxel in Recurrent Ovarian Cancer
Elsevier Global Medical News. 2009 Jul 8, K Wachter

ORLANDO (EGMN) - The doublet of carboplatin plus pegylated liposomal doxorubicin extends progression-free survival as effectively as the standard treatment of carboplatin plus paclitaxel in women with platinum-sensitive recurrent epithelial ovarian cancer, and may even be superior, based on the results of the open-label phase III CALYPSO trial involving almost 1,000 women.

Median progression-free survival reached 11.3 months for women treated with carboplatin plus pegylated liposomal doxorubicin (PLD) and 9.4 months for women given carboplatin plus paclitaxel (Taxol) (hazard ratio, 0.82; P for noninferiority less than .001; P for superiority = .005), Dr. Eric Pujade-Lauraine reported on behalf of the Gynecologic Cancer Intergroup (GCIG) at the annual meeting of the American Society of Clinical Oncology. Median follow-up was 22 months.

"These results will change practice, as [carboplatin/PLD] offers an evidence-based option for patients with platinum-sensitive recurrent ovarian cancer," he said.

It may be too soon to call carboplatin/PLD the superior treatment, cautioned Dr. Jonathan Ledermann, an oncologist at University College London, who was invited to discuss the study. "We can, without a doubt, say that noninferiority - which was the primary end point of this study - has been confirmed, but can one say that [carboplatin/PLD] is a superior treatment? There are differences in the duration of treatment [and] more early discontinuation and/or hypersensitivity reactions, and the differences in progression-free survival emerge after 6 months," he said.

The study randomized 508 women with ovarian cancer in late relapse to receive carboplatin/paclitaxel and 466 women to receive carboplatin/PLD. They had to have had previous taxane exposure and disease progression more than 6 months after first- or second-line platinum-based therapy.

The control regimen consisted of carboplatin AUC (area under the curve) 5 plus 175 mg/m² intravenous paclitaxel on day 1 of a 21-day cycle, for six cycles. In the experimental arm, women received carboplatin AUC 5 plus 30 mg/m² intravenous PLD on day 1 of a 28-day cycle, for six cycles. Most patients (88% and 83% in the experimental and control arms, respectively) had received one previous line of chemotherapy.

Notably, median treatment duration was longer in the PLD arm (21 vs. 16 weeks). "This difference was not only due to the fact that the length of the cycle was different between the two arms, but also because a higher percentage of patients in the carboplatin/PLD arm [was able to achieve] the six planned cycles," said Dr. Pujade-Lauraine of the Université Rene Descartes and the Hôpital Hôtel-Dieu, both in Paris. In all, 85% of patients in the PLD arm had at least six cycles vs. 78% of the control arm.

Among hematologic toxicities, grade 3/4 neutropenia was significantly more common in the control arm, and grade 3/4 thrombocytopenia in the PLD arm. "Overall, the clinical consequences of these hematologic toxicities were low in both arms," he said.

Nonhematologic toxicities showed significant differences, mostly favoring PLD. Notably, grade 2 alopecia was much more common in the control arm (84% vs. 7%; P less than .001), as were grade 2 and grades 3-5 neuropathy and grade 2 arthralgia/myalgia. Grade 2 nausea/vomiting, hand-foot syndrome, and mucositis were significantly more common in the PLD arm.

"We were surprised to see that there was a lower rate of early treatment discontinuation due to toxicity in the carboplatin/PLD arm," noted Dr. Pujade-Lauraine. In all, 27 patients in the experimental arm discontinued treatment early because of toxicity, compared with 73 in the control arm.

This appears to be related to an unexpected finding: Hypersensitivity to carboplatin occurred significantly more frequently when it was combined with paclitaxel than when it was combined with PLD. "This is an important finding with clinical implications for all of you who treat patients with ovarian cancer, and for women," he said.

Dr. Ledermann urged attendees to keep in mind that the overall survival data are immature. "Should we be making decisions about changing to carboplatin/liposomal doxorubicin without any information at all on the survival data?" he asked.

Schering-Plough Corp., which sponsors PLD as Caelyx outside the United States, was among the trial's many sponsors and collaborators. The study authors reported no relevant financial relationships. Dr. Ledermann disclosed that he is on ad hoc advisory boards for Schering-Plough and four other drug companies. "