LEICESTER, EnglandPegylated liposomal doxorubicin (Doxil/Caelyx)
performs as well as paclitaxel (Taxol) in the treatment of relapsed ovarian
cancer, according to a clinical trial that was stopped when paclitaxel won
approval for first-line treatment in Europe. The trial was nearly forgotten,
but then a second look at the results suggested that pegylated liposomal
doxorubicin might be preferred for some patients who have musculoskeletal
disorders or are troubled by the prospect of developing alopecia as a side
effect (ASCO abstract 808).
Kenneth J. O’Byrne, MD, of the Leicester Royal Infirmary in Leicester,
England, and his colleagues reached this conclusion after they resurrected
the open label, randomized study conducted in Europe between June 1997 and
August 1999. The trial ran parallel to a trial that found pegylated
liposomal doxorubicin to be as effective as topotecan (Hycamtin) in relapsed
ovarian cancer, Dr. O’Byrne said. Earlier studies had shown the pegylated
liposomal form of doxorubicin to be more effective than conventional
doxorubicin against this disease.
Akin to Archaeologists
A total of 214 patients had been enrolled at 33 sites in Europe. All
patients had taxane-naïve ovarian cancer that relapsed following the
failure of first-line platinum-based chemotherapy. Half received 50 mg/m² of
pegylated liposomal doxorubicin as a 1-hour infusion every 4 weeks, and half
were given 175 mg/m² of paclitaxel over 3 hours every 3 weeks.
"The primary end point was time to progression, and what we wanted
to look for was a lack of inferiority of Caelyx to paclitaxel. The secondary
endpoints were survival, response rate and safety," Dr. O’Byrne said,
comparing himself and his colleagues to archaeologists as they reviewed the
original data with help from Ortho Biotech and Alza International, Inc. They
also contacted the original physicians and found follow-up data on all but
10% of the patients, he said.
A preliminary analysis did not turn up any significant differences in
outcome. Overall progression-free survival was 21.7 weeks for the pegylated
liposomal doxorubicin cohort vs 22.4 weeks for the paclitaxel cohort. The
overall response rates were 17.8% for pegylated liposomal doxorubicin and
22.4% for paclitaxel. Median overall survival was 45.7 weeks for pegylated
liposomal doxorubicin and 56.1 weeks for paclitaxel.
"The overall survival curves pretty much superimposed," Dr. O’Byrne
said, adding, "Overall toxicity was identical for both arms."