Pegylated Liposomal Doxorubicin Being Reconsidered in Relapsed Ovarian Cancer

LEICESTER, England—Pegylated 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."

Toxicities Not Similar

Specific toxicities, however, were not similar. Patients in the pegylated liposomal doxorubicin arm had more nausea and vomiting, stomatitis, and plantar-palmar erythrodysesthesia. The paclitaxel patients had more alopecia, myalgia, arthralgia, and paraesthesias.

The second-look investigators concluded that that study confirms efficacy of pegylated liposomal doxorubicin in relapsed ovarian cancer patients and suggests it is equivalent to paclitaxel for this group of patients. "I think Doxil offers an alternative to paclitaxel in relapsed ovarian cancer particularly in patients with musculoskeletal disorders, and those particularly keen to avoid alopecia," Dr. O’Byrne said." The results support the evaluation of Doxil in the first-line treatment of ovarian cancer."

Franco M. Muggia, MD, of New York University School of Medicine agreed. "Does this relate and encourage testing a combination of Doxil with carboplatin in carboplatin-sensitive relapse? Yes, and I think definitely that is the direction that one should take from this," he said. "And the other implicit question [is] should such a combination also be considered in clinical trials evaluating first line treatment? And that is also a definite yes."