ASCO--Use of the investigational resistance modulator PSC-833 in combination with paclitaxel (Taxol) is safe and appears to renew paclitaxel response in some patients with refractory advanced ovarian cancer, Abbie L. Fields, MD, said in an ASCO poster presentation of the preliminary results of the phase II study.
ASCO--Use of the investigational resistance modulator PSC-833 in combinationwith paclitaxel (Taxol) is safe and appears to renew paclitaxel responsein some patients with refractory advanced ovarian cancer, Abbie L. Fields,MD, said in an ASCO poster presentation of the preliminary results of thephase II study.
Resistance to paclitaxel has become a significant clinical dilemma sincethe agent is now used as first-line therapy in treating advanced ovariancancer.
"This compound designed to overcome multidrug resistance couldpossibly offer a second chance to patients who once responded to treatmentwith paclitaxel but then had to stop taking the drug because their diseaseprogressed," Dr. Fields commented.
PSC-833, a cyclosporin D analog developed by Novartis Pharmaceuticals,reverses resistance by inhibiting the activity of the P-glycoprotein pump.
Dr. Fields reported on 52 heavily pretreated patients with known paclitaxel-refractoryadvanced ovarian cancer. All patients had to have progressed while on paclitaxel-basedtherapy or to have relapsed within six months of therapy.
These patients received 198 cycles of oral PSC-833 (5 mg/kg four timesa day on days 1 to 3) and paclitaxel (70 mg/m² via three-hour infusionon day 2) every 21 days.
Clinical responses were seen in four patients, and a significant decreasein CA-125 levels was observed in an additional seven patients. Althoughthe overall response rates were modest, Dr. Fields said, the data suggestthat paclitaxel resistance may be reversed by PSC-833, even in heavilypretreated patients, and accrual to the trial continues. She also notedthat further investigation of PSC-833 in randomized phase III trials incombination with first-line paclitaxel-based therapy may be warranted.
Conducted by NYGOG
The study is being conducted by the New York Gynecologic Oncology Group(NYGOG), consisting of Albert Einstein College of Medicine/Montefiore MedicalCenter, where Dr. Fields is assistant professor of gynecologic oncology;New York University Medical Center; New York Hospital/Cornell; and Mt.Sinai Medical Center.
Referring physicians who wish to enroll eligible patients in the trialmay contact Dr. Fields at Albert Einstein College of Medicine/MontefioreMedical Center. Please call 718-405-8210 for more information.