ASCO--Use of the investigational resistance modulator PSC-833 in combination with paclitaxel(Drug information on 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.
Resistance to paclitaxel has become a significant clinical dilemma since the agent is now used as first-line therapy in treating advanced ovarian cancer.
"This compound designed to overcome multidrug resistance could possibly offer a second chance to patients who once responded to treatment with paclitaxel but then had to stop taking the drug because their disease progressed," 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-refractory advanced ovarian cancer. All patients had to have progressed while on paclitaxel-based therapy or to have relapsed within six months of therapy.
These patients received 198 cycles of oral PSC-833 (5 mg/kg four times a day on days 1 to 3) and paclitaxel (70 mg/m² via three-hour infusion on day 2) every 21 days.
Clinical responses were seen in four patients, and a significant decrease in CA-125 levels was observed in an additional seven patients. Although the overall response rates were modest, Dr. Fields said, the data suggest that paclitaxel resistance may be reversed by PSC-833, even in heavily pretreated patients, and accrual to the trial continues. She also noted that further investigation of PSC-833 in randomized phase III trials in combination 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 Medical Center, 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 trial may contact Dr. Fields at Albert Einstein College of Medicine/Montefiore Medical Center. Please call 718-405-8210 for more information.