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.
Resistance to paclitaxel has become a significant clinical dilemma since
the agent is now used as first-line therapy in treating advanced ovarian
"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.