Preliminary clinical data was reported at the XXIII Chemotherapy Foundation Symposium in New York, comparing the efficacy and safety of the combination of Thalidomide ( Thalomid ) and Topotecan ( Hycamtin ) vs. Topotecan being studied in a Phase II clinical study for the treatment of recurrent epithelial ovarian cancer in patients who had received prior treatments.
" Our clinical findings have shown that Thalidomide may slow down the growth of ovarian cancer, which could mean more options for physicians treating ovarian cancer, though further clinical studies are warranted," says Levi Downs, at the University of Minnesota's Medical School and Cancer Center who led this study.
At the Chemotherapy Foundation Symposium, Levi S. Downs Jr, at the University of Minnesota Medical School, Division of Gynecologic Oncology, Minneapolis, reported that patients in the Topotecan plus Thalidomide arm reported an overall response rate of 50% compared to 22% of patients in the Topotecan only arm.
Preliminary analysis of the Topotecan plus Thalidomide arm, 32% of the patients achieved a complete response ( CR ) as compared to 16% of patients achieving a CR in the Topotecan only arm ( p=0.03 ).
Furthermore, the preliminary clinical data suggests that patients in the Topotecan plus Thalidomide arm achieved a median progression free survival ( PFS ) of 6 months compared to 4 months in the Topotecan only arm ( p=0.02 ).
The median overall survival ( OS ) was 19 months for patients in the topotecan plus Thalidomide arm and 15 months in the Topotecan only arm ( p=0.95 ).
This multicenter prospective randomized trial enrolled 75 women between April 2001 and July 2005.
Based on an intent-to-treat analysis, the study evaluated 69 women ( Thalidomide n=28; control n=37 ). Six patients were excluded for never receiving treatment ( Thalidomide n=4; control n=2 ), and patients who were not assessable for response were considered non-responders. Eligible patients had recurrent or persistent epithelial ovarian carcinoma as documented by exam, imaging study or elevated CA-125.
Patients had received 1 or 2 prior Platinum based chemotherapy regimens. Treatment arms were Topotecan 1.25 mg/m2 days 1-5 of a 21-day cycle with or without Thalidomide starting at 200 mg/day and increased as tolerated to 800 mg/day.
Toxicity was graded according to NCI-CTC. The Chi Square test was used to assess differences in response and toxicity. Log rank test was used to compare Kaplan-Meyer survival curves.
Well-characterized prognostic factors, including platinum sensitivity ( 70% of patients ) were equally represented in both arms of the study.
The median Thalidomide dose was 200mg/day, and toxicities were similar between both groups. Adverse events observed were fatigue, constipation, peripheral neuropathy and deep vein thrombosis.
Thalidomide is known to cause nerve damage that may be permanent. Peripheral neuropathy is a common, potentially severe, side effect of treatment with Thalidomide that may be irreversible.
Patients with neoplastic and various inflammatory conditions being treated with Thalidomide in combination with other agents may have an increased incidence of thromboembolic events such as pulmonary embolism, deep vein thrombophlebitis, thrombophlebitis, or thrombosis.
Decreased white blood cell counts, including neutropenia, have been reported in the clinical use of Thalidomide.
In placebo controlled clinical trials of HIV-seropositive patient populations, there have been reports of increased plasma HIV RNA levels associated with Thalidomide therapy.
The most common adverse events observed in clinical use in ENL ( erythema nodosum leprosum ) and HIV-seropositive patient populations are rash, maculo-papular rash, drowsiness/somnolence, peripheral neuropathy, dizziness/orthostatic hypotension, neutropenia, and increased HIV-viral load.
Source: Celgene, 2005