Christine E Szarka

Publications (2)4.17 Total impact

• Article: Phase I and pharmacokinetic study of irinotecan in combination with raltitrexed.

  Nancy L Lewis, Richard Scher, James M Gallo, Paul F Engstrom, Christine E Szarka, Samuel Litwin, Andrea L Adams, Deborah Kilpatrick, Diane Brady, Louis M Weiner, Neal J Meropol
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  ABSTRACT: To determine the maximum tolerated dose (MTD) of raltitrexed when given with irinotecan and to evaluate the pharmacokinetics of these two agents when given in combination. Patients with advanced solid tumors received irinotecan intravenously over 90 min on days 1 and 8 of each 21-day cycle, with raltitrexed given intravenously over 15 min after irinotecan either on day 1 (cohorts 1-7) or day 2 (cohorts 8-9). The 39 patients received irinotecan and raltitrexed in cohorts of three to six patients at the following dose levels (mg/m(2)): 100/1.0, 100/1.5, 100/2.0, 100/2.5, 100/3.0, 100/3.5, 125/3.0, 75/3.0, 100/3.0. Pharmacologic monitoring of irinotecan and raltitrexed was carried out during cycle 1. A total of 39 patients received irinotecan and raltitrexed in cohorts of three to six patients at nine dose levels. The MTD with dosing of irinotecan on days 1 and 8 and raltitrexed on day 1 was 100 mg/m(2) and 3.0 mg/m(2), respectively, every 21 days, with dose-limiting toxicities (DLTs) of fatigue, neutropenia and diarrhea. When raltitrexed was administered 24 h after irinotecan, these doses exceeded the MTD. No pharmacologic interactions were observed between these agents, and no correlations between pharmacokinetic parameters and toxicity were noted. Of 26 patients with colorectal cancer, 6 had objective partial responses (23%). Four of these patients had previously received a 5-FU-based regimen, two for metastatic disease. Irinotecan can be safely administered with raltitrexed on a day-1 and day-8 schedule at 100 mg/m(2) and 3.0 mg/m(2), respectively, every 21 days. When raltitrexed was given on day 2, these doses were not tolerated, necessitating a dose reduction of the irinotecan to 75 mg/m(2). This regimen possesses clinical activity in patients with colorectal cancer.
  Cancer Chemotherapy and Pharmacology 11/2002; 50(4):257-65. · 2.83 Impact Factor
• Article: Chemoprevention of cancer

  Christine E. Szarka, Generosa Grana, Paul F. Engstrom
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  ABSTRACT: Chemoprevention is a strategy used to block the development of cancers in human beings. This emerging field has broad potential for influencing cancer incidence rates in defined high-risk groups and the general population. In this review, we define some of the mechanisms of carcinogenesis, describe some of the genetic markers of carcinogenesis, and list possible biomarkers that may serve as surrogate end points in chemoprevention studies. A major component of this review is a description of the agents that are currently under investigation in animal systems or in human trials. They are grouped according to the agents that block or suppress mutation, such as oltipraz, selenium, vitamin C and the flavones, or according to agents that block promotion and proliferation, such as difluoromethylornithine, tamoxifen, nonsteroidal antiinflammatory drugs, and the vitamin A derivatives. We describe the issues that are considered in the design of chemoprevention trials and in the phase I, II, and III components of these trials. The following national trials are discussed: the Breast Cancer Prevention Trial, which uses tamoxifen; the Prostate Cancer Prevention Trial, which uses finasteride; and a Lung Cancer Prevention Trial, which uses 13-cis-retinoic acid. The review ends with some insights about future studies in chemoprevention.
  Current Problems in Cancer · 1.33 Impact Factor