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Phase I Escalation of Gemcitabine Combined with Protracted Oral Etoposide in Gynecologic Malignancies – A Gynecologic Oncology Group Study

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Abstract

Objective: Although improvementshave been made in the management ofpatients with advanced ovarian cancer,long-term survivors are still uncommon. Gemcitabine and prolonged oral etoposidehave shown reproducible single-agentactivity in patients withplatinum/paclitaxel-resistant ovariancancer. This, combined with preclinicalsynergism, prompted the GynecologicOncology Group to determine the maximumtolerated dose (MTD) of this combination.

Methods: Eligible patients hadrecurrent epithelial ovarian cancer,primary papillary peritoneal, or fallopiantube carcinoma. All had received priorplatinum/paclitaxel-based chemotherapy andhad adequate hepatic, renal and bone marrowfunction. Oral etoposide was administeredat 50 mg/m2 for ten days, with threeproposed dose levels for gemcitabine ondays 1 and 8: 400, 550 and 700 mg/m2. Cycles were to be repeated every 28 days. Three patients were to enter at each doselevel.

Results: Patients were enrolled onlyto dose level 1 as this dose exceeded MTD. Of six patients initially enrolled, one wasremoved after three days with fever,ascites and decreased albumin believed notto be treatment related. Five patientswere evaluable for toxicity and response. One of the first three patients developeddose limiting toxicity (DLT) manifested asgrade 4 neutropenia. A second DLT(neutropenic fever and thrombocytopeniaassociated with bleeding) occurred amongthe next three patients; therefore, MTD wasreached at dose level 1. Grade 4toxicities included episodes of neutropenia(4) and thrombocytopenia (3). No objectiveresponse was observed.

Conclusions: Oral etoposide andgemcitabine at this dose and schedule wasassociated with substantial toxicity inthis population. Patients who are previously treated withplatinum/paclitaxel-based chemotherapy maybe at particular risk for toxicity.

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Authors and Affiliations

  1. Division of Medical Oncology, University of Southern California/Norrris Comprehensive Cancer Center, Los Angeles, CA, USA

    Agustin A. Garcia

  2. Division of Medical Science, Fox Chase Cancer Center, Rockledge, PA, USA

    Michael A. Bookman

  3. Department of Gynecologic Oncology, Cancer Institute of New Jersey, USA

    Lorna Rodriguez-Rodriguez

  4. UMDNJ, Department of Obstetrics/Gynecology, New Brunswick, NJ, USA

    Lorna Rodriguez-Rodriguez

  5. Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, MO, USA

    David G. Mutch

  6. Department of Obstetrics and Gynecology, Indiana University School of Medicine, Indianapolis, IN, USA

    Katherine Y. Look

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  1. Agustin A. Garcia
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  2. Michael A. Bookman
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  3. Lorna Rodriguez-Rodriguez
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  4. David G. Mutch
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  5. Katherine Y. Look
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Garcia, A.A., Bookman, M.A., Rodriguez-Rodriguez, L. et al. Phase I Escalation of Gemcitabine Combined with Protracted Oral Etoposide in Gynecologic Malignancies – A Gynecologic Oncology Group Study. Invest New Drugs 20, 383–387 (2002). https://doi.org/10.1023/A:1020633300898

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  • DOI: https://doi.org/10.1023/A:1020633300898

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