Faculty Collaboration Database

Phase I study of rubitecan and gemcitabine in patients with advanced malignancies. Ann Oncol 2002 Nov;13(11):1819-25

Date

11/07/2002

Pubmed ID

12419757

DOI

10.1093/annonc/mdf342

Scopus ID

2-s2.0-0036861917 (requires institutional sign-in at Scopus site)   7 Citations

Abstract

BACKGROUND: Rubitecan (9-nitrocamptothecin, 9-NC, Orathecin) and gemcitabine have single-agent activity in pancreatic and ovarian carcinoma. We conducted a phase I trial to evaluate the maximum tolerated dose (MTD) and toxicities of this combination in advanced malignancies.

PATIENTS AND METHODS: Twenty-one patients with refractory or recurrent malignancies were enrolled in this dose escalation trial. Dose escalation proceeded from a starting level of rubitecan at 0.75 mg/m(2)/day administered orally on days 1-5 and 8-12 in combination with gemcitabine 1000 mg/m(2) administered intravenously on days 1 and 8 of a 21-day cycle.

RESULTS: The MTD was defined as rubitecan 1 mg/m(2) administered orally days 1-5 and 8-12, and gemcitabine 1000 mg/m(2) administered intravenously over 30 min days 1 and 8, given every 21 days. Dose-limiting toxicity was myelosuppression including neutropenia and thrombocytopenia. Other side effects included diarrhea, nausea, vomiting and fatigue. Five patients with stable disease were observed among 18 evaluable patients.

CONCLUSIONS: The recommended phase II dose is rubitecan 1 mg/m(2) given orally on days 1-5 and 8-12 in combination with gemcitabine 1000 mg/m(2) as a 30-min intravenous infusion on days 1 and 8 of a 21-day cycle.

Author List

Fracasso PM, Rader JS, Govindan R, Herzog TJ, Arquette MA, Denes A, Mutch DG, Picus J, Tan BR, Fears CL, Goodner SA, Sun SL

Author

Janet Sue Rader MD Chair, Professor in the Obstetrics and Gynecology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Aged
Antineoplastic Combined Chemotherapy Protocols
Biopsy, Needle
Camptothecin
Deoxycytidine
Dose-Response Relationship, Drug
Drug Administration Schedule
Female
Follow-Up Studies
Humans
Infusions, Intravenous
Lymphatic Metastasis
Male
Maximum Tolerated Dose
Middle Aged
Neoplasm Invasiveness
Neoplasm Staging
Neoplasms
Risk Assessment
Survival Analysis
Treatment Outcome