Phase I study of rubitecan and gemcitabine in patients with advanced malignancies

P. M. Fracasso; J. S. Rader; R. Govindan; T. J. Herzog; M. A. Arquette; A. Denes; D. G. Mutch; J. Picus; B. R. Tan; C. L. Fears; S. A. Goodner; S. L. Sun

doi:10.1093/annonc/mdf342

Phase I study of rubitecan and gemcitabine in patients with advanced malignancies

P. M. Fracasso, J. S. Rader, R. Govindan, T. J. Herzog, M. A. Arquette, A. Denes, D. G. Mutch, J. Picus, B. R. Tan, C. L. Fears, S. A. Goodner, S. L. Sun

Research output: Contribution to journal › Article › peer-review

7 Scopus 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/m²/day administered orally on days 1-5 and 8-12 in combination with gemcitabine Results: The MTD was defined as rubitecan 1 mg/m² administered orally days 1-5 and 8-12, and gemcitabine 1000 mg/m² 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/m² given orally on days 1-5 and 8-12 in combination with gemcitabine 1000 mg/m² as a 30-min intravenous infusion on days 1 and 8 of a 21-day cycle.

Original language	English (US)
Pages (from-to)	1819-1825
Number of pages	7
Journal	Annals of Oncology
Volume	13
Issue number	11
DOIs	https://doi.org/10.1093/annonc/mdf342
State	Published - Nov 1 2002
Externally published	Yes

Keywords

9-Nitrocamptothecin
Gemcitabine
Gemzar®
Orethecin™
Phase I
Rubitecan

ASJC Scopus subject areas

Hematology
Oncology

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10.1093/annonc/mdf342

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title = "Phase I study of rubitecan and gemcitabine in patients with advanced malignancies",

abstract = "Background: Rubitecan (9-nitrocamptothecin, 9-NC, Orathecin{\texttrademark}) 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/m2/day administered orally on days 1-5 and 8-12 in combination with gemcitabine Results: The MTD was defined as rubitecan 1 mg/m2 administered orally days 1-5 and 8-12, and gemcitabine 1000 mg/m2 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/m2 given orally on days 1-5 and 8-12 in combination with gemcitabine 1000 mg/m2 as a 30-min intravenous infusion on days 1 and 8 of a 21-day cycle.",

keywords = "9-Nitrocamptothecin, Gemcitabine, Gemzar{\textregistered}, Orethecin{\texttrademark}, Phase I, Rubitecan",

author = "Fracasso, {P. M.} and Rader, {J. S.} and R. Govindan and Herzog, {T. J.} and Arquette, {M. A.} and A. Denes and Mutch, {D. G.} and J. Picus and Tan, {B. R.} and Fears, {C. L.} and Goodner, {S. A.} and Sun, {S. L.}",

year = "2002",

month = nov,

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doi = "10.1093/annonc/mdf342",

language = "English (US)",

volume = "13",

pages = "1819--1825",

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TY - JOUR

T1 - Phase I study of rubitecan and gemcitabine in patients with advanced malignancies

AU - Fracasso, P. M.

AU - Rader, J. S.

AU - Govindan, R.

AU - Herzog, T. J.

AU - Arquette, M. A.

AU - Denes, A.

AU - Mutch, D. G.

AU - Picus, J.

AU - Tan, B. R.

AU - Fears, C. L.

AU - Goodner, S. A.

AU - Sun, S. L.

PY - 2002/11/1

Y1 - 2002/11/1

N2 - 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/m2/day administered orally on days 1-5 and 8-12 in combination with gemcitabine Results: The MTD was defined as rubitecan 1 mg/m2 administered orally days 1-5 and 8-12, and gemcitabine 1000 mg/m2 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/m2 given orally on days 1-5 and 8-12 in combination with gemcitabine 1000 mg/m2 as a 30-min intravenous infusion on days 1 and 8 of a 21-day cycle.

AB - 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/m2/day administered orally on days 1-5 and 8-12 in combination with gemcitabine Results: The MTD was defined as rubitecan 1 mg/m2 administered orally days 1-5 and 8-12, and gemcitabine 1000 mg/m2 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/m2 given orally on days 1-5 and 8-12 in combination with gemcitabine 1000 mg/m2 as a 30-min intravenous infusion on days 1 and 8 of a 21-day cycle.

KW - 9-Nitrocamptothecin

KW - Gemcitabine

KW - Gemzar®

KW - Orethecin™

KW - Phase I

KW - Rubitecan

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SN - 0923-7534

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JF - Annals of Oncology

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ER -

Phase I study of rubitecan and gemcitabine in patients with advanced malignancies

Abstract

Keywords

ASJC Scopus subject areas

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