Phase I/II trial of doxorubicin and fixed dose-rate infusion gemcitabine in advanced soft tissue sarcomas: a GEIS study

Autor: Javier Martín, Joaquin Fra, R Losa, Javier Martinez-Trufero, Antonio Casado, J. Garcia del Muro, Carmen Balana, Antonio Lopez-Pousa, M.I. Sierra, J. M. Buesa, Emilio Esteban, Juan Maurel, Andres Poveda
Rok vydání: 2006
Předmět:
Male
Cancer Research
humanos
gemcitabine triphosphate
Soft Tissue Neoplasms
Pharmacology
Gastroenterology
Deoxycytidine
chemistry.chemical_compound
Bolus (medicine)
Antineoplastic Combined Chemotherapy Protocols
Clinical Studies
Drug Interactions
mediana edad
neoplasias de los tejidos blandos
Aged
80 and over
anciano
Soft tissue sarcoma
protocolos de quimioterapia antineoplásica combinada
gemcitabine
Sarcoma
adulto
Middle Aged
interacciones farmacológicas
Oncology
soft tissue sarcoma
Toxicity
Female
dosis máxima tolerada
medicine.drug
Adult
medicine.medical_specialty
doxorrubicina
Maximum Tolerated Dose
medicine.drug_class
Antimetabolite
doxorubicin
Internal medicine
medicine
Humans
Doxorubicin
Aged
Dose-Response Relationship
Drug
business.industry
medicine.disease
desoxicitidina
Gemcitabine
chemistry
business
Febrile neutropenia
Zdroj: British Journal of Cancer
ISSN: 0007-0920
Popis: The aim of the study was to determine the dose-limiting toxicity and maximum tolerated dose of a first-line combination of doxorubicin and gemcitabine in adult patients with advanced soft tissue sarcomas and to explore its activity and toxicity, and the presence of possible interactions between these agents. Patients with measurable disease were initially treated with doxorubicin 60 mg m(-2) by i.v. bolus on day 1 followed by gemcitabine at 800 mg m(-2) over 80 min on days 1 and 8, every 21 days. Concentrations of gemcitabine and 2',2'-difluorodeoxyuridine in plasma, and gemcitabine triphosphate levels in peripheral blood mononuclear cells were determined during 8 h after the start of gemcitabine infusion. Myelosuppression and stomatitis were limiting toxicities, and the initial dose level was applied for the Phase II trial, where grade 3-4 granulocytopenia occurred in 70% of patients, grade 3 stomatitis in 46% and febrile neutropenia in 20%. Objective activity in 36 patients was 22% (95% CI: 9-35%), and a 50% remission rate was noted in leiomyosarcomas. Administration of doxorubicin preceding gemcitabine significantly reduced the synthesis of gemcitabine triphosphate. Clinical activity, similar to that of single-agent doxorubicin, and the toxicity encountered do not justify further studies with this schedule of administration.
Databáze: OpenAIRE
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