Phase I dose escalation study with irinotecan, capecitabine, epirubicin, and granulocyte colony-stimulating factor support for patients with solid malignancies

Preclinical studies using sequences of topoisomerase I and II inhibitors suggested synergism; preliminary clinical studies, resulting in enhanced antitumor responses, confirm this in selected malignancies. This study determined the maximum-tolerated dose (MTD), toxicity, and pharmacokinetics of irin...

Full description

Saved in:

Bibliographic Details
Published in:	American journal of clinical oncology Vol. 31; no. 3; pp. 219 - 225
Main Authors:	Becerra, Carlos R, Verma, Udit N, Tran, Hia T, Tavana, Denise, Williams, Noelle S, Frenkel, Eugene P
Format:	Journal Article
Language:	English
Published:	United States 01-06-2008
Subjects:	Adenocarcinoma - drug therapy Adenocarcinoma - enzymology Adenocarcinoma - secondary Administration, Oral Adult Aged Alopecia - chemically induced Antineoplastic Combined Chemotherapy Protocols - administration & dosage Antineoplastic Combined Chemotherapy Protocols - pharmacokinetics Antineoplastic Combined Chemotherapy Protocols - toxicity Area Under Curve Breast Neoplasms - drug therapy Camptothecin - administration & dosage Camptothecin - analogs & derivatives Capecitabine Deoxycytidine - administration & dosage Deoxycytidine - analogs & derivatives DNA Topoisomerases, Type I - blood DNA Topoisomerases, Type II - blood Drug Administration Schedule Drug Resistance, Neoplasm Drug Synergism Epirubicin - administration & dosage Female Fluorouracil - administration & dosage Fluorouracil - analogs & derivatives Gastrointestinal Diseases - chemically induced Gastrointestinal Neoplasms - drug therapy Granulocyte Colony-Stimulating Factor - administration & dosage Hematologic Diseases - chemically induced Humans Infusions, Intravenous Lung Neoplasms - drug therapy Male Maximum Tolerated Dose Middle Aged Topoisomerase II Inhibitors Treatment Outcome
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	Preclinical studies using sequences of topoisomerase I and II inhibitors suggested synergism; preliminary clinical studies, resulting in enhanced antitumor responses, confirm this in selected malignancies. This study determined the maximum-tolerated dose (MTD), toxicity, and pharmacokinetics of irinotecan (CPT-11), capecitabine, and epirubicin in patients with metastatic adenocarcinoma of lung, breast, or gastrointestinal tract. Correlation of topoisomerase IIbeta was also done. Eligibility criteria included the following: documented adenocarcinoma of the lung, breast, or gastrointestinal tract, <3 prior chemotherapy regimens, Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2, age > or =18 years, adequate organ function, and signed informed consent. Irinotecan was administered at 250 mg/m2 intravenously day 1 every 21-day cycle, but was reduced to 180 mg/m2 in cohort 2 due to toxicity. Capecitabine was administered at 750 mg/m2 twice daily days 2 to 14 in cohort 1 but only on days 2 to 7 from cohort 2 due to early neutropenia and to allow for prophylactic granulocyte colony-stimulating factor (GCSF) support. Epirubicin was administered at 40 mg/m2 in cohort 1, but reduced to 30 mg/m2 in cohort 2, then reescalated until the MTD was reached. Toxicity was assessed in 21 patients; response was assessed in 17 patients. The most common grade 3 to 4 toxicities included neutropenia (57.1%) and anemia (28.6%). The MTD of epirubicin was 50 mg/m2. In evaluable patients, there were 2 partial responses (11.8%) and 13 stable disease (76.5%); these correlated well with topoisomerase IIbeta. The recommended doses for phase II studies: irinotecan 180 mg/m2 day 1, epirubicin 50 mg/m2 day 2, and capecitabine 750 mg/m2 twice daily days 2 to 7 of each 21-day cycle. This combination is reasonably active and warrants evaluation in the phase II setting.
ISSN:	0277-3732 1537-453X
DOI:	10.1097/COC.0b013e31815a438f