title: Biomodulation of capecitabine by paclitaxel and carboplatin in advanced solid tumors and adenocarcinoma of unknown primary.
abstract: Paclitaxel and carboplatin upregulate thymidine phosphorylase and thus may provide synergistic antitumor activity in combination with capecitabine (CTX). We, therefore, performed a phase I/II study of CTX. In the phase I study, patients with advanced solid tumors received carboplatin on day 1, paclitaxel on days 1, 8, 15 and capecitabine orally twice a day on days 8-21, every 4 weeks. Phase II patients with advanced adenocarcinoma of unknown primary (ACUP) were treated at the maximal tolerable dose. The phase I study enrolled 29 patients evaluable for dose limiting toxicity. The recommended phase II dose was capecitabine 750 mg/m(2) bid, paclitaxel 60 mg/m(2)/week and carboplatin AUC of 6. There were 9 confirmed responses, 5 partial responses and disease stabilization >3 months in 14 patients. The phase II study was prematurely terminated at 25 patients due to cessation of funding. The objective response rate was 32 % (95 % CI 0.15-0.54), the median progression-free survival 5.5 months (95 % CI 2.8-10.8 months) and the median overall survival 10.8 months (95 % CI 6.0-32.0 months). CTX demonstrated acceptable tolerability and antitumor activity. At the recommended dose level in patients with ACUP, this regimen showed encouraging preliminary activity.
authors.affiliation: Richard Solove Research Institute, The Ohio State University Comprehensive Cancer Center-James Cancer Hospital, 320 W 10th Avenue, Columbus, OH, 43221, USA. sameh.mikhail@osumc.edu.
authors.forename: Sameh
authors.initials: S
authors.lastname: Mikhail
authors.affiliation: Richard Solove Research Institute, The Ohio State University Comprehensive Cancer Center-James Cancer Hospital, 320 W 10th Avenue, Columbus, OH, 43221, USA.
authors.forename: Maryam B
authors.initials: MB
authors.lastname: Lustberg
authors.affiliation: Richard Solove Research Institute, The Ohio State University Comprehensive Cancer Center-James Cancer Hospital, 320 W 10th Avenue, Columbus, OH, 43221, USA.
authors.forename: Amy S
authors.initials: AS
authors.lastname: Ruppert
authors.affiliation: Richard Solove Research Institute, The Ohio State University Comprehensive Cancer Center-James Cancer Hospital, 320 W 10th Avenue, Columbus, OH, 43221, USA.
authors.forename: Amir
authors.initials: A
authors.lastname: Mortazavi
authors.affiliation: Richard Solove Research Institute, The Ohio State University Comprehensive Cancer Center-James Cancer Hospital, 320 W 10th Avenue, Columbus, OH, 43221, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Monk
authors.affiliation: Richard Solove Research Institute, The Ohio State University Comprehensive Cancer Center-James Cancer Hospital, 320 W 10th Avenue, Columbus, OH, 43221, USA.
authors.forename: Barbara
authors.initials: B
authors.lastname: Kleiber
authors.affiliation: Richard Solove Research Institute, The Ohio State University Comprehensive Cancer Center-James Cancer Hospital, 320 W 10th Avenue, Columbus, OH, 43221, USA.
authors.forename: Miguel
authors.initials: M
authors.lastname: Villalona-Calero
authors.affiliation: Richard Solove Research Institute, The Ohio State University Comprehensive Cancer Center-James Cancer Hospital, 320 W 10th Avenue, Columbus, OH, 43221, USA.
authors.forename: Tanios
authors.initials: T
authors.lastname: Bekaii-Saab
mesh_terms: D065767:Activation, Metabolic / Q000187:drug effects; D000230:Adenocarcinoma / Q000188:drug therapy*; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000069287:Capecitabine / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004790:Enzyme Induction / Q000187:drug effects; D004938:Esophageal Neoplasms / Q000188:drug therapy; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D009382:Neoplasms, Unknown Primary / Q000188:drug therapy; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D010190:Pancreatic Neoplasms / Q000188:drug therapy; D011355:Prodrugs / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D013939:Thymidine Phosphorylase / Q000235:genetics / Q000378:metabolism; D016896:Treatment Outcome; D015854:Up-Regulation / Q000187:drug effects; D055815:Young Adult
chemical_list: D011355:Prodrugs; D000069287:Capecitabine; D016190:Carboplatin; C543750:TYMP protein, human; D013939:Thymidine Phosphorylase; D017239:Paclitaxel
keywords: Capecitabine; Carboplatin; Carcinoma of unknown primary; Esophageal; Paclitaxel; Thymidine phosphorylase