title: Phase I trial of gemcitabine and paclitaxel in advanced solid tumors.
abstract: OBJECTIVE
  Gemcitabine and paclitaxel are chemotherapeutic agents with clinical antitumor activity in a broad range of malignant solid tumors. Because of preclinical synergy, unique mechanisms of action and resistance, and nonoverlapping toxicities, gemcitabine and paclitaxel combinations are attractive for testing in clinical trials. Prior weekly gemcitabine and paclitaxel regimens administered on a 28-day cycle have been limited by cumulative hematological toxicity on day 15, thus reducing the planned gemcitabine dose intensity. We therefore conducted a phase I trial of a 21-day schedule of weekly gemcitabine and paclitaxel to determine the tolerability, maximum tolerated dose (MTD), and preliminary estimates of efficacy of this regimen.
  
  
  METHODS
  Forty-one patients with advanced malignant solid tumors were accrued. Gemcitabine was given at a fixed dose of 1000 mg/m2 while paclitaxel was administered at an initial dose of 60 mg/m2, then escalated by 15 mg/m2 increments over seven dose levels to a prospectively planned maximum dose of 150 mg/m2. Both agents were infused intravenously on days one and eight every 21 days. At least three patients were enrolled per dose level. No intrapatient dose escalation was allowed.
  
  
  RESULTS
  All patients were assessable for toxicity and 31 were assessable for response. The regimen was generally well-tolerated. Dose-limiting thrombocytopenia was observed in one patient at a paclitaxel dose of 135 mg/m2/week (dose level 6). After expansion of this dose level by 14 additional patients, no further dose-limiting toxicities were observed although one patient at dose level seven died of neutropenic sepsis after completing three cycles. There were eight partial responders for an overall response proportion of 26% (95% CI: 11, 41). Twelve patients (39%) had stable disease.
  
  
  CONCLUSIONS
  This 21-day schedule of gemcitabine and paclitaxel is safe, well-tolerated, and active. The recommended phase II dose is gemcitabine 1000 mg/m2 and paclitaxel 150 mg/m2 on days one and eight every 21 days. The antitumor activity observed with this regimen warrants further investigation.
authors.affiliation: Division of Hematology and Oncology, Department of Internal Medicine, University of California, Davis School of Medicine, Sacramento, California, USA.
authors.forename: Nelson
authors.initials: N
authors.lastname: Lim
authors.forename: Primo N
authors.initials: PN
authors.lastname: Lara
authors.forename: Derick H M
authors.initials: DH
authors.lastname: Lau
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Edelman
authors.forename: Michael
authors.initials: M
authors.lastname: Tanaka
authors.forename: Ghassan
authors.initials: G
authors.lastname: al-Jazayrly
authors.forename: Joan
authors.initials: J
authors.lastname: Houston
authors.forename: Ignacio
authors.initials: I
authors.lastname: Lauder
authors.forename: David R
authors.initials: DR
authors.lastname: Gandara
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D005260:Female; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D009503:Neutropenia / Q000139:chemically induced; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D011446:Prospective Studies; D013921:Thrombocytopenia / Q000139:chemically induced; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D017239:Paclitaxel; D000093542:Gemcitabine