title: Phase I study of paclitaxel and day 1/day 8 gemcitabine in patients with solid malignancies.
abstract: A phase I study was designed to evaluate the toxicity of escalating doses of gemcitabine along with fixed-dose paclitaxel in patients heavily pretreated with chemotherapy or radiotherapy. All patients had no prior therapy with the study drugs and possessed both adequate performance and end organ function. Eighteen patients were entered in the study. Characteristics included a median age of 66 years (range, 41 to 77) and stage IV disease in all patients; there were six patients with colon cancer, two with bladder cancer, three with non-small-cell lung cancer, two with esophageal cancer, three with pancreatic cancer, and two with cancer of unknown primary. Paclitaxel (150 mg/m2 over 3 hours) was given on day 1 and gemcitabine (800, 900, and 1,000 mg/m2 over 15 minutes) was given in three separate dose-escalating cohorts (1-3) on days 1 and 8. The treatment cycled every 21 days. The dose-limiting toxicity (DLT) proved to be neutropenia. All nonhematologic toxicities were mild and included gastrointestinal (nausea, vomiting, and diarrhea), dermatologic (rash), and neurologic (paresthesias) disturbances along with transient elevations of liver function tests. The combination of gemcitabine and paclitaxel seems to be well tolerated, and the recommended starting dose for a phase II study, in pretreated patients using a day 1/day 8 treatment schedule, should be 900 mg/m2 for gemcitabine (days 1 and 8) along with 150 mg/m2 for paclitaxel (day 1).
authors.affiliation: Division of Oncology-Hematology, University of Louisville, Kentucky, USA.
authors.forename: D R
authors.initials: DR
authors.lastname: Fleming
authors.forename: S D
authors.initials: SD
authors.lastname: Glisson
authors.forename: L
authors.initials: L
authors.lastname: Bhupalam
authors.forename: G D
authors.initials: GD
authors.lastname: Michelson
authors.forename: G H
authors.initials: GH
authors.lastname: Goldsmith
authors.forename: R V
authors.initials: RV
authors.lastname: LaRocca
mesh_terms: D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy; D003110:Colonic Neoplasms / Q000188:drug therapy; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D003967:Diarrhea / Q000139:chemically induced; D004938:Esophageal Neoplasms / Q000188:drug therapy; D005076:Exanthema / Q000139:chemically induced; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D009367:Neoplasm Staging; D009382:Neoplasms, Unknown Primary / Q000188:drug therapy; D009503:Neutropenia / Q000139:chemically induced; D017239:Paclitaxel / Q000008:administration & dosage* / Q000009:adverse effects; D010190:Pancreatic Neoplasms / Q000188:drug therapy; D010292:Paresthesia / Q000139:chemically induced; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy; D014839:Vomiting / Q000139:chemically induced; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D003841:Deoxycytidine; D017239:Paclitaxel; D000093542:Gemcitabine