title: Gemcitabine and interferon-alpha 2b in solid tumors: a phase I study in patients with advanced or metastatic non-small cell lung, ovarian, pancreatic or renal cancer.
abstract: We performed a phase I study combining gemcitabine and interferon (IFN)- 2b in patients with advanced solid tumors to determine the maximum tolerated dose (MTD) and recommended doses for phase II trials. Five dose levels of gemcitabine (mg/m )/IFN- (x10 IU) were planned: 500/5, 1000/5, 1000/7, 1000/10 and 1200/10. Gemcitabine was given once weekly and IFN 3 x weekly for 3 consecutive weeks followed by 1 week of rest (28-day cycles). Between February 1997 and June 1999, 21 patients with advanced pancreatic ( =3), ovarian ( =1), renal ( =10) and non-small cell lung cancer (NSCLC; =7) were enrolled. The MTD was reached at gemcitabine 1000 mg/m and IFN- 7 x 10 IU, with two of three patients having dose-limiting toxicity (thrombocytopenia). The predominant hematologic toxicities (grade 3/4) were neutropenia and thrombocytopenia (13 and five patients, respectively). Three patients had moderate neutropenic fever and one had grade 4 AST/ALT; none required hospitalization. Of the 18 evaluable patients, responses included one partial response (NSCLC) and 10 stable diseases (eight renal cancer). We conclude that the recommended phase II study regimen is gemcitabine 1000 mg/m and IFN- 5 x 10 IU, every 28 days. The results, particularly those in metastatic renal carcinoma, are encouraging and worthy of further evaluation in phase II trials.
authors.affiliation: Tumor Biology Center, Albert-Ludwigs-University Freiburg, 79106 Freiburg i Br, Germany. stefanfuxius@gmx.de
authors.forename: Stefan
authors.initials: S
authors.lastname: Fuxius
authors.forename: Klaus
authors.initials: K
authors.lastname: Mross
authors.forename: Kambiz
authors.initials: K
authors.lastname: Mansouri
authors.forename: Clemens
authors.initials: C
authors.lastname: Unger
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007279:Injections, Subcutaneous; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage; D017567:Karnofsky Performance Status; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011994:Recombinant Proteins; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D003841:Deoxycytidine; D000093542:Gemcitabine