title: Pegylated liposomal doxorubicin and mitomycin C in combination with infusional 5-fluorouracil and sodium folinic acid in the treatment of advanced gastric cancer: results of a phase II trial.
abstract: Mitomycin C (MMC) in combination with infusional 5-fluorouracil (5-FU) is a well-tolerated active combination therapy for advanced gastric cancer. Pegylated liposomal doxorubicin (Caelyx) has been combined with this regimen in a phase I study exhibiting promising activity in patients with upper gastrointestinal tumors. In the present study, we investigated activity and tolerability of this three-drug regimen in patients with gastric cancer. Patients with advanced or metastatic gastric cancer were recruited to receive weekly infusional 5-FU (2000 mg/m2) mixed with sodium folinic acid (FA; 500 mg/m2) in one pump (days 1, 8, 15, 22, 29, 36). On days 1 and 29, Caelyx (20 mg/m2) was given as a 1-h, and MMC (7 mg/m2) was applied as bolus injection on days 8 and 36. Treatment courses were repeated on day 57. Twenty-seven patients with a median age of 66 years were recruited in a single center; 56% had histologically proven peritoneal carcinomatosis and 26 patients are evaluable for toxicity. Common Toxicity Criteria of the National Cancer Institute grade 3 toxicity was recorded in 34% of the patients (anemia 12%, leukocytopenia 8%, febrile neutropenia 4%, thrombocytopenia 12%, nausea 15%, diarrhea 8% and mucositis 4%). One patient developed hemolytic-uremic syndrome. One complete (5%) and eight partial responses (42%) were observed in 19 patients evaluable for response according to WHO criteria. Seven patients had no change (37%) and three (16%) progressive disease. Six patients with peritoneal carcinomatosis not amenable to WHO response assessment had progression-free intervals between 8 and 21 months. Median survival for all patients was 14.7 months and median time to progression was 8.4 months. We conclude that this new three-drug combination regimen yields a promising overall response rate (47%) in patients with gastric cancer despite the inclusion of a majority of elderly patients at moderate or high risk of death in this trial. Its safety and good tolerability as established in the phase I trial was confirmed.
authors.affiliation: Onkologisches Zentrum, III Medizinische Klinik, Fakultät für Klinische Medizin Mannheim der Universität Heidelberg, Mannheim, Germany. ulrike.gnad@med3.ma.uni-heidelberg.de
authors.forename: Senta Ulrike
authors.initials: SU
authors.lastname: Gnad-Vogt
authors.forename: Ralf-Dieter
authors.initials: RD
authors.lastname: Hofheinz
authors.forename: Susanne
authors.initials: S
authors.lastname: Saussele
authors.forename: Sebastian
authors.initials: S
authors.lastname: Kreil
authors.forename: Andreas
authors.initials: A
authors.lastname: Willer
authors.forename: Frank
authors.initials: F
authors.lastname: Willeke
authors.forename: Lothar
authors.initials: L
authors.lastname: Pilz
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Hehlmann
authors.forename: Andreas
authors.initials: A
authors.lastname: Hochhaus
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D008081:Liposomes; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D016685:Mitomycin / Q000008:administration & dosage; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D008081:Liposomes; D016685:Mitomycin; D004317:Doxorubicin; D002955:Leucovorin; D005472:Fluorouracil