title: Pilot study of enhancement of cisplatin activity by high dose cytarabine in advanced gastric and colorectal (G3/G4) cancer.
abstract: The response rate of advanced gastric cancer to cisplatin monotherapy averages 20% and in colorectal cancer no activity of cisplatin monotherapy has been detected in initial studies. Cytarabine is ineffective in gastric cancer and displays borderline activity in colorectal cancer. In vitro studies on cell lines from human digestive cancers have demonstrated a dose and timing dependent enhancing effect of cytarabine on cisplatin antitumor activity. The aim of the present study was to investigate whether this enhancing activity can also be demonstrated in vivo. We have treated 37 patients with advanced gastrointestinal cancer (21 gastric and 16 colorectal), poorly differentiated G3-G4. The treatment included-Day 1: cytarabine 500 mg/m2 0 h and 12 h, cisplatin 15 mg/m2 6 h and 18 h. Day 2-4:cisplatin 30 mg/m2. Cycles were repeated every 4 weeks. Thirty four patients were evaluable for objective response. The overall response rate was 16.7% (CR 2/18, PR 1/18, SD 5/18, PD 10/18) for patients with gastric cancer and 25% (CR 1/16, PR 3/16, SD 7/16, PD 5/16) for patients with colorectal cancer. Grade 4 anemia (WHO criteria) occurred in 1/37 and thrombocytopenia in 1/37 patients. These patients had previous adjuvant chemotherapy. Vomiting grade 3 occurred in 4/37 and hepatotoxicity grade 3 in 1/37 patients. There were no toxic deaths. Our study did not demonstrate any enhancement of cisplatin activity by high dose cytarabine in advanced gastric cancer. There appears to be an enhancing activity on colorectal cancer although true synergism can not be ruled out since cytarabine has a borderline activity in this type of human cancer.
authors.affiliation: Institute of Oncology and Radiology of Serbia, Belgrade, Yugoslavia.
authors.forename: I
authors.initials: I
authors.lastname: Popov
authors.forename: S
authors.initials: S
authors.lastname: Jelić
authors.forename: S
authors.initials: S
authors.lastname: Radulović
authors.forename: Z
authors.initials: Z
authors.lastname: Tomasević
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002454:Cell Differentiation / Q000502:physiology; D002945:Cisplatin / Q000008:administration & dosage; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003561:Cytarabine / Q000008:administration & dosage; D004357:Drug Synergism; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology
chemical_list: D003561:Cytarabine; D002945:Cisplatin