Many phase II studies have reported improved response rates with severe toxicity, doxorubicin (Adriamycin, Pharmacia), and cisplatin in advanced. In an attempt to obtain a better regimen with high efficacy and less toxicity, a combination regimen of etoposide, doxorubicin, and carboplatin (EAC) had been developed and evaluated in this phase II study. Forty-six patients with advanced gastric cancer were enrolled in the study. The treatment consisted of doxoru-bicin 20 mg/m2 IV on days one and seven, etoposide 70 mg/m2 IV on days four, five, and six, and carboplatin 200 mg/m2 IV on days two and eight. Therapy was repeated every four weeks. Patients with stable disease or who responded received an additional two to six cycles of therapy.

Among 45 patients evaluated for response and toxicity, there was a 49% objective response rate, including 7% complete remission and 42% partial response. There was 11% stable disease and 27% progressive disease. Among 11 patients with lymph node metastasis only after a curative gastrectomy, there was an 82% objective response rate, with 27% having complete remission and 55% having partial response.

The median follow-up was 16 months; the median survival duration of all 45 patients was 11 months. The median time to progression was five months. The main toxicity was myelosup-pression, with a high incidence of 82% leukopenia—but only 9% of grades 3 to 4. Gastrointestinal toxicity was mild, with a low incidence of 42% nausea and vomiting and only 2% of grades 3 to 4. There were no chemotherapy-related deaths. With mild and tolerable toxicity, the EAC regimen has active anti-tumor activity in advanced gastric cancer, which might have a positive influence on long-term survival time. It has a high efficacy, especially in patients with lymph node metastasis only after a curative gastrectomy. This regimen deserves further clinical studies for testing activity and toxicity in patients with advanced gastric cancer.

REFRACTORY LEUKEMIA

A study was carried out to investigate the activity of a novel dioxolane L-nucleoside analog, troxacitabine (L-(-)-OddC, BCH-4556), in patients with refractory leukemia. Troxacitibine is a novel nucleoside analog developed by BioChem Pharma. Troxacitabine (BCH-4556) is the first nucleoside with the unnatural f -L-configuration shown to have anticancer activity. Unlike cyto-sine arabinoside (AraC), this cytosine analog is active against both solid and lymphoid tumors in vivo. Although troxacitabine shares a common metabolic pathway for activation with AraC and gemcitabine, it is unlike those two compounds in that it is not converted to an inactive compound by cytidine deaminase. It might therefore be effective in malignant disease in which deamination is a major mechanism of resistance. In addition, troxacitabine is active in cell lines refractory to gemcitabine because of impaired transport, and it is a potent inhibitor and chain terminator of human cellular DNA polymerases. Troxac-itabine has demonstrated substantial preclinical activity against human renal cancer cell lines grown in nude mice. Responses were previously observed in patients with kidney cancer when administered every three weeks.

In the present study, participants were patients with refractory or relapsed acute myeloid (AML) or lymphocytic (ALL) leukemia, myelodysplastic syndromes (MDS), or chronic myel-ogenous leukemia in blastic phase (CML-BP). Troxacitabine was provided as an intravenous infusion for more than 30 minutes daily for five days at a dose of 8 mg/m2/day (40 mg/m2 per course). Courses were given every three to four weeks according to antileukemic efficacy. buy antibiotics canada

Forty-two patients (AML, 18 patients; MDS, one patient; ALL, six patients; CML-BP, 17 patients) were treated. Median age was 51 years (range= 23-80 years); 22 patients were male. Stomatitis was the most significant adverse event, with three patients (7%) and two patients (5%), respectively, experiencing grade 3 or 4 toxicity. Ten patients (24%) had grade 3 hand-foot syndrome, and two patients (5%) had grade 3 skin rash. One patient (2%) had grade 3 fatigue and anorexia. Marrow hypoplasia occurred between days 14 and 28 in 12 (75%) of 16 assessable patients with AML. Two complete remissions and one partial remission (18%) were observed in 16 assessable patients with AML. None of six patients with ALL responded. Six (37%) of 16 assessable patients with CML-BP experienced a return to chronic-phase disease. The results of the study showed that troxacitabine had significant antileukemic activity in patients with AML and CML-BP.