120 hours simultaneous infusion of cisplatin and fluorouracil in metastatic breast cancer

Thirty-six patients with metastatic breast cancer, 23 with documented progression of the disease after first-line chemotherapy (CAF or CMF) and 13 without prior chemotherapy, were treated with a simultaneous 120-h infusion of cisplatin (CDDP) and 5-fluorouracil (5-FU). Objective response was demonstrated in 19 patients (52.7%), stable disease in 7 patients (19.4%) and progression of the disease in 10 patients (27.7%). Similar response rate was observed according to tumor site (soft tissues, 50%; bone, 52%; lung, 63%; liver, 55%; and pleura and peritoneum, 42%) and previous treatment (previous chemotherapy, 48%; previously untreated, 61%). Median duration of response was 8 months. Toxicity was characterized by stomatitis and myelodepression and required dose adjustments in 30% of patients. CDDP and 5-FU infusion deserve further investigation because it appeared to have substantial activity in this preliminary study in metastatic breast cancer

120 hours simultaneous infusion of cisplatin and fluorouracil in metastatic breast cancer

Thirty-six patients with metastatic breast cancer, 23 with documented progression of the disease after first-line chemotherapy (CAF or CMF) and 13 without prior chemotherapy, were treated with a simultaneous 120-h infusion of cisplatin (CDDP) and 5-fluorouracil (5-FU). Objective response was demonstrated in 19 patients (52.7%), stable disease in 7 patients (19.4%) and progression of the disease in 10 patients (27.7%). Similar response rate was observed according to tumor site (soft tissues, 50%; bone, 52%; lung, 63%; liver, 55%; and pleura and peritoneum, 42%) and previous treatment (previous chemotherapy, 48%; previously untreated, 61%). Median duration of response was 8 months. Toxicity was characterized by stomatitis and myelodepression and required dose adjustments in 30% of patients. CDDP and 5-FU infusion deserve further investigation because it appeared to have substantial activity in this preliminary study in metastatic breast cancer

The effect of debulking surgery after induction chemotherapy on the prognosis in advanced epithelial ovarian cancer. Gynecological Cancer Cooperative Group of the European Organization for Research and Treatment of Cancer

BACKGROUND. Although the value of primary cytoreductive surgery for epithelial ovarian cancer is beyond doubt, the value of debulking surgery after induction chemotherapy has not yet been defined. In this randomized study we investigated the effect on survival of debulking surgery. METHODS. Eligible patients had residual lesions measuring more than 1 cm in diameter after primary surgery. After three cycles of cyclophosphamide and cisplatin, these patients were randomly assigned to undergo either debulking surgery or no surgery, followed by further cycles of cyclophosphamide and cisplatin. The study end points were progression-free and overall survival. At surgery 65 percent of the patients had lesions measuring more than 1 cm. In 45 percent of this group, the lesions were reduced surgically to less than 1 cm. RESULTS. Of the 319 patients who underwent randomization, 278 could be evaluated (140 patients who underwent surgery and 138 patients who did not). Progression-free and overall survival were both significantly longer in the group that underwent surgery (P = 0.01). The difference in median survival was six months. The survival rate at two years was 56 percent for the group that underwent surgery and 46 percent for the group that did not. In the multivariate analysis, debulking surgery was an independent prognostic factor (P = 0.012). Overall, after adjustment for all other prognostic factors, surgery reduced the risk of death by 33 percent (95 percent confidence interval, 10 to 50 percent; P = 0.008). Surgery was not associated with death or severe morbidity. CONCLUSIONS: Debulking surgery significantly lengthened progression-free and overall survival. The risk of death was reduced by one third, after adjustment for a variety of prognostic factors

Immunophenotypical and functional heterogeneity of dendritic cells generated from murine bone marrow cultured with different cytokine combinations: implications for anti-tumoral cell therapy

Dendritic cells (DC) are professional antigen-presenting cells that can be used as immune adjuvant for anti-tumoural therapies. This approach requires the generation of large quantities of DC that are fully characterized on the immunophenotypical and functional levels. In a murine model, we analysed the in vitro effects of granulocyte–macrophage colony-stimulating factor (GM-CSF) alone or combined with interleukin-4 (IL-4) or Flt3 ligand (Flt3-L) on the number, immunophenotype and functions of bone marrow-derived DC. In GM-CSF cultures, we have identified two populations based on their level of expression of major histocompatibility complex (MHC) class II molecules: MHC-IIhi cells, exhibiting the typical morphology and immunophenotype of myeloid DC (CD11c+ 33D1+ DEC-205+ F4/80+), and MHC-IIlo cells, heterogeneous for DC markers (30% CD11c+; 50% 33D1+; DEC-205−; F4/80+). The addition of Flt3-L to GM-CSF induced a twofold increase in MHC-IIhi DC number; besides, the MHC-IIlo cells lost all DC markers. In contrast, after addition of IL-4 to GM-CSF, the two populations displayed a very similar phenotype (CD11c+ 33D1− DEC-205+ F4/80−), differing only in their expression levels of MHC class II and costimulatory molecules, and showed similar stimulatory activity in mixed leucocyte reaction. We next analysed the migration of these cultured cells after fluorescent labelling. Twenty-four hours after injection into the footpads of mice, fluorescent cells were detected in the draining popliteal lymph nodes, with an enhanced migration when cells were cultured with GM-CSF+Flt3-L. Finally, we showed that MHC-IIhi were more efficient than MHC-IIlo cells in an anti-tumoral vaccination protocol. Altogether, our data highlight the importance of characterizing in vitro-generated DC before use in immunotherapy