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Background: Pretreated advanced melanoma is a poor prognosis scenario with few, if any, active therapeutic options. The antibody against vascular endothelial growth factor, bevacizumab, has demonstrated increased activity in combination with chemotherapy in many tumors. We intended to evaluate the activity of the combination of weekly paclitaxel and bevacizumab in previously treated metastatic melanoma. Patients and Methods: Patients with previously treated metastatic melanoma received paclitaxel 70 mg/m2 weekly and bevacizumab 10 mg/kg biweekly for 5 consecutive weeks every 6 weeks. Results: Twelve patients were treated. Two patients (16.6%) achieved a partial response and 7 patients (58.3%) stable disease. Responses were seen in soft tissue, lung and brain metastases. Median disease-free and overall survival times were 3.7 and 7.8 months, respectively. Treatment was well tolerated. Main toxicities were grade 3 asymptomatic lymphopenia in 6 patients, grade 3 leucopenia in 2 patients, and grade 3 thrombocytopenia in 1 patient. Conclusions: Our preliminary results suggest that the combination of bevacizumab and weekly paclitaxel is active and safe in patients with metastatic melanoma, warranting further investigation.

Objectives: To evaluate the feasibility and a possible activity range of combination irinotecan (CPT-11), oxaliplatin, and 5-FU in advanced colorectal cancer (ACC). Patients and Methods: A total of 53 patients (51% chemoresistant) were treated. Twenty-eight received monthly intravenous oxaliplatin (120 mg/m2) and CPT-11 (250 mg/m2) on day 1 and a course of 5-FU; these constituted the IRI250 group. Twenty-five received monthly intravenous oxaliplatin (120 mg/m2), CPT-11 (300 mg/m2) on day 1, and a course of 5-FU (IRI300 group). 5-FU administration was carried out as follows. Those with predominant hepatic disease (n = 32) received an intra-arterial infusion of 5-FU (2,500 mg/day on days 1–4); these were the IA-FU group. The remaining 21 patients received intravenous 5-FU (2,600 mg/m2 plus leucovorin 500 mg/m2 on days 1 and 15); these constituted the IV-FUFOL group. Results: Intention-to-treat response rate was 54.7% (4 CR, 7.5%). Twelve patients (22.5%) had stable disease; only 4 (7.5%) progressed. Median progression-free and overall survivals were 10 and 18 months, respectively. One-year progression-free and overall survival rates were 44.3 and 67.4%, respectively. Grade 3–4 toxicities included diarrhea (45.3% of patients), neutropenia (52.8%), mucositis (13.2%), and emesis (11.3%). There were 3 treatment-related deaths (5.7%), all in the IA-FU/IRI300 subgroup. Severe adverse effects requiring chemotherapy dose adjustment were observed in 67.9% of the patients, with odds ratios 9.04-fold higher in the IA-FU/IRI300 group (95% CI: 1.07–76.20) and 0.23-fold lower in the IV-FUFOL/IRI250 group (95% CI: 0.05–0.97). Conclusion: This combination seems to have substantial activity in ACC. Overall toxicity was unacceptable in the IA-FU and IRI300 groups, with diarrhea and cytopenia constituting the dose-limiting side effects. Tolerance and efficacy profiles achieved with IV oxaliplatin (120 mg/m2 day 1), IV CPT-11 (250 mg/m2 day 1) and IV 5-FU 2.6 g/m2 with IV leucovorin (500 mg/m2 days 1 and 15) was favorable and deserves further investigation.

Dose intensity has been related to clinical outcome in several solid tumors. We studied the influence of clinical and cellular parameters on dose intensity received in a series of 53 patients with metastatic breast cancer or advanced ovarian cancer. They received courses of cisplatin 120 mg/m2 plus etoposide 600 mg/m2 alternating every 14 days with ifosfamide 8 g/m2 plus paclitaxel 200–350 mg/m2. Blood stem cell support was administered after every course except for the first one. Patients with excellent mobilization underwent immunomagnetic selection of CD34+ cells. We found a significant inverse correlation between the CD34+ cell dose infused and the delay for the administration of the next cycle. A CD34+ cell dose between 1.5 and 5 × 106/kg per cycle was found to be feasible and was followed by a median delay of 1day (not different from doses above 5 × 106/kg). Three factors independently predicted the actually received dose intensity in a multiple regression model (R2 = 0.4): previous autologous transplantation, eligibility for immunomagnetic selection (excellent response to mobilization) and median CD34+ cell dose received along the treatment.

Polymorphonuclear leukocyte (PMN) adherence to nylon was studied in the umbilical cord blood of 33 full-term, healthy newborns (NBs) during delivery. The results were compared to the adherence of PMN of peripheral blood in 50 healthy adult blood bank donors. PMN adherence in the NBs (56.64 +/- 3.24) was found to be significantly higher (p less than or equal to 0.01) than in the adults (47.03 +/- 2.01). PMN adherence, either in adults or NBs, is not related to leukocytes, platelets or hematocrit values. It was found to be related only to the percentage of total leukocyte adherence. Also using scanning electron microscopy (SEM), the ultrastructure of the adherence process was analyzed. In these studies we observed a higher tendency to adopt fusiform disposition in the PMN of the adult population. These results suggest that NB PMNs are hyperadherent and that they show a cellular rigidity and a resistance to deformation that could be responsible for the chemotactic alterations previously described in neonates.