Cetuximab in squamous cell head and neck carcinomas.

The epidermal growth factor receptor (EGFR) antagonist, cetuximab, has recently been shown to enhance the effects of radiotherapy, and reports to date indicate that this effect occurs without any change in the pattern and severity of toxicity usually associated with head and neck radiation and/or chemotherapy (CT) administration. Moreover, several studies have reported that the expression of EGFR is strongly linked to poor outcome in patients undergoing therapy. Therefore, the presence of the EGFR in almost all cases of head and neck carcinoma offers a new therapeutic opportunity to most patients. In this paper, we report a review of the major studies dealing with the use of cetuximab in advanced head and neck cancer.

Hepatic intra-arterial chemotherapy (HIAC) of high dose mitomycin and epirubicin combined with caval chemofiltration versus prolonged low doses in liver metastases from colorectal cancer: a prospective randomized clinical study.

A multicenter randomized study comparing high dose of mitomycin and epirubicin given as hepatic intra-arterial chemotherapy (HIAC) combined with caval chemofiltration (CF) versus low doses of the same drugs in unresectable liver metastases from colorectal cancer showed a significant improvement in the survival rate of the 20 patients treated with high dose compared to the 22 patients treated with low doses with a 1 year survival of 69% vs 39%. The median survival was 17 vs 11 months and the responses were 65% vs 33%. Toxicity was colangitis in 50% of patients considered. The extrahepatic progression was similar in the two groups (7/20 vs 8/22).

Efficacy of the association of folinic acid and 5-fluorouracil alone versus folinic acid and 5-fluorouracil plus 4-epidoxorubicin in the treatment of advanced gastric carcinoma.

A total of 71 patients with advanced gastric carcinoma were randomized to receive either folinic acid + fluorouracil (arm A) or the same combination with the addition of 4-epidoxorubicin (arm B). Of the 62 evaluable patients (31 in both arms), six patients achieved a CR (10%) and 16 a PR (25.5%) with an overall response rate of 35.5% (29% in arm A and 42% in arm B; p = .28). Median duration of response was 6 and 7 months for arm A and B, respectively (p = .6). Responder patients showed a significantly better median survival duration than nonresponders (p = .01); in arm B the median survival duration was 16 months for responder patients in contrast to 7 months for nonresponders (p = .004). Toxicity was mild without significant differences between the two groups. There was one death due to hematological toxicity (arm A). The EPI-FA-FU combination appears effective and well tolerated with the additional advantage of being able to be administered in the outpatient clinic.

Biochemical modulation of fluorouracil with high dose methotrexate or folinic acid in advanced colorectal cancer patients. Gruppo Oncologico dell' Italia Meridionale (GOIM).

To compare the efficacy of two biochemical modulations of 5-Fluorouracil in advanced colorectal cancer, 104 patients were randomized to receive high dose methotrexate followed by 5-Fluorouracil and leucovorin rescue on day 1 (Arm A) or folinic acid and 5-Fluorouracil on day 1 to 5 (Arm B). Both treatments were repeated every 3 weeks. In the 92 evaluable patients, objective responses were observed in 34% in Arm A and 31% in Arm B, with a median duration of 7.5 and 8.5 months, respectively. Median overall survival was similar in both groups (12 versus 13 months, respectively). A statistically significant difference was found only between responders and non responders of group B (p = 0.004). Toxicity was mild. In conclusion, no difference in therapeutic activity was seen between the two treatments and additional biochemical modulation must be evaluated.

Sequential treatment with high-dose methotrexate and fluorouracil in advanced colorectal cancer. Experience of the Southern Italian Oncology Group (GOIM).

A total of 101 patients with advanced colorectal cancer in two consecutive Southern Italian Oncology Groups (GOIM) studies (8501 and 8801--arm A) were treated with a sequential combination of high dose methotrexate (HDMTX) and fluorouracil (FU). Of the 92 eligible patients, 2 achieved complete response (2%) and 27 partial response (30%), with a median duration of 7 months. When classified according to the time interval between administration of the two drugs, retrospective analysis showed significant improvement (p = 0.04) in overall survival in the shorter time interval group (6 hours). The observed toxicities were generally mild and transient. Our data confirm the efficacy of the synergism between the two chemotherapeutic agents, in particular when administered with a 6-hour interval. Further studies are necessary to establish the possibility of enhancing the efficacy of sequential treatment with the modulation of FU with high-dose folinic acid.

Human antithrombin III heterogeneity: a study by isoelectrofocusing and crossed immunoelectrofocusing.

Isoelectrofocusing was carried out in the LKB Multiphor apparatus with pH 4-6.5 carrier ampholines using polyacrylamide gel slabs. Specimens of purified antithrombin III (AT-III), normal plasma and serum were isoelectrofocused. Microheterogeneity was shown by three preparations of purified AT; the protein was separated in at least six bands, three large bands were located in the pH range 4.9-5.2, one intermediate band at pH 4.85, other thinner bands were located in the pH range 4.55-4.80. The microheterogeneity of AT-III was confirmed in purified preparations as well as in plasma and in serum by crossed immunoelectrofocusing. The pattern of purified preparations, normal plasma and serum were very similar; only minor, quantitative differences were noticed. Plasma from a patient with congenital AT-III deficiency showed an abnormal pattern.

Factor VIII complex in myelomatosis and related disorders.

The behaviour of the factor VIII/von Willebrand factor complex (VIII:C, VIIIR:Ag and VIIIR:RCof) was investigated in 23 patients with secretory myeloma, in 2 patients with non-secretory myeloma and in 5 patients with macroglobulinemia. In most patients (21 of 25 patients with plasma cell myeloma and 2 of 5 patients with macroglobulinemia) VIIIR:Ag was increased usually without corresponding increases in VIII:C and VIIIR:RCof. There was no correlation between the VIIIR:Ag levels and paraprotein Ig type or level nor with the presence or the absence of Bence Jones proteins in serum and urine. Furthermore, increased levels of VIIIR:Ag were found in patients with non-secretory myeloma. In general, VIIIR:Ag was higher in patients with extensive bone lesions and there was a significant correlation between cell mass and the VIIIR:Ag level. The crossed-immunoelectrophoresis of plasmas with discrepant VIIIR:Ag and VIIIR:RCof showed variation from the normal pattern.

A comparative study on the effect of dilazep and dipyridamole on some platelet functions.

It was the purpose of this study to examine the effect of 1,4-bis[3-(3,4,5-trimethoxybenzoyl-oxy)propyl]-perhydro-1,4-diazepine (dilazep) on platelet function in vivo, compared with that of dipyridamole. 15 patients were given oral doses of 300 mg dilazep daily, and another 15 patients received oral doses of 450 mg dipyridamole daily. Blood was withdrawn 2 and 4 weeks after the start of treatment, in each case 2 h after administration of the drug. The results were as follows: bleeding time was prolonged in both groups; there was a percentage reduction of circulating platelet aggregates in both groups, but this was statistically significant in the dilazep group only; platelet aggregation was decreased in both groups, several parameters (minimum dose required to induce aggregation, collagen lag phase) were statistically significantly improved in the dilazep group only; platelet malondialdehyde production was unchanged; no changes were demonstrated in platelet shape, fibrinogen concentration, partial thromboplastin time, or prothrombin activity.

Heparin-urokinase treatment in aseptic dural sinus thrombosis.

Five patients affected by aseptic dural sinus thrombosis have been treated with a combination of heparin sodium and urokinase. In all of them, the therapy was followed by complete clinical recovery. Postoperative cerebral angiography showed patency of the involved sinuses in all.

Megathrombocytes, platelet regeneration time and platelet associated IgG in idiopathic thrombocytopenic purpura and in thrombocytopenia associated with chronic liver disease.

Percentage of megathrombocytes, platelet regeneration time (PRT) and platelet-Associated IgG (Pl-A-IgG) were investigated in 12 patients with clinical features consistent with idiopathic thrombocytopenic purpura and in 11 patients with thrombocytopenia associated with chronic liver disease. Bone marrow smears were also examined and megakaryocytes classified into stages I-III according to the current principle. Of 12 patients with idiopathic thrombocytopenic purpura the percentage of megathrombocytes was increased in 9, PRT reduced in 10, and Pl-A-IgG increased in 8 patients. A statistically significant correlation was found between the percentage of megathrombocytes and the level of Pl-A-IgG. A slight correlation was also found between PRT and the percentage of megathrombocytes, while a significant correlation was found between megakaryocytes in stage I and the percentage of megathrombocytes, suggesting that growth of megakaryocytes probably contributes to platelet heterogeneity. In patients with thrombocytopenia and chronic liver disease, the percentage of megathrombocytes was in the normal range. A moderately increased level of Pl-A-IgG was found only in patients with active chronic hepatitis, PRT was reduced only in a few patients, while most of them also showed an increase of Pl-A-IgG.