Correlation between HPLC-determined lonidamine serum levels and clinical response in patients with advanced ovarian cancer.

Lonidamine is an energolytic derivative of indazolcarboxilic acid which has been demonstrated to enhance cisplatin activity in ovarian cancer cell lines either sensitive or resistant to this drug, thus suggesting the potential reverting activity of the mechanisms of drug resistance. A study was performed on nine patients with advanced ovarian cancer treated with lonidamine (LND) plus cisplatin (CDDP) as salvage therapy after the failure of first-line platinum containing chemotherapy. Serum LND was determined with a high-performance liquid chromatography (HPLC) method. The objective clinical response included one complete and three partial responses (overall response 44%). High LND serum levels were observed in three of four responding patients. The serum LND concentrations for these patients, detected one hour after the first and second dose administrations, were 15.2 +/- 1.1 and 14.6 +/- 1.4 micrograms/ml, respectively. Toxicity was mild to moderate, except for myalgia. The high serum levels of lonidamine detected in three of four responding patients suggests that the syngerism between LND and CDDP observed ovarian cancer cell lines may be confirmed in clinical practice. However, the potential role of LND in enhancing CDDP activity can be definitely established in large randomized trials.

An on-line semi-automated solid-phase extraction procedure for high-performance liquid chromatographic determination of lonidamine in serum.

A semi-automated solid-phase extraction procedure on-line with gradient elution reversed-phase chromatography permits the determination of lonidamine and its metabolite in human serum. The average recovery from serum at the 2.5 micrograms ml-1 level was (92.8 +/- 3.4)%. The limit of quantitation for a 100 microliter sample size was 50 ng ml-1. The within-day (n = 5) and between-day (n = 5) relative standard deviations for lonidamine determination in serum samples spiked at the 2.5 micrograms ml-1 level were 2.7% and 4.5%, respectively.

Cluster headache attacks treated for up to three months with subcutaneous sumatriptan (6 mg). Sumatriptan Cluster Headache Long-term Study Group.

In the first three months of a 24-month open study to assess the safety and efficacy of subcutaneous sumatriptan 6 mg in the long-term acute treatment of cluster headache, 138 patients treated a maximum of two attacks daily each with a single 6 mg injection. A total of 6353 attacks were treated. Adverse events, reported in 28% of sumatriptan-treated attacks, were qualitatively similar to those seen in migraine long-term trials. Their incidence did not increase with frequent use of sumatriptan. There were no clinically significant treatment effects on vital signs, ECG recordings or laboratory parameters. Headache relief (a reduction from very severe, severe or moderate pain to mild or no pain) at 15 min was obtained for a median of 96% of attacks treated. There was no indication of tachyphylaxis, decrease in the speed of response, or increased frequency of attacks with long-term treatment. This study demonstrated that, in long-term use, subcutaneous sumatriptan 6 mg is a well-tolerated and effective acute treatment for cluster headache.

MCA performance in preoperative breast cancer patients.

Mucin-like carcinoma-associated antigen (MCA) is a new tumor associated antigen expressed on breast cancer cells independent of histological type and recognized by a two-site sandwich EIA (Roche) using the Mab b-12 as capture and detection antibody and a MCA cut-off of 11 U/ml. MCA serum levels were determined in 409 breast cancer patients and in 100 pts with benign breast disease histologically confirmed and staged according to UICC. The sensitivity of MCA regarding the stage of disease was elevated only in metastatic patients (89%) and the MCA values of this group were significantly different compared to those of patients with early or locally advanced breast cancer. In the group of benign patients, the specificity was 81%. The correlation between MCA values and number of involved axillary lymph nodes showed significant differences in the O versus 4-10 node subgroup (p < 0.001), in O versus > 10 and in 1-3 versus 4-10 node subgroup (p < 0.05); elevated MCA sensitivity was found in the 4-10 and > 10 subgroups. In our experience, the determination of MCA is not useful for early diagnosis of breast cancer nor does it indicate the extent of lymph node involvement. With regard to the prediction of tumor recurrence in postoperative patients free of disease, MCA levels increased concomitantly with the clinical evidence of relapse. These findings suggest that the MCA assay is highly sensitive only in patients with metastatic breast cancer; therefore one of the most promising test application seems to be for monitoring the clinical course of advanced disease patients.

Mucin-like carcinoma-associated antigen (mca) serum levels in breast-cancer - a critical-appraisal.

MCA serum levels were determined in 196 patients with benign breast disease (BD) and in 371 patients with breast cancer. MCA values were abnormal in 30.6% of the patients with BD. In breast cancer patients, significant increases were only found in metastatic disease (89.1%). MCA levels were not correlated with tumor size; on the contrary, the tumor marker showed a strict relation to axillary lymph node involvement. Moreover, the location of metastases and the number of sites involved seem to increase MCA concentrations. The MCA antigen seems to be a promising tool only for monitoring patients with advanced breast cancer.

The p53 tumor suppressor gene. A preliminary clinical study in breast cancer patients.

p53 was originally considered to be a nuclear oncogene, but several convergent lines of research have indicated that the wild-type gene functions as a tumor suppressor gene negatively regulating the cell cycle. Mutations in the p53 gene have been detected in many tumor types and seem to be the most common genetic alterations in human cancer. In this preliminary study, sera of 92 patients (pts) with breast disease were analyzed for the presence of the mutant p53 protein (mp53) with a selective immunoenzyme assay employing a monoclonal antibody (PAb 240) specific for the majority of mammalian m p53 but not for the wild-type protein. Of the 10 patients with benign breast disease, only two (20%) showed detectable m p53 levels in the serum. In the breast cancer group, sera from 7 of the 30 pts (23%) without lymph node involvement were positive for m p53, as were 7 out of the 45 pts (15%) with metastatic lymph nodes and 1 out of the 7 pts (14%) with disseminated disease. The specificity of m p53 assay evaluated in 20 healthy controls was 100%. These preliminary results showed that serum positivity for m p53 is not related to breast disease extension. Further studies to assess the utility of m p53 as a possible prognosis factor in breast cancer are currently in progress.

Determination of intraperitoneal mitoxantrone in the serum of cancer patients using a high performance liquid chromatograph coupled to an Advanced Automated Sample Processor (AASP).

A study has been carried out on 10 patients with ovarian cancer treated by intraperitoneal mitoxantrone. The serum concentration was determined by high performance liquid chromatography with spectrophotometric detection. The extracted analyte on the cartridge was injected and eluted on-line into the analytical column by the mobile phase. This improved the signal and sample processing rate, without significant loss in analytical performance. Excellent linearity (r greater than 0.9994) was observed for the calibration curve over the range 1-2000 ng/mL, along with a precision within-day and between-day estimated as 1.5% and 5.6%, respectively. Sensitivity was an order of magnitude higher than that of the comparison method. From a clinical point of view, these preliminary results have shown that intraperitoneal administration is more beneficial than intravenous therapy. Low serum levels (1-30 ng/mL) with a maximum at the first or second hour are revealed.

Measurement of the ovarian cancer-associated antigen CA 125 in monitoring tumor burden and response to chemotherapy.

CA 125 serum levels were measured in 74 patients with ovarian carcinoma. Among 31 patients undergoing a second look laparotomy (SL) after chemotherapy pathologic complete response (PCR) was observed in 14 patients, residual disease (RD) less than 2 cm in 7 patients and RD greater than 2 cm in 10 patients. The disease status was compared to the CA 125 serum levels measured just before SL. Thirteen of the 14 patients with PCR had serum CA 125 values less than 35 U/ml (specificity: 93%). On the other hand, only 10 of the 17 patients with RD showed serum levels greater than 35 U/ml (sensitivity: 59%). Moreover, in the 43 patients receiving chemotherapy, CA 125 levels correlated with the course of the disease in 36 (84%). With regard to early detection of recurrence, in 9/14 patients with PCR, whose CA 125 levels were monitored monthly, by 1 to 7 months an increase of the tumor marker preceded clinical evidence of relapse in 9/9 relapses (100%). In conclusion, CA 125 assay can be helpful in the management of ovarian cancer patients, in monitoring the response to chemotherapy, in the early detection of tumor recurrence, and in predicting the SL findings, although the low sensitivity could be a major drawback in patients with RD before SL.

CA 125 in the monitoring of response to chemotherapy of ovarian carcinoma.

CA 125 serum levels were assessed in 23 patients undergoing chemotherapy for advanced epithelial ovarian carcinoma (EOC). Rising, falling and unchanged levels correlated with disease in 21 out of 23 (95%) cases. Ten out of 11 patients who showed objective response to chemotherapy had a decrease in antigen levels. Two out of 3 patients with stable disease had unchanged values. Progression was always associated with rising levels. CA 125 is a reliable marker for monitoring response to chemotherapy in advanced epithelial ovarian carcinoma.

[Control study of bacterial infections in patients with carcinoma of the breast subjected to radical mastectomy]. / Studio controllo delle infezioni batteriche nelle pazienti affette da carcinoma della mammella sottoposte a mastectomia radicale.

Surgical patients have a high risk of infections. In the breast surgery, a "clean" surgery, the infection rate should not be more than 2%. In this work, we have studied 174 women with breast cancer, which did not receive the antibiotic prophylaxis. After surgery the patients were monitored for infective complications. The total incidence of infections was 5.1%: 3.4% of surgical wound infections and 1.7% of nosocomial infections. The preoperative antibiotic therapy should not be used in the "clean" surgery, as the mastectomy, except in the patients with high infective risk. In fact we can prevent the wound infections of breast surgery with adequate control measures about the aseptic procedures of operating suite, the members of the surgical team and the preparation of the patient.

[Modifications of enzymatic pancreatic secretion during exogenous hormonal stimulation]. / "Modificazioni della secrezione enzimatica del pancreas nel corso di una stimolazione ormonale esogena".

The secretion of lipase, chymotrypsin and total protein secretion was measured on the pancreatic juice collected from the cannulated pancreatic duct of four dogs. The results suggest that the lipase and chymotrypsin can be secreted independently of each other.