Patrizia Seminara

Chronic Neutrophilic Leukemia and Myeloma. Report on Long Survival

A case of chronic neutrophilic leukemia associated with multiple myeloma is described. The patient appears to be the longest surviving case reported in the literature. Since myeloma developed several years after leukemia, the possible precancerous role of myeloproliferative syndromes is proposed.

Elevated doses of carmustine and mitomycin C, with lonidamine enhancement and autologous bone marrow transplantation in the treatment of advanced colorectal cancer: Results from a pilot study

10 patients with advanced colorectal cancer were treated with elevated doses of carmustine and mitomycin C. The regimen was potentiated by lonidamine and supported by autologous bone marrow transplantation. The results of this pilot study were encouraging, with a response rate of 50% and a significantly better survival for responders versus non-responders. No appreciable toxicity of the therapy was observed. This aspect, together with the simplicity of the procedure, calls for further investigations to confirm the good therapeutic index of the treatment.

5-Flugrouracil (FU) and mitomycin c (MMC) in the management of colorectal carcinoma. part ii.in vitro activity of the two drugs in short term tumor cultures

Eighty-seven colorectal adenocarcinomas from untreated patients were investigated by short term tumor cultures to testin vitro sensitivity to 5- fluorouracil and mitomycin C. This study reports the preliminary results of a multistep program aimed at the prospective clinical application of the assay. At present this in vitro experience was performed in parallel with a clinical trial carried out with the same drugs. The in vitro activity of the two anticancer agents is in agreement with the response rate reported in monochemotherapy; our data would suggest an increase of responses using the combination of fluorouracil and mitomycin in comparison to single drug therapy. A low cosensitivity rate and a high number of cases sensitive to one drug but resistant to the other, account for the use of this test as screening of active drugs in the individual patient.

The non-producer plasma cell myeloma - Report of a case and review of the literature

SummaryA case of non-producer multiple myeloma (MM) is described and compared with the previous reports. Some recurrent clinical traits seem to characterize this disease. It is interesting that reported cases seem to show a low aggressivity. Some biological problems connected with this form of disease are discussed.

Mitomycin C and Etoposide in Advanced Colorectal Carcinoma

Background: Aim of this study was to evaluate the activity of a combination regimen of chemotherapy containing mitomycin C (MMC) and etoposide (ETO) in advanced colorectal carcinoma. Methods: Fourteen pretreated patients received MMC 2 mg/m2 and ETO 60 mg/m2, days 1–5 every 28 days. The clinical study was interrupted since no clinical response was observed in 14 patients following four courses of chemotherapy. An in vitro study was then performed on HTC-8 cell line. The cytotoxic activity of the MMC/ETO combination was tested by sulforhodamine B assay and the type of drug interaction was assessed using the method of Chou and Talalay. Cell cycle perturbations and apoptosis were evaluated by flow cytometry. Results: While MMC and ETO were singularly active, the simultaneous exposure of cells to both drugs and the sequence MMC→ETO ensued in antagonistic interaction at all levels of killed cell fraction. Conversely, the sequence ETO→MMC produced a synergistic interaction. Conclusions: These results suggest that the activity of the MMC/ETO combination is highly schedule-dependent and that the experimental drug associations should be based on a preclinical rationale before clinical trials are designed.

Cancer-associated hemolytic-uremic syndrome with spontaneous resolution. A case report.

A case of cancer-related hemolytic-uremic syndrome is reported. The patient presented a spontaneous recovery, which is unusual in this clinical picture. Mitomycin C is regarded as responsible for this toxic event in most cases. The case history reported here is discussed in relation to dose and scheduling of mitomycin C, and a safe maximum dosage in suggested.

HYPEREOSINOPHILIC SYNDROME AND PLASMOCYTOMA, REPORT OF A CASE AND REVIEW OF THE LITERATURE

The 4th case of plasma cell neoplasm associated with a hypereosinophilic syndrome is described and compared with the previous reports. Hypereosinophilia in the present patient displayed some borderline traits with eosinophilic leukemia. Myeloproliferative disorders of the eosinophilic line often present as a precancerous state, but sometimes they seem to acquire malignant independence. In our patient the occurrence of a plasmocytoma with a dramatic course leads to suspect an underlying complex genetic aberration.

Activity of Ruboxyl, a Nitroxyl Derivative of Daunorubicin, on Experimental Models of Colorectal Cancer Metastases

We evaluated the activity of ruboxyl (Rbx), a nitroxyl analogue of daunorubicin (Dauno), in experimental models of hepatic metastases from colorectal carcinoma (CRC) and compared it with its parent compound and with 5-fluorouracil (5FU). In mice treated by intraperitoneal injections Rbx and 5FU proved more effective than Dauno: the Index of Inhibition of Metastases in comparison with controls was 43% for Dauno, 70% for 5FU and 84% for Rbx. In BDIX rats implanted with the syngeneic cell line DHD K12/TRb, both Rbx and 5FU, administered as a continuous intravenous infusion for 7 days, reduced the development of liver metastases from a median of 23.8 ± 2.16 for controls to 3.2 ± 1.3 for 5FU and 1.0 ± 1.4 for Rbx (p < 0.0001 versus controls for both treatments): the comparison of Rbx and 5FU showed a trend in favour of this new anthracycline. Median survival was prolonged from 40.6 ± 3.4 days in controls to 56.0 ± 5.8 days with Rbx and 58.0 ± 4.69 days with 5FU. Considering that in a phase I study Rbx showed only minor and manageable toxic side effect, its activity in the clinical treatment of CRC metastases may deserve further attention.

In vitro Models of a Three-Drug Regimen (Epirubicin, Cisplatin and Fluorouracil) for the Treatment of Colorectal Cancer

The activity of epirubicin, cisplatin and 5-fluorouracil (5-FU), as single agents or in combination (ECF), was investigated in three human colon cancer cell lines by two different assays (cell-counting assay and sulforhodamine B assay) in vitro. 5-FU was tested with both short and continuous exposure. Particular interest was focused on the results obtained in the HCT8-FU cell line, a subline with experimentally induced resistance to 5-FU. The positive modulation of both cisplatin and epirubicin cytotoxicity by 5-FU makes the ECF regimen an attractive protocol for combination therapy in colorectal cancer.

Drug sensitivity of different tumor lesions from the same patient evaluated by a short-term assay.

A short-term antimetabolic assay, which considers the interference with [3H]thymidine incorporation as an indicator of drug effect, has been used to comparatively assess the chemosensitivity of different tumor lesions from the same patient. The analysis was performed on primary tumors and their synchronous metastases from 67 patients with breast, ovarian, gastrointestinal and germ cell testicular tumors. A remarkable difference in sensitivity to cytostatic drugs was observed between the two lesions. In contrast, a strong association in chemosensitivity (81.7% agreement rate; p < 0.01) was observed between two synchronous metastases from 17 patients with breast, ovarian, germ cell testicular tumors or malignant melanoma. In addition, the predictive relevance of the antimetabolic assay on clinical response to chemotherapy was analyzed in relation to the type of tumor lesion tested in vitro in a retrospective correlative study on 57 patients with advanced ovarian and germ cell testicular tumors. The objective clinical response was significantly correlated to the in vitro sensitivity of metastases (83.7% agreement rate; p < 0.01), but not to that of the primary tumor.