Tumori Journal

To evaluate survival in prostate cancer patients in the Province of Florence where the Tuscany Cancer Registry is active.

The survival of 777 patients with prostate cancer diagnosed in the period 1985-87 was evaluated. The observed and relative survival rates 1, 3 and 5 years after diagnosis were computed. Also the prognostic effect of age, disease extension, tumor grade, histological verification, place of residence and year of diagnosis were evaluated using univariate and multivariate analysis.

The observed survival was 73.4% 1 year, 42.5% 3 years and 29.2% 5 years after diagnosis. The relative survival was respectively 78.7%, 53.0% and 43.0%. Significant independent risks were evident when the disease was extended out of the prostate, for patients older than 80 years, for high grade tumors and for patients without histological verification.

The 5-year relative survival rate in the province of Florence is similar to those from other European Registries and the Latina Registry, but much lower than the one reported by the SEER program in the US. Data on histological verification percentage, availability of information on disease extension, and tumor grade are discussed as indicators of the quality of the diagnostic approach in comparison with other registries.

We evaluated some standardized criteria for classifying incident cases of liver cancer into either primary liver cancer (PLC) or unspecified liver cancer (ULC) on the basis of the diagnostic examinations performed and their results.

A pilot hospital-based study (98 cases) was carried out in Verona, northern Italy, with the main aim of assessing the feasibility of the method. The same procedures were subsequently applied in a population-based study (349 cases) in Brescia, northern Italy.

Diagnosis was made on histologic data in 38.7% and 41.8% of the hospital based and population-based studies, respectively, with a wide variation among different hospitals. The percentage of cases classified as PLC was 78.6% in the hospital-based study and 78.8% in the population-based study. No differences in the proportion of cases attributed to PLC were found according to patients’ age and sex or hospital of admission. The repeatibility of the procedure was assessed by a cross-panel review of 198 cases, and concordance was found in 91.9% of them.

An operational method for case definition of PLC based on the results of the diagnostic examinations currently performed and some suggestions for cancer registration are proposed.

The study assessed the role and potential benefit of rhG-CSF in reducing the frequency, duration and severity of neutropenia following cytotoxic chemotherapy according to the E-SHAP protocol and, at the same time in improving the response rate.

Twenty patients with resistant/relapsed intermediate or high-grade non-Hodgkin's lymphoma were treated with the E-SHAP regimen (etoposide + methyl prednisolone + high dose cytosine arabinoside and cisplatin), and in 15 of them, we administered rhG-CSF between chemotherapeutic courses.

The 15 patients who received G-CSF after E-SHAP were neutropenic for a short time and experienced no febrile episodes or infective complications. In contrast, in the group (5 patients) who did not receive G-CSF, the WBC nadir was lower and the number of days with a neutrophil count below 1.0 × 10⁹/L was longer, with a greater risk of inferctious complications. Of the 15 patients, only one had a delay in chemotherapy administration, and the RDI was 95% in the 65% of patients who received G-CSF. Of 5 patients treated with chemotherapy alone, 4 had a delay and the RDI was over 95% in only one patient. We obtained a good overall response rate (70%) in the group who received G-CSF. In the historical group of 5 non-Hodgkin lymphoma patients, we observed only 1 partial response and 4 had progression of disease.

Administration of G-CSF is associated with an acceleration of neutrophil recovery, indicating its potential to reduce the risk of infection. The use of G-CSF permitted us to administer intensive chemotherapy without delay and according to standard dosage, with an improved response rate.

About 50% of recurrence after resection of hepatic metastases from colorectal cancer remain confined to the liver. Adjuvant locoregional treatments could reduce the failure rate, but these treatments have been scantily investigated. Experimental models have shown that both intra-arterial chemotherapy (IAC) and intraportal chemotherapy (IPC) in adjuvant setting were able to reduce metastatic growth, but IPC should be initiated in the immediate postoperative period.

To evaluate the feasibility of immediate postoperative IPC of fluorouracil (5-FU) plus folinic acid (FA) in a consecutive series of patients undergoing hepatic resection for metastatic colorectal cancer.

Forty-three consecutive patients underwent hepatic resection. The first 25 (Control Group = CG) received only surgery; the latter 18 (Treated Group = TG) were candidate to postoperative IPC of 5-FU 750 mg/m² plus FA 20 mg/m²/day continuous infusion for 8 days. One patient was not treated owing to bleeding, thus only 17 received the treatment.

Postoperative morbidity was 14%, equally distributed in both groups. Biochemical hepatic parameters of TG were not statistically different from those of CG. Five patients (29%) developed systemic toxicity: one hematologic grade 4; 3 mucositis grade 3 and one allergic erythema. Three of these patients had been treated by systemic chemotherapy less than one year before.

IPC of 5-FU plus FA in the immediate postoperative period has not yet been tested. The schedule we have investigated neither affected the postoperative outcome, nor influenced hepatic function and regeneration. Systemic toxicity was evident and severe mainly in patients already pretreated by systemic chemotherapy. In these patients, however, toxicity did not affect further outcome. This study confirms the feasibility of immediate intraportal chemotherapy after hepatic resection.

A Phase I study of repetitive courses of chemotherapy (carmustine, cis-platinum, dacarbazine) and immunotherapy (continuous intravenous infusion recombinant interleukin-2 (rIL-2) and subcutaneous (sc) alpha-interferon 2b) plus tamoxifen was performed in order to establish a more efficaciuous way to sequence this kind of treatment for advanced malignant melanoma.

Patients who had measurable metastatic melanoma, a Karnofsky performance status ≥ 80, and no clinically significant hematologic or cardiac disfunction were considered eligible. Treatment consisted of BCNU, 150 mg/m² i.v. day 1 in alternating cycles; DTIC, 220 mg/m² i.v. days 1, 2 and 3; CDDP, 25 mg/m² i.v. days 1, 2 and 3; tamoxifen 10 mg twice/day per os continuously; rIL-2, 18 × 10⁶ IU/m²/day continuous i.v. infusion days 5-8 (96 h) and days 19-22 (96 h); alpha-interferon (IFN) s.c. 3 × 10⁶ U day 12, 6 × 10⁶ U day 14, 9 × 10⁶ U days 16, 19, 21, 23, 26, and 28 (from cycle 2, 9 × 10⁶ U days 2, 5, 7, 9, 12, 14, 16, 19, 21, 23, 26, and 28). Two consecutive cycles were planned until response evaluation.

Three patients were treated according with the protocol; none of them was able to respect the planned dose-intensity schedule. The given dose intensity/planned dose intensity ratios were as follows: DTIC, 0.74 (range, 0.70-0.80); CDDP, 0.77 (0.72-0.80); BCNU, 0.77 (0.72-0.80); rIL-2, 0.65 (0.36-0.80); alpha-IFN, 0.01 (0-0.03); tamoxifen, 1.0. Systemic side effects of rIL-2 and myelotoxicity were the main reasons for treatment delay and/or dose-reduction, and for the long period of hospital care.

We conclude that the treatment schedule is not feasible. However, since we believe that combined chemo-immunotherapy is a potentially active treatment in metastatic malignant melanoma, we have modified it in order to make it more feasible and consequently efficacious.

In vitro and in vivo studies have shown that lonidamine potentiates the cytotoxic effect of anthracyclines in simultaneous and sequential combination. On the basis of such evidence, we evaluated the activity and toxicity of a combination of epirubicin plus lonidamine in advanced breast cancer.

Between January 1991 and November 1993, 33 patients with advanced breast cancer, age <75 years and PS <2, were treated with epirubicin (75 mg/m² i.v. on day 1, every 3 weeks), plus lonidamine (450 mg/day orally from day 1 continuously until disease progression).

Thirty patients were evaluable for response: 4 achieved complete response (13%) and 8 partial response (27%) (total response rate = 40%), 6 (20%) had stabilization of disease, and 12 (40%) progression of disease. The median duration of response was 10 months (range, 4-24+ months). This scheme was tolerated, with a mild additional toxicity related to lonidamine: only WHO grade III myalgia in 1 patient (3%) and epigastralgia in 3 patients (9%).

Although some patients seem to have benefited from the combination at the dose levels of the drug used in the study, the therapeutic advantages of addition of lonidamine remain unclear.

The aim of the study was to assess the activity and toxicity of the vinorelbine-carboplatin combination in advanced adenocarcinoma or large-cell carcinoma of the lung. The new vinca derivative, vinorelbine, shows promising activity when combined with cisplatin, but toxicity of the combination is substantial.

Accordingly, we substituted carboplatin for cisplatin in the combination in order to improve the therapeutic index. From March 1992 to March 1994, 55 untreated patients with undifferentiated unresectable or metastatic adenocarcinoma or large-cell carcinoma of the lung were recruited. The treatment consisted of a course of carboplatin (300 mg/m²) and vinorelbine (25 mg/m²) repeated every 4 weeks. The only grade 3 toxicity observed was 16 cases of grade 3 vomiting and 2 cases of grade 3 stomatitis.

The positive response rate was 40% (partial response, 22 patients). In conclusion, the vinorelbine-carboplatin combination may be regarded as an active, safe regimen for the palliative treatment of advanced adenocarcinoma or large-cell carcinoma of the lung.

Small-cell lung cancer (SCLC) tissue expresses somatostatin receptors and can be visualized by means of the indium-111-labelled somatostatin analogue DTPA-D-Pheoctreotide. The aim of the study was to investigate whether treatment with a cold somatostatin analogue can affect the imaging of somatostatin receptor scintigraphy.

Three patients with SCLC were treated with 200 μg of cold octreotide three times a day subcutaneously for 7 days. Whole body and planar scintigraphy was performed before and after the treatment.

¹¹¹In-DTPA-octreotide uptake was increased in cancer lesions, whereas fixation in normal tissues (liver, spleen, kidneys) decreased.

This is the first demonstration of an enhancement of SCLC imaging following unlabelled somatostatin analogue administration. Similar results have been described by other authors in a limited number of carcinoid tumors.

Immunoglobulin heavy chain gene rearrangement serves as a marker of clonality and cell lineage in B-cell lymphoproliferative disorders. In this study we used the polymerase chain reaction (PCR) to detect clonal rearrangements of the immunoglobulin heavy chain gene in a group of patients with B-cell lymphomas.

DNA was extracted from frozen tissue of 40 B-cell non-Hodgkin's lymphomas and subjected to PCR amplification using primers that recognize conserved sequences of the variable and joining regions of the immunoglobulin heavy chain gene.

Monoclonal rearrangements were detected in 23 of 40 malignant B-cell lymphomas. No clonal rearrangements were detected in the 10 control cases.

We conclude that this PCR-based technique may provide a simplified and rapid approach for the detection of clonal immunoglobulin heavy chain gene rearrangements in B-cell lymphomas without recourse to Southern blotting, which can be reserved for cases in which PCR is negative.

The increased level of blood glutathione (GSH) is an important biochemical feature in animal epithelial tumor. The aim of this study was to investigate the blood GSH concentrations in well characterized cancer patients and healthy volunteers.

Two different groups of carcinoma cases were used. The first group consisted of 15 blood samples drawn from disseminated gastric adenocarcinoma patients, and the second group comprised 15 samples obtained from localized or locally advanced skin carcinoma cases without lymph node metastasis. GSH and hemoglobin concentrations were measured by using the method of Beutler et al.

The mean blood GSH in patients who had advanced malignant disease was 129.13 ± 7.49 mg/dl and in patients who had localized cancer was 96.24 ± 3.90 mg/dl. These results indicate that the blood GSH level is 31% higher in localized carcinoma cases and 78% higher in metastatic disease than those of controls. Blood GSH concentrations were expressed on the basis of blood volume and also on hemoglobin content. Similar results were calculated with either mode of expression.

By comparing the two groups of patients, we found that higher blood GSH concentration was correlated with metastatic growth.

Although systemic metastases from thyroid cancer are relatively frequent, they rarely affect the nervous system and only exceptionally originate from well-differentiated carcinoma.

The authors describe 6 cases of solitary brain metastases from thyroid carcinoma, well-differentiated in 3 cases and anaplastic in the other 3 cases.

Four patients were females and 2 males (M:F ratio, 1:2); average age was 51 yrs (range 48-56). On average, the interval between diagnosis of the thyroid tumor and appearance of the metastasis was 2.8 years (range 1-12 years) and was shorter in the anaplastic forms (1.2 versus 4.4 years). Average survival was 15 months (range 6-48 months); in particular, average survival was longer in patients with well-differentiated carcinoma (9 vs 21 months) as also in those who did not present other metastatic sites (6 vs 24 months). Death was due to systemic progression of the disease in 4 cases and to brain-relapse in the other 2 cases.

Surgery, radioactive iodine (where uptake is demonstrable), and radiotherapy are the main therapies available for metastases from thyroid carcinoma. However, survival of patients appears to be modified by the type of treatment performed.