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The aim was to investigate whether intra-arterial infusion of chemotherapy improves response to treatment in unresectable liver metastases from colorectal cancer. We treated 14 patients (pts) with intra-arterial chemotherapy. Arterial catheters were placed via percutaneous access. Treatment schedule was: 5-FU and mitomycin-C on day 1 every 21 days. Six pts also received from day 3 for 5 days, a continuous intra-arterial 24-hr infusion of interleukin-2 (IL-2). We had only one case of toxicity drug-related > grade 2 (neutropenia). We observed 2 partial response (PR) and 5 stable disease (SD). Median time to disease progression (TTP) and median survival (OS) were, respectively 4 and 15 months.

Adoptive immunotherapy trials with tumor infiltrating lymphocytes (TIL) and interleukin-2 (IL-2) were carried out in the treatment of advanced melanoma with a 34% of overall responses (OR). However, theoretically it should be of greater benefit as adjuvant therapy, especially in high-risk stages (stage III and resected stage IV). In a pilot study, 22 patients (aged 23-72 years) with stage III-IV melanoma who underwent radical metastasectomy were reinfused with TIL cultivated and expanded in vitro with IL-2 from surgically removed metastases. IL-2 (starting dose 12 x 10(6) IU/m2) was co-administered as a continuous infusion according to West's scheme. A total of 8/22 (36.3%) patients were disease-free (DF) at a median follow-up of 5 years. DF survival (DFS) and overall survival (OS) in the remaining 14 patients were 44% and 37% and 52% and 45% at 2 and 3 years, respectively. The CNS was the only site of disease recurrence in 57% of patients who relapsed. DF patients received a higher median dose of IL-2 than those who progressed (total dose 110 x 10(6) vs 86 x 10(6) IU/m2, respectively). The progressive reduction in IL-2 dosage allowed all patients to complete treatment without permanent grade 4 toxicity. The effects of tumor immunosuppression in lymphocytes inside the tumor (TCR z and e chains, p56lck, FAS and FAS-ligand) confirmed that the potential function of TIL, immunodepressed at the time of metastasectomy, was significantly restored after in vitro, culture with IL-2. Adjuvant adoptive immunotherapy with TIL and IL-2 seems to improve DFS and OS, in comparison with literature data. Further studies are required to determine its role in the adjuvant treatment of patients with high-risk melanoma.

Aims: Liver resection improves survival in selected patients with colorectal liver metastases. However, the majority of patients with colorectal liver metastases have an inoperable oncological disease. The aim is to investigate whether intra-arterial infusion of chemotherapy, improves response to treatment and may convert a selected group of patients with irresectable liver metastases into an operable state., Materials and Methods: Thirty-sex patients (pts) with inoperable hepatic metastases from colorectal cancer were treated with intra-arterial chemotherapy, by angiographic technique. All patients underwent a short 5-FU-based locoregional infusion and the 13 non pretreated patients also received systemic therapy. Evaluation of response was made by CT scan., Results: Total cycles administered angiographically: 132 (range, 1-11). There were no complications associated with the angiographic procedure and no cases of > grade 2 toxicity. One heavily pretreated pt experienced moderate cholangitis and superficial gastric erosion. Thirty-one pts were assessable (20 pretreated and 11 not); there was 1 complete response (CR), 3 partial remissions (PR), 2 stabilizations (SD) among non-pretreated pts (6/11; CR + PR + SD = 55%) and 1 PR and 8 SD among pretreated pts (9/20; PR + SD = 45%). The remaining 16 pts progressed. Four pts became eligible for radical hepatic resection (1 refused surgery and 3 patients were operated on). There was no peri-operative deaths. Median survival of these 3 pts was 24, 28 and 39+ months., Conclusions: Our data, even if based on a relatively small case series, appear to confirm effective local disease control in this clinical setting. Regional chemotherapy used singly or in combination with systemic chemotherapy may convert a selected group of patients with irresectable liver metastases to an oncological disease that can benefit from surgical treatment.

Aims and Background: Adoptive immunotherapy with tumor infiltrating lymphocyte (TIL) reinfusion plus continuous interleukin-2 (IL-2) infusion could represent an innovative way of treating immunogenic tumors. This study therefore recruited melanoma, colorectal and renal carcinoma patients whose metastases had been surgically removed., Study Design: The treatment was initially given to 22 patients with advanced disease and more recently to 39 disease-free (DF) patients after radical metastasectomy. The latter group was selected in view of a theoretically better lymphocyte/tumor cell ratio and with the aim to improve disease-free and overall survival (DFS-OS) in very high risk patients. The starting IL-2 dose was 12 MIU/day (West's schedule); doses were modulated on the bases of toxicity parameters. Even though patients received different total amounts of IL-2, all of them completed the treatment., Results: The treatment was offered to 22 advanced-stage cancer patients (12 melanomas, 9 colorectal carcinomas, 1 kidney carcinoma). Few and short stabilizations were observed with a median survival of 12 months (range, 3-29). Subsequently, another 39 patients were treated in an adjuvant setting after radical metastasectomy (18 melanomas, 19 colorectal carcinomas, 2 kidney cancers). Eleven out of 17 DF melanoma patients (64.7%) are still free of disease after a median of 37+ months (range, 5+ - 69+). In the group of DF colorectal cancer patients eight (44.4%) are still DF after a median of 21+ months (range, 7+ - 67+ months). One of the two patients with kidney cancer is still DF after 28+ months. Two patients (1 melanoma and 1 colorectal cancer) had just been treated and were therefore not evaluable. Severe toxicity occurred in three cases but was rapidly resolved. There was a great diversity in IL-2 doses administered; comparison of the total IL-2 dose administered between the patients who are still DF and those who progressed revealed no difference between the two groups of colorectal cancer patients, whereas melanoma patients who progressed received an average IL-2 dose of 6.5 MIU/day versus 15.8 MIU/day in DF patients. No differences were observed in any of the groups between the number of TILs reinfused and clinical response., Conclusions: The study is still ongoing; it has been decided to focus on DF melanoma patients after radical metastasectomy, for whom the data seem to be encouraging. Further endpoints of the study are the role of IL-2 dosage in the adjuvant setting, and the possibility to make correlations between biological parameters and clinical results.

A 37-year-old patient with liver metastases from gastric cancer was treated with a double adoptive immunotherapy regimen comprising tumor-infiltrating lymphocytes plus interleukin-2 and subsequently local-regional lymphokine-activated killer cells plus interleukin-2 because of an extremely high in vitro cytotoxic specific activity on established gastric cancer cell lines. The necrosis verified in the center of the hepatic metastasis would appear to demonstrate treatment efficacy, but no clinical response was seen. In vitro cytotoxicity data alone are insufficient to predict the clinical efficacy of adoptive immunotherapy.

An epidemiological research on gstric cancer mortality rates carried out in the town of Forì is reported. The results are significant as regards the relation between the urban and rural areas, and show a higher risk for gastric cancer in the rural area. Salivary nitrite measurement in 92 farm workers showed particularly high values (over 30 ppm in 4 individuals). Analysis of histological findings in biopsies performed during endoscopy in 46 persons of the group studied showed a great number of CAG and CAG + IM in asymptomatic individuals.

Ovarian carcinoma is the fifth most common cause of death among women in western countries. It is often diagnosed in an advanced stage (FIGO Stage III and IV) and requires effective chemotherapy as first-line treatment. The advent of cis-platin combined with adriamycin and cyclophosphamide has remarkably increased the response rate in advanced disease. The authors report 31 cases of epithelial ovarian neoplasia, without prior chemotherapy, treated with cis-platin, adriamycin and cyclophosphamide (PAC I). Of the 30 evaluable patients, 15 had clinical complete remissions (cCR = 50%), 10 clinical partial remissions (cPR = 33%) and 5 no response (NR = 17%). The total response (cCR + cPR) was equal to 83%. Twelve of the 15 patients in cCR underwent second-look laparotomy; in 8 of these cases, histologic and cytologic confirmation of CR was obtained. PAC I was found to be a highly effective therapeutic regimen with moderate toxicity. The individual toxicity reported was gastroenteric (nausea and vomiting), but transitory. No chronic toxic side-effects from cisplatin or adriamycin were noted. However, more definitive results must be obtained to verify its impact on the prolongation of survival.

Gastric carcinoma has a very poor prognosis, with a survival rate at 5 years of 13%. Various chemotherapy regimens have been used in the advanced stages of the disease. The best results were obtained using the FAM combination. We treated 38 patients with advanced measurable gastric cancer using the FAM combination and obtained 23.67% complete plus partial remission (CR + PR) (32% with more restrictive criteria for eligible patients) and 34% no change. The median length of response was 30 weeks in CR patients (range 20-100) and 26 weeks (range 12-34) in PR patients. Responsive patients (CR + PR) had a median survival of 12.3 months (range 5-22) compared to nearly 4 months (range 2-8) for unresponsive patients.