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Purpose: Carboplatin, vindesine and 5-fluorouracil/leucovorin are drugs active in the treatment of non-small cell lung cancer (NSCLC) and they can be administered in an outpatient setting. Retinoids, which are widely used agents in chemoprevention, have been reported to exert (in vitro models) growth inhibitory effects of synergistic type with chemotherapy, and differentiating effects on NSCLC cells., Patients and Methods: 28 patients with advanced NSCLC with measurable disease were entered into the trial. Eligibility criteria included performance status < or = 3 and adequate renal and liver function. Patients with brain metastases were not excluded. Treatment was as follows: Carboplatin (CBCDA) 300 mg/m2 day 1, Vindesine (VDS) 3 mg/m2 days 1 and 5, leucovorin (L) 100 mg/m2, 5-fluorouracil (5-FU) 370 mg/m2 for 5 days and 13-cis retinoic acid (R) 1 mg/kg, administered between chemotherapy courses. After 6 courses of chemotherapy responders were maintained with R, until progression., Results: 120 courses of chemotherapy have been delivered (median 4 courses per patient, range 1 to 6). All patients were evaluable for response and toxicity. Objective responses: 2 complete responses (CR) (7%), 9 partial responses (PR) (32%), 9 stable disease (SD) (32%), 8 progressive disease (PD) (29%). (Response rate 39%, 95% CI: 22% to 60%). Median time to progression was 7.7 months (range 3.4-22) and median survival was 9.7 months (range 0.5-27) with 40% of patients alive after one year. Toxicity WHO: hematological grade 3-4 in 46% of patients, grade 2 diarrhea in 21% of patients, ileus in 14% of patients, Neurologic grade 2 in 11% of patients., Conclusions: The addition of RA to CBDCA, VDS, FU, L, R represents an effective treatment in NSCLC, with manageable toxicity.

Purpose: To investigate, in patients with metastatic breast cancer (MBC), a combination of retinoids, beta-interferon (beta-IFN) and tamoxifen (TAM)., Patients and Methods: This trial was conducted from January 1987 to June 1992 in 85 consecutive patients with MBC. All patients had been treated for metastatic disease: 43 patients received chemotherapy, 35 received hormone therapy and 7 received both. Forty-nine patients, with a better prognosis, and a longer disease-free survival (DFS) were treated with beta-IFN 1 x 10(6) IU/m2 subcutaneously three times a week, TAM 10 mg TID, retinyl palmitate (R) 50,000 IU BID. Thirty-six patients with shorter DFS, were first treated with 8 courses of chemotherapy followed, in responders, by beta-IFN, R and TAM., Results: With a median follow-up of 7 years (minimum 4 years) 59% of 85 evaluable patients responded, 20% had stabilization of disease and 21% progressed. Median response duration was 43 months. Median survival was 28 months and 25% of patients were alive after 9 years. Toxicity of biological therapy was moderate., Conclusions: Our data show that beta-IFN, TAM and R combination is effective as salvage therapy in patients with MBC.

Background: Carboplatin (CBDCA), cyclophosphamide (CTX) and etoposide (VP-16) combination chemotherapy is active in many tumors. A phase I-II study was designed in order to verify toxicity, maximum tolerated dose and activity of CBDCA, CTX and VP-16 given with Granulocyte Colony Stimulating Factor (G-CSF) and thymopentin (TP5), without bone marrow support., Materials and Methods: A group of 12 heavily pretreated patients (PTS), 9 breast cancer, 2 small cell lung cancer and 1 gastric cancer, received fourteen courses of the described combination chemotherapy. Previous treatments were as follows: surgery in 10 PTS, radiotherapy in 7 PTS, chemotherapy in all PTS (median of 9 courses per patient). CBDCA, CTX, VP-16 were given over 3 days. CBDCA doses were calculated and expressed with the area under the concentration versus time curve (AUC). The dose range were as follows: CBDCA AUC 5.5-11 (400-800 mg/m2), CTX 1500-2500 mg/m2, VP-16 450-550 mg/m2, G-CSF was given 5 mg/kg/day from day 4 to day 17. TP5 was given, on alternate days, 1 mg/ kg from day 4 to day 30., Results: 6 PTS developed fever > 38 degrees C for a median (M) duration of 4 days. 4 PTS required platelet support (M of 12 units) and 3 PTS red blood cells support (M of 2 units). Maximum tolerated dose was CBDCA AUC of 8, CTX 2000 mg/m2 and VP16500 mg/m2. No treatment related death occurred. Ten patients had responses and two had disease stabilisation. At the present time 5 PTS are alive and median overall survival is 13 months., Conclusions: These data indicate that dose intensified CT with the support of G-CSF and TP5 may be delivered safely and shows activity in heavily pre-treated patients.

Background: Chemotherapy (CT), fundamental for the treatment of metastatic breast cancer (MBC), rarely cures, due to the presence of minimal residual disease (MRD). Based on the synergistic antiproliferative effect of interferon, retinoids and tamoxifen on breast cancer cell lines, we designed a pilot study to test if a combination of beta-interferon (beta-IFN), retinoids and tamoxifen could improve the progression free survival and overall survival in patients (PTS) treated with CT for MBC., Methods: Thirty-six patients, with stage IV carcinoma of the breast, were treated with a combination of Cyclophosfamide, 5-fluorouracil, 4-epidoxorubicin, vincristine and prednisone every 3 weeks for six courses (FECPV), followed by two courses of methotrexate, mitomycin-c and mitoxantrone (MMM). Treatment was continued, in response, with low dose beta-interferon, retynil palmitate and tamoxifen until disease relapse., Results: Among 36 evaluable PTS, 23 achieved a clinical response (64%) (95% c. i. 48 x 80%), 7 had disease stability (19%), and 6 (17%) progressed. Leukopenia occurred in 15 patients, thrombocytopenia in six, and anemia in 11. 16 patients had nausea/vomiting; stomatitis was observed in nine patients and diarrhea in three. Toxicity of maintenance therapy was mild and mainly hepatic. Median response duration was 31 months (range 5-75+). Median overall survival was 32 months (9-83+)., Conclusions: Our study shows that this regimen is feasible and shows activity in MBC with an acceptable toxicity.

Unlabelled: Unresectable primary hepatocellular carcinoma (HC) and liver metastases (LM) of abdominal tumors (AT) in progression after systemic chemotherapy (CT) have a poor prognosis and few therapeutic options. From 12/91 to 10/93 we treated 20 patients (PTS) 11 men and 9 women, with HC (10) and AT (10) with the following PCE: percutaneous placement of intraarterial hepatic catheter, superselective embolization with lipiodol (5 cc), infusion, mixed with lipiodol, of epirubicine 40 mg/m2, 5-fluorouracil 700 mg/m2, mitomycin-C 10 mg/m2 in 30'. After infusion, the arterial tree was embolized with Ivalon until an almost complete slowing of arterial blood-flow, every 5-6 weeks (W). After a median follow-up of 28 W a total of 35 courses had been administered to 20 PTS. Median (M) age was 69 years. M PS was 2. Okuda stage in HC PTS: 1 stage I, 9 stage II. in 10 HC PTS, positive for hepatitis B virus, CT and b-IFN had failed, while 10 AT PTS (5 colorectal, 2 gastric, 1 uterine, 1 larynx, 1 choledochus) had progressed, after, at least, 2 CT regimens, and had only LM. Median time from the diagnosis of LM in AT PTS was 32 W (12-68)., Toxicity: liver enzyme elevation and LDH elevation were 3 times baseline values, 4 PTS had fever for 6 days, 3 PTS had ileus for 3 days. No myelosuppression was observed. M alpha-fetoprotein value decreased from 468 ng/ml, to 56 ng/ml after PCE.(ABSTRACT TRUNCATED AT 250 WORDS)

23 patients, with advanced oral cavity cancer, radically unresectable or relapsing after surgery and/or radiotherapy, were treated with a chemotherapeutic regimen, including 5-Fluorouracil 1000 mg/m2 and cis-platinum 20 mg/m2 for 5 consecutive days. Retinol palmitate was administered at the dose of 15.000 IU b.i.d. in chemotherapy intervals. In complete or partial responders, radiotherapy was planned on primary tumor. Chemotherapy treatment was well tolerated with G3 haematological toxicity in 30% of patients and G2 gastrointestinal toxicity in 20% of patients. Seven patients (31.8%) had a complete response (CR), 7 patients had a partial response (PR) (31.8%), stable disease was observed in 3 patients (SD) (13.7), while 5 patients progressed (PD) (22.7%). Median time to treatment failure was 5.6 months. Median survival, from start of chemotherapy, was 8 months 237 days (range 8 days-4 years). 12 patients received consolidation chemotherapy on the primary disease site. No patient developed a second tumor. A combined approach, in the treatment of oral cavity cancer, may give prolonged responses, with acceptable toxicity, without interfering on the quality of life.

The prognosis of colon cancer after curative resection is mainly related to the onset of metastases, and especially of liver metastases. In order to prevent metastatic recurrences, the value of adjuvant medical therapy is widely admitted. The aim of the present review was to analyse the conclusions of the main recent randomized trials assessing the comparative value of different adjuvant protocols. The results obtained using either classic systemic infusion or intraportal infusion, which is mainly used with the intent of preventing liver metastases, are reported. At term of this review, we conclude that: adjuvant chemotherapy using combined drugs (5-Fluorouracil + Methyl CCNU, 5-Fluorouracil + Oncovin) did not prove to be more active than 5-FU alone. the beneficial action of a combined 5-FU + Levamisole regimen has been clearly demonstrated for patients with a Dukes C tumor. intraportal adjuvant therapy has been shown to be effective for patients with Dukes B tumors in only one limited trial but this remains to be confirmed. On the basis of the present data, new adjuvant programs using combined chemotherapeutic and immunotherapeutic compounds, and combined systemic and regional infusion, can be envisaged.