Treatment of metastatic colorectal carcinoma with a combination of fluorouracil and recombinant interferon alfa-2b: preliminary data of a phase II study.

From March 1990 to January 1991 52 previously untreated patients with metastatic colorectal carcinoma were enrolled in a phase II study with the combination of interferon alfa-2b and fluorouracil (5-FU). 5-FU 750 mg/m2 per day was administered as continuous infusion for 5 days, then weekly in a dose of 750 mg/m2 as IV push injection starting on day 15. Interferon alfa-2b (Intron A, ESSEX Pharma) 9 x 10(6) units was given subcutaneously three times per week. Response to therapy was evaluated after 3 and 6 months. So far, data on response rates and toxicity are available in 32 patients: partial remission, 10 patients (31%); stable disease, nine patients (28%); progressive disease, 12 patients (37%); toxic deaths, two patients (6%). Projected median survival has not been reached after 11 months. In about one third of the patients severe side effects occurred with leukopenia grade 3 and 4, diarrhea, mucositis and septic complications being the clinically most important. We think that this combination is an effective but toxic regimen in advanced colorectal carcinoma. Further studies must reevaluate both the schedule and the doses of the drugs administered.

Phase II trial of 5-fluorouracil and recombinant interferon alfa-2B in metastatic colorectal carcinoma.

Between February 1990 and April 1991, 59 previously untreated patients with progressive and/or symptomatic metastatic colorectal carcinoma were enrolled in a phase II study of 5-fluorouracil (5-FU) and interferon alfa-2b (IFN-alpha). 5-FU 750 mg/m2/day was administered as continuous infusion for 5 days, then weekly in a dose of 750 mg/m2 as intravenous push injection starting on day 15. IFN-alpha 9 MU was given subcutaneously three times a week. Treatment was given for a maximum of 6 months. 55 patients are evaluable for response and 51 for toxicity. 17 patients (31%) achieved a partial remission, 15 (27%) had stable disease and 21 patients (38%) had progressive disease. Median duration of remission was 5 months and median survival for all patients 10 months. Toxicity was important with two treatment-related deaths and severe leukopenia, fever, diarrhoea and mucositis in about one third of the patients. In our opinion, this regimen is effective but rather toxic in metastatic colorectal carcinoma.

[Individualization of chemotherapy through in vitro predictive determination of the cytostatic sensitivity of malignant tumors]. / Individualisierung der Chemotherapie durch prädiktive In-vitro-Bestimmung der Zytostatikasensitivität maligner Tumoren.

An in-vitro test was developed for predicting the efficacy of anti-tumour chemotherapy. Cell cultures were grown from freshly removed tumours and it was then demonstrated by DNA cytophotometry and immuno-cyto-chemistry whether the growing tumour cells corresponded to those of the original tumour cells. Several cytostatic agents were then tested for their efficacy of inhibiting growth at clinically customary dosage. Growing cell cultures were established in 306 of 413 submitted tumours (74%). They responded quite differently to the various drugs that were tried. The clinical course in 94 cases was observed for minimally four and a mean of eight months to obtain an in-vitro to in-vivo correlation of response, with 178 individual correlations. A discrepancy was recorded in 16% of cases, a false-positive in-vitro sensitivity result was 3.6 times more frequently associated with an in vivo resistance than the reverse. Concordance between test results and clinical tumour response occurred in 84%. The monolayer proliferation assay correctly indicated resistance in 93.8%, sensitivity in 72.8%.

[The results of a modified FAMeth chemotherapy protocol in metastatic stomach carcinoma]. / Ergebnisse eines modifizierten FAMeth-Chemotherapieprotokolls beim metastasierten Magenkarzinom.

Fifty patients with locally far progressed or metastasizing gastric carcinoma were treated with 5-fluorouracil, adriamycin and methotrexate using a slight modification of the FAMeth schema. Full remission was achieved in four patients, confirmed at a second-look operation. Partial remission was achieved in 13 patients, two of whom went into full remission after operative removal of residual tumour. Median duration of remission for the six patients in full remission was 21 months, for those in partial remission five months. Median survival of all 50 patients was seven months, of those in full and partial remission 12 months, and those without remission four months. The results indicate that this protocol of combined operation and chemotherapy can further improve the results of treating metastasizing gastric carcinoma.