BACKGROUND: Preclinical and clinical data suggest that both leucovorin (LV) and interferon (IFN) can augment the cytotoxic effects of 5-fluorouracil (5-FU). Based on the rationale of biochemical double modulation, the current Phase II study was undertaken. METHODS: Thirty-two previously untreated patients with advanced adenocarcinoma of the pancreas were treated with subcutaneous recombinant alpha-2b-IFN at a dose of 10 million units on 3 consecutive days; LV (200 mg) plus 5-FU (20 mg/kg) were administered as intravenous bolus doses on day 3. Treatment courses were repeated as tolerated in 2-to-3-week intervals, depending on the patient's complete blood count. RESULTS: Of 32 evaluable patients, 4 (12.5%) had a partial response (95% confidence limit, 4-30%) of 4, +6, 7.5, and 9 months' duration, and 13 (40.5%) had stable disease. The median duration of survival for all patients from the start of therapy was 5.5 months. The most common toxicities observed were IFN-related fever during the first course (69%), mild leukopenia (53%), and gastrointestinal symptoms (28%). CONCLUSIONS: Although the combination of 5-FU, LV, and recombinant alpha-2b-IFN in patients with advanced pancreatic adenocarcinoma has some activity and generally was well tolerated, the observed response rate and median survival were not superior to 5-FU monotherapy.
BACKGROUND: Preclinical and clinical data suggest that both leucovorin (LV) and interferon (IFN) can augment the cytotoxic effects of 5-fluorouracil (5-FU). Based on the rationale of biochemical double modulation, the current Phase II study was undertaken. METHODS: Thirty-two previously untreated patients with advanced adenocarcinoma of the pancreas were treated with subcutaneous recombinant alpha-2b-IFN at a dose of 10 million units on 3 consecutive days; LV (200 mg) plus 5-FU (20 mg/kg) were administered as intravenous bolus doses on day 3. Treatment courses were repeated as tolerated in 2-to-3-week intervals, depending on the patient's complete blood count. RESULTS: Of 32 evaluable patients, 4 (12.5%) had a partial response (95% confidence limit, 4-30%) of 4, +6, 7.5, and 9 months' duration, and 13 (40.5%) had stable disease. The median duration of survival for all patients from the start of therapy was 5.5 months. The most common toxicities observed were IFN-related fever during the first course (69%), mild leukopenia (53%), and gastrointestinal symptoms (28%). CONCLUSIONS: Although the combination of 5-FU, LV, and recombinant alpha-2b-IFN in patients with advanced pancreatic adenocarcinoma has some activity and generally was well tolerated, the observed response rate and median survival were not superior to 5-FU monotherapy.
Authors: H Bernhard; E Jäger-Arand; G Bernhard; M Heike; O Klein; J F Riemann; K H Meyer zum Büschenfelde; W Dippold; A Knuth Journal: Br J Cancer Date: 1995-01 Impact factor: 7.640