Treatment of advanced pancreatic cancer with epirubicin, 5-fluorouracil and 1-leucovorin: A phase II study

Background: Preclinical data suggest that the levorotatory isomer of leucovorin (I-LV) can augment the cytotoxic effect; of 5-fluorouracil (5-FU) more effectively than racemic LV. A phase II study was initiated to evaluate the effect of a combination of the pure L-isomer of LV and 5-FU along with epirubicin in patients with advanced pancreatic cancer. Patients and methods. Twenty-eight consecutive, previously untreated patients with measurable metastatic adenocarcinoma of the pancreas were enrolled in this study. Treatment consisted of epirubicin 50 mg/m(2) on day 1 and 5-FU 400 mg/ m(2) plus 1-LV 100 mg/m(2) both administered on days 1 to 5. Treatment cycles were repeated every four weeks for a total of six months unless progressive disease was documented earlier. The study endpoints were survival, toxicity, objective response as well as palliative beneficial effects of the regimen in terms of performance status, body weight and pain. Results. Six patients had a partial response (21%; 95% CI, 8% to 44%) and 10 (36%) stable disease (35%), while the remaining 12 patients (43%) progressed during treatment. The median time to treatment failure was 2.9 months (range 1.2-13.7 months), and the median survival time was six months (range 1.8-19 months), with three patients (11%) being alive after one year. Beneficial palliative effects in terms of performance status, body weight and/or pain were seen in 12 of 28 patients (43%): an improvement in performance status was recorded in four patients, pain was attenuated and/or analgetic consumption reduced by greater than or equal to 50% is eight patients, and five patients had weight gain of > 5% of their pretreatment body weight. Treatment-associated side effects were generally mild to moderate. Severe adverse reactions included (asymptomatic) granulocytopenia in five, mucositis and/or diarrhea WHO grade 3 in four patients. Conclusion. Our data suggest that epirubicin plus 5-FU and 1-LV is a tolerable regimen that has some positive effects in the treatment of pancreatic cancer. Since this regimen, however, is unlikely to offer any major therapeutic advantage compared to monochemotherapy or other combination regimens, the search for novel and more effective cytotoxic agents must continue.