High-Dose Folinic Acid and Fluorouracil With or Without Ifosfamide Is an Inactive Combination in Advanced Pancreatic Cancer

Abstract

The Italian Oncology Group for Clinical Research (GOIRC) randomized 55 naive patients with advanced pancreatic cancer (APC) between intravenous fluorouracil (5FU) 400 mg/m2, days 1-5 and folinic acid (FA) 200 mg/m2, days 1-5 alone, using Machover's schedule, or with FU, FA, and ifosfamide (IFO) 5 g/m2, day 1 and Mesna. In both arms, treatment was repeated every 28 days. Fifty-one patients were evaluable for response. The overall response rate was 6% (3 out of 51), 1 out of 29 (3%) complete response (CR) in the arm with FU plus FA, and 2 out of 22 (9%) partial responses (PR) in the arm with IFO. The duration of response rate was 39, 55, and 74 weeks, respectively. Median survival time was 21 weeks (range, 4-83 weeks) for 5FU/FA and 16 weeks (range, 3-106 weeks) for the FU/FA/IFO arm. Diarrhea, mucositis, and vomiting occurred in the majority of patients. One patient died due to toxicity. The combination of 5FU plus FA failed to demonstrate therapeutic activity in patients with APC and was associated with moderate to severe toxicity that could lower the quality of life of these patients. Ifosfamide did not potentiate the activity of this combination. Neither of these combinations should be considered for treatment of patients with APC.

Perspectives on cancer therapy-induced mucosal injury

“…The incidence of oral and GI mucositis varied significantly among different treatment regimens and modalities (Table 4). 60–398 Most anthracycline‐based regimens were associated with rates of oral mucositis in the 1–10% range, except when regimens included 5‐FU. Included among these are the standard regimens for adjuvant therapy in patients with breast cancer (5‐FU, doxorubicin, and cyclophosphamide; doxorubicin and cyclophosphamide; or 5‐FU, epirubicin, and cyclophosphamide) as well as regimens for patients with non‐Hodgkin lymphomas, including cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP).…”

Adjuvant Therapy for Pancreatic Cancer

“…Among the other drugs tested in advanced pancreatic cancer, mitomycin C is probably the most active. The addition of modulators to 5-FU such as folinic acid, N-phosphonacetyl-L-aspartic acid (PALA), or interferon-␣ have not produced substantial improvements in response rates [32,33], although survival rates with multiple modulators-folinic acid ϩ interferon-␣ and folinic acid or mitomycin C ϩ dipyridamole-have shown some encouraging results [34,35]. A new agent, gemcitabine (a nucleoside analog similar to cytosine arabinoside) has shown a significant survival advantage when compared with 5-FU in a randomized trial.…”

Randomized trials in exocrine pancreatic cancer

“…Natomiast połączenie 5-FU z cisplatyną [77][78][79] oraz 5-FU z cisplatyną i interferonem [80] nie zwiększa przeżycia w porównaniu z samym 5-FU. Podobnie, terapie łączone obejmujące 5-FU i ifosfamid [81], 5-FU i CCNU [82] oraz 5-FU i mitomycynę C [83,84] nie zwiększają przeżycia w porównaniu z 5-FU w monoterapii. Siedem badań o stosunkowo dobrej jakości [85][86][87][88][89][90][91] dowodzi, że terapia FAM (5-FU, doksorubicyna, mitomycyna C) nie przynosi korzyści w zaawansowanym raku trzustki, a wręcz wiąże się ze zwiększoną toksycznością.…”