Salvage Therapy with Mitomycin and Ifosfamide in Patients with Gemcitabine-Resistant Metastatic Pancreatic Cancer: A Phase II Trial

Abstract

Background: At the time of upfront treatment failure, over half of the patients with advanced pancreatic cancer are candidates for further treatment. Methods: Patients with metastatic gemcitabine-resistant pancreatic cancer were treated with mitomycin 8 mg/m² on day 1, ifosfamide 2,500 mg/m² and mesna 3,000 mg/m² on days 1–3 every 28 days until progressive disease. A positive responder was defined as a patient who was progression free at 6 months from trial enrolment. According to the Fleming design, a sample size of 34 patients was estimated assuming p0 = 0.05 and p1 = 0.20. Results: Between May 2006 and December 2007, 21 patients (median age 56 years; median Karnofsky performance score 80) were enrolled. One patient died before receiving any treatment. Eighteen patients interrupted chemotherapy due to progressive disease (n = 15), toxicity (n = 2) or refusal (n = 1). Grade >2 toxicity consisted of neutropenia in 80% of patients, thrombocytopenia and fatigue in 20% and anemia in 10%. Only 1 patient was progression free at 6 months (5%). One patient had a partial response (5%) and 2 patients had stable disease (10%). Median survival was 3.7 months. Conclusion: Based on the poor outcome observed and on the high level of grade 3–4 toxicity, the trial was prematurely stopped and the mitomycin and ifosfamide regimen was considered insufficiently active in gemcitabine-pretreated advanced pancreatic cancer.

5-Fluorouracil/Leucovorin Combined with Irinotecan and Oxaliplatin (FOLFIRINOX) as Second-Line Chemotherapy in Patients with Advanced Pancreatic Cancer Who Have Progressed on Gemcitabine-Based Therapy

“…Several clinical trials have evaluated the safety and efficacy of second-line chemotherapy after a gemcitabine-based regimen [6,7,8,9,10,11,12]. According to the NCCN Clinical Practice Guidelines in Oncology (version 2.2012) [13], the regimen includes capecitabine, 5-fluorouracil (5-FU)/leucovorin/oxaliplatin [9] and capecitabine/oxaliplatin [10] as options.…”

Encapsulated Cells Expressing a Chemotherapeutic Activating Enzyme Allow the Targeting of Subtoxic Chemotherapy and Are Safe and Efficacious: Data from Two Clinical Trials in Pancreatic Cancer

“…The median duration of survival of all patients from the start of ifosfamide therapy was only three months (range, one to more than 26 months) [ 16 ]. A more recent study that employed ifosfamide 2.5 g/m 2 and mesna together with mitomycin C was prematurely stopped because of a median survival of only 3.7 months that was accompanied by high levels of Grade 3–4 toxicity [ 40 ]. Taken together, these studies and our two studies suggest that the encapsulated cells improve median survival, but that benefit is achieved by using 1 gm/m 2 /day ifosfamide without the toxicities experienced by patients receiving 2 g/m 2 /day.…”

Genetic determinants and potential therapeutic targets for pancreatic adenocarcinoma

“…A phase II study by Cereda et al looking at salvage therapy with mitomycin C and ifosfamide (analog of cyclophosphamide) in gemcitabine-resistant metastatic pancreatic cancer was closed prematurely based on poor clinical outcomes with 71% of patients experiencing chemotherapy interruption due to progressive disease and 80% of patients demonstrating grade >2 toxicity. This study concluded that the mitomycin C and ifosfamide regimen was considered insufficiently active in gemcitabine-resistant metastatic pancreatic cancer (Cereda et al, 2011). …”