Weekly gemcitabine plus Epirubicin as effective chemotherapy for advanced pancreatic cancer: a multicenter phase II study

Abstract

The current role of chemotherapy in pancreatic carcinoma is limited, and progress in the treatment of this disease represents a significant challenge to medical oncology. The most promising drug under study is gemcitabine, a relatively new antimetabolite that represents an attractive candidate for combination chemotherapy because of its excellent side-effect profile and the absence of overlapping toxicities with other chemotherapeutic agents. Combined administration of gemcitabine and anthracyclines could result in the induction of DNA breaks that are not easily repaired by the cell's machinery, thus enhancing the apoptotic signals triggered by these lesions. Forty-four patients with locally advanced and/or metastatic pancreatic adenocarcinoma were enrolled in this multicenter study. Patients received Epirubicin 20 mg m 72 for 3 weeks followed by 1 week of rest (1 cycle) and gemcitabine 1000 mg m 72 after Epirubicin on the same day. All were assessable for toxicity and response, 11 patients responded to treatment with one complete response and 10 partial responses, for an overall response rate of 25%. Median survival was 10.9 months (range, 2 -26 months). Therapy was well tolerated, with a low incidence of haematologic grade 42 toxicity. A total of 12 of 27 (44.4%) eligible patients attained a clinical benefit response. Our findings suggest that the gemcitabine-epirubicin schedule is active and well tolerated in patients with advanced pancreatic cancer.

A phase I/II multicentric trial of gemcitabine and epirubicin in patients with advanced pancreatic carcinoma

“…Our experience with GEM and EPI clearly demonstrated that this combination is adequately tolerated with moderate toxicities that were qualitatively and quantitatively similar to those reported from other trials (Scheithauer et al, 1999;Neri et al, 2002;Reni et al, 2005).…”

“…Neri et al (2002) reported an overall response rate of 25% and a SD in 41% of their patients. Most patients (77%) in that study were stage IV and two-thirds had a mean KPS between 70 and 80.…”

“…With an additional 35% of patients experiencing SD this combination achieved a favourable disease control in almost 60% of patients. Three other GEM þ EPI studies in pancreatic cancer have been published in manuscript form (Scheithauer et al, 1999;Neri et al, 2002;Reni et al, 2005).…”

“…This compares favourably with the rate of clinical benefit response in the GEM þ EPI studies by Scheithauer et al (1999) (43%) and Neri et al (2002) (44%). However, using the same validated definitions for clinical benefit response, there is almost a doubling of the rate of clinical benefit responders with the combination therapy in comparison with GEM alone (Burris et al, 1997, Neri et al, 2002.…”

Pegylated liposomal doxorubicin in combination with mitomycin C, infusional 5-fluorouracil and sodium folinic acid. A phase-I-study in patients with upper gastrointestinal cancer

“…Ross et al, 2002) or pancreatic cancer (e.g. Neri et al, 2002). They formed part of the FAM (5-FU, doxorubicin, MMC) and FAMtx (5-FU, doxorubicin, methotrexate) regimens, respectively.…”