Fixed Dose Rate Infusion of Gemcitabine with Oral Doxifluridine and Leucovorin for Advanced Unresectable Pancreatic Cancer: A Phase II Study

Abstract

The standard beneficial chemotherapy proven for patients with advanced pancreatic cancer is a regimen containing gemcitabine. In the pregemcitabine era, 5-fluorouracil (5-FU) was the standard agent. Oral 5-FU can be added to gemcitabine to improve the efficacy of chemotherapy and to provide better patient convenience. The possibility to improve efficacy of gemcitabine by fixed dose rate infusion (FDRI) was proposed in addition to combining it with 5-FU. We tried a new chemotherapy combining FDRI of gemcitabine with doxifluridine and leucovorin. Eligibility criteria were pathologically proven, chemotherapy-naïve, and metastatic or nonoperable advanced pancreatic cancer. Gemcitabine 1,000 mg/m² was infused over 100 min (days 1, 8 and 15). Doxifluridine 200 mg/m² t.i.d. and leucovorin 15 mg b.i.d. were given orally (days 1–21). Chemotherapy was repeated every 28 days until a patient had received 6 cycles or progression was found. Twenty-nine patients were enrolled from October 2002 to December 2004. A total of 78 cycles were given at a mean of 2.7 cycles per patient. Response could be evaluated in 26 patients. Responses were partial remission in 4/26 patients (15.4%), stable disease in 8/26 (30.8%) and progression in 14/26 (53.8%). All patients progressed except for 2 in partial remission and 2 in stable disease. Toxicities could be assessed in 23 patients. Maximal hematological toxicities greater than grade 2 were leucopenia in 3 patients (11.5%), neutropenia in 2 (7.7%), anemia in 2 (7.7%), thrombocytopenia in 1 (3.8%) and febrile neutropenia in 3 (11.5%). Maximal nonhematological grade 3 or 4 toxicities were asthenia in 1 patient (3.8%), anorexia in 1 (3.8%), vomiting in 1 (3.8%), diarrhea in 2 (7.7%), allergic reaction in 1 (3.8%), hand-foot syndrome in 1 (3.8%) and hyperbilirubinemia in 1 (3.8%). All 29 patients were dead on last follow-up. Median progression-free survival was 3.91 months in 26 evaluable patients and median overall survival was 5.59 months in all patients. Combination chemotherapy including FDRI of gemcitabine seems minimally active for patients with advanced, nonoperable pancreatic cancer. Further research to improve effectiveness of chemotherapy for advanced pancreatic cancer is mandatory.

The Glasgow Prognostic Score Is a Good Predictor of Treatment Outcome in Patients with Unresectable Pancreatic Cancer

“…On the other hand, most of the patients who had stage IVb had to discontinue treatment during the first three cycles, hence reassessment of the initial dosage and interval may be necessary during treatment for patients with multiorgan or distant nodal metastases. Several studies combining GEM with other cytotoxic agents (5-FU, TS-1, CDDP, CPT-11 or leucovorin) have been reported recently [14][15][16][17] , but no statistical difference in survival rate and survival time compared to single-agent GEM was observed. Combination treatment of GEM with radiotherapy has also been investigated.…”

Efficacy of Gemcitabine for Locally Advanced Pancreatic Cancer: Comparison with 5-Fluorouracil-Based Chemoradiotherapy

“…However, at least, gemcitabine alone deserves to be considered as an effective option. At present, there have been no phase III studies on the efficacy of the combination of gemcitabine with other drugs except erlotinib [31] , although a number of drugs have shown favorable effect in phase I-II trials [32][33][34][35][36][37][38] . In addition, it is noteworthy that the longest survivals were observed in patients treated with chemotherapy with gemcitabine followed by chemoradiotherapy, or in the reverse order.…”

KNK437 Downregulates Heat Shock Protein 27 of Pancreatic Cancer Cells and Enhances the Cytotoxic Effect of Gemcitabine

“…Gemcitabine (GEM; 2′-deoxy-2′-difluorodeoxycytidine; Gemzar) is a deoxycytidine analogue with structural and metabolic similarities to cytarabine. For many years, the only active agent for pancreatic cancer was GEM, which has very modest activity [3,4]. However, intrinsic or acquired resistance of pancreatic cancer hinders the therapeutic effect of GEM [5].…”