A Multicenter Phase II Study of Docetaxel in Combination with Gefitinib in Gemcitabine-Pretreated Patients with Advanced/Metastatic Pancreatic Cancer

Abstract

Purpose: To evaluate the efficacy and tolerance of the docetaxel/gefitinib combination as second-line treatment in patients with advanced pancreatic cancer. Patients and Methods: Twenty-six patients pretreated with gemcitabine-based chemotherapy were enrolled in the study. Docetaxel (75 mg/m², i.v.) was administered every 3 weeks for a maximum of 6 cycles and gefitinib (250 mg/day, p.o.) was given continuously. Results: Five (19.2%) patients achieved stable disease. The median duration of disease control was 4.8 months (range 1–13.2), the median time to disease progression 2.1 months (range 1–7.3) and the median survival time 2.9 months (range 1–13.9). Grade 3/4 neutropenia was recorded in 9 (34.6%) patients, although only 1 (3.8%) developed grade 2 febrile neutropenia. One (3.8%) patient experienced grade 3 fatigue and 2 (7.7%) grade 3 diarrhea. Grade 1/2 rash was observed in 13 (50%) patients. There were no treatment-related deaths. Conclusion: The docetaxel/gefitinib combination, although safe, has no activity as salvage treatment for advanced pancreatic cancer after failure of gemcitabine-based chemotherapy.

Second-Line Capecitabine and Oxaliplatin Combination for Gemcitabine-Resistant Advanced Pancreatic Cancer

“…Several clinical trials have evaluated the safety and efficacy of second-line chemotherapy in this patient population (Klapdor et al, 2000;Mitry et al, 2006;Choi et al, 2014). Guidelines for pancreatic carcinoma currently recommend second-line chemotherapy in selected patients based on the previous publications in which the overall survival is in the range of 3 to 8 months (Demols et al, 2006;Reni et al, 2006;Ignatiadis et al, 2006;Mitry et al, 2006;Boeck et al, 2007;Kulke et al, 2007). Kim et al (2012) analyzed 90 advanced pancreatic adenocarcinoma patients who had received second-line chemotherapy after failure of firstline therapy and they tried to develop a prognostic model to identify patients who would benefit from second-line treatment.…”

“…Gemcitabine is the primary cytotoxic drug in first-line treatment of pancreatic cancer (Burris et al, 1997;Inal et al, 2012). However, chemotherapy options are limited for patients relapsing following firstline gemcitabine-based treatment (Demols et al, 2006;Reni et al, 2006;Ignatiadis et al, 2006;Boeck et al, 2007;Kulke et al, 2007). So, the role of second-line therapy remains controversial (Choi et al, 2014).…”

Metastatic pancreatic cancer: Is gemcitabine still the best standard treatment? (Review)

“…Gefitinib was also evaluated, as a second-line treatment, in combination with docetaxel but the combination failed to be active as a salvage treatment after failure of gemcitabinebased chemotherapy (79).…”

“…Disappointing data came from taxane combination trials: the docetaxel-gefitinib association in a phase II trial demonstrated no activity as a salvage treatment (79).…”

New Targets for Therapy in Pancreatic Cancer

“…Other EGFR tyrosine kinase inhibitors, including gefitinb and lapatinib, have been tested in pilot studies, but failed to demonstrate a clinically significant activity (Brell et al, 2009;Ignatiadis et al, 2006;Safran et al, 2008).…”